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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK65811_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65811_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK65811_"><span class="title" itemprop="name">Carcinoma of Unknown Primary Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: July 8, 2015.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062936__126">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of carcinoma of unknown primary. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062936__127">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062936__1"><h2 id="_CDR0000062936__1_">General Information About Carcinoma of Unknown Primary (CUP)</h2><p id="CDR0000062936__2">The site of origin of a histologically documented carcinoma is not identified
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clinically in approximately 3% of patients; this situation is often referred to
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as CUP origin or occult primary malignancy.[<a class="bk_pop" href="#CDR0000062936_rl_1_1">1</a>-<a class="bk_pop" href="#CDR0000062936_rl_1_6">6</a>]
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</p><div id="CDR0000062936__117"><h3>Prognosis and Survival</h3><p id="CDR0000062936__3">The definition of a CUP varies from study to study; however, at a minimum, this
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determination should include a biopsy of the tumor and a thorough history and
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complete physical examination that includes head and neck, rectal, pelvic, and
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breast examinations; chest x-rays; a complete blood cell count; urinalysis; and
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an examination of the stool for occult blood. The value of other radiographic
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tests will be discussed in the stage information section. When these results
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do not reveal signs of a potential primary lesion and the biopsy is not
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consistent with a primary tumor at the biopsy site, a CUP must be assumed. The
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majority of CUP are adenocarcinomas or undifferentiated tumors; less commonly,
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squamous cell carcinoma, melanoma, sarcoma, and neuroendocrine tumors can also
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present with a primary site of origin that cannot be determined. In approximately 15% to 25% of patients, the primary site cannot be identified even at postmortem examination.[<a class="bk_pop" href="#CDR0000062936_rl_1_7">7</a>]
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</p><p id="CDR0000062936__4">The prognosis for patients with CUP is poor. As a group, the median survival
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is approximately 3 to 4 months with less than 25% and 10% of
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patients alive at 1 and 5 years, respectively. CUP is represented by a
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heterogeneous group of diseases all of which have presented with metastasis as
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the primary manifestation. Although the majority of diseases are relatively
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refractory to systemic treatments, certain clinical presentations of
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CUP carry a much better prognosis. In each instance, distinct
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clinical and pathologic details require consideration for appropriate,
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potentially curative, management.[<a class="bk_pop" href="#CDR0000062936_rl_1_7">7</a>-<a class="bk_pop" href="#CDR0000062936_rl_1_10">10</a>]
|
|
</p><p id="CDR0000062936__5">A retrospective review of 657 consecutive patients with CUP (270 additional
|
|
patients were excluded as a result of identification of a primary malignancy, a
|
|
noncarcinoma cell type, or no malignancy) reported several variables of
|
|
significant prognostic importance identified by multivariate analysis.[<a class="bk_pop" href="#CDR0000062936_rl_1_11">11</a>] Lymph
|
|
node involvement and neuroendocrine histology were associated with longer
|
|
survival; male sex, increasing number of involved organ sites, adenocarcinoma
|
|
histology, and hepatic involvement were unfavorable prognostic factors.
|
|
Adrenal involvement has also been noted to be a poor prognostic finding.[<a class="bk_pop" href="#CDR0000062936_rl_1_12">12</a>]
|
|
</p></div><div id="CDR0000062936__118"><h3>Diagnosis and Patterns of Metastases</h3><p id="CDR0000062936__6">Conceptually, CUP represents a tumor that has a greater propensity for early dissemination than the more common presentation in which
|
|
the primary tumor is apparent with or without metastasis.
|
|
</p><p id="CDR0000062936__7">The distribution of primary sites that are likely to result in CUP contrasts
|
|
with the distribution of major primary adenocarcinomas as reported in the Surveillance, Epidemiology, and End Results data. Most large studies have shown that
|
|
carcinoma of the lung and pancreas are the most common primary carcinomas that
|
|
initially present as CUP. Other common malignancies such as colorectal,
|
|
breast, and prostate cancers infrequently present as CUP.[<a class="bk_pop" href="#CDR0000062936_rl_1_7">7</a>-<a class="bk_pop" href="#CDR0000062936_rl_1_10">10</a>]
|
|
</p><p id="CDR0000062936__8">The pattern of spread of CUP at diagnosis can provide clues to the likelihood
|
|
of the primary site being above or below the diaphragm. Lung metastases are
|
|
twice as common in primary sites ultimately found to be above the diaphragm.
|
|
Liver metastases are more common from primary disease below the diaphragm. The
|
|
pattern of metastasis from a carcinoma presenting as CUP may be significantly
|
|
different from that which would be expected from the usual presentation. For
|
|
instance, bone metastases are approximately three times more common in pancreatic
|
|
cancer that presents as CUP, while osseous metastasis from lung cancer is about 10
|
|
times less common when it presents as CUP, compared with the usual presentation.
|
|
The biologic bases for these differences in presentation, incidence, and
|
|
pattern of metastases are unknown.[<a class="bk_pop" href="#CDR0000062936_rl_1_7">7</a>]
|
|
</p><p id="CDR0000062936__9">Although only a minority of patients will have curable disease or a disease for
|
|
which there is substantial palliative benefit, the appropriate use of special
|
|
diagnostic pathology and selected radiologic studies will identify patients for whom directed therapy will provide the best possible chance for response.
|
|
</p></div><div id="CDR0000062936_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062936_rl_1_1">Pavlidis N, Briasoulis E, Hainsworth J, et al.: Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 39 (14): 1990-2005, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12957453" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12957453</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_2">McCredie M, Coates M, Churches T, et al.: Cancer incidence in New South Wales, Australia. Eur J Cancer 27 (7): 928-31, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1834131" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1834131</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_3">Muir C, Weiland L: Upper aerodigestive tract cancers. Cancer 75 (1 Suppl): 147-53, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/8000993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8000993</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_4">Parkin DM, Whelan SL, Ferlay J, et al., eds.: Cancer Incidence in Five Continents. Volume VII. Lyon, France: International Agency for Research on Cancer, 1997.</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_5">Briasoulis E, Pavlidis N: Cancer of Unknown Primary Origin. Oncologist 2 (3): 142-152, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/10388044" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10388044</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_6">Hainsworth JD, Greco FA: Treatment of patients with cancer of an unknown primary site. N Engl J Med 329 (4): 257-63, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8316270" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8316270</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_7">Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: nonsquamous cell type. Semin Oncol 9 (4): 427-34, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7170628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7170628</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_8">Moertel CG, Reitemeier RJ, Schutt AJ, et al.: Treatment of the patient with adenocarcinoma of unknown origin. Cancer 30 (6): 1469-72, 1972. [<a href="https://pubmed.ncbi.nlm.nih.gov/4641758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4641758</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_9">Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 57 (1): 120-4, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3940611" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3940611</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_10">Ringenberg QS: Tumors of unknown origin. Med Pediatr Oncol 13 (5): 301-6, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/4033541" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4033541</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_11">Abbruzzese JL, Abbruzzese MC, Hess KR, et al.: Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 12 (6): 1272-80, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8201389" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8201389</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_1_12">Hess KR, Abbruzzese MC, Lenzi R, et al.: Classification and regression tree analysis of 1000 consecutive patients with unknown primary carcinoma. Clin Cancer Res 5 (11): 3403-10, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10589751" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10589751</span></a>]</div></li></ol></div></div><div id="CDR0000062936__10"><h2 id="_CDR0000062936__10_">Cellular Classification of CUP </h2><p id="CDR0000062936__11">The pathologist has a central role in the evaluation of carcinoma of unknown
|
|
primary (CUP). A thorough evaluation of an adequate specimen for
|
|
histologic, immunohistochemical, and, when appropriate, electron microscopic
|
|
evaluations is probably the most important clue in the diagnostic
|
|
puzzle of CUP. Pathologic evaluations provide guidance for an appropriate clinical
|
|
evaluation. An obvious corollary to the pathologist’s role is the critical
|
|
interaction between the pathologist, oncologist, and primary physician.[<a class="bk_pop" href="#CDR0000062936_rl_10_1">1</a>]
|
|
</p><p id="CDR0000062936__12">The complexity of the pathologic evaluation tends to be inversely related to
|
|
the degree of differentiation of the tumor. For well- or moderately differentiated tumors, the pathologic diagnosis of an epithelial cancer versus
|
|
lymphoma, sarcoma, melanoma, or a germ cell tumor, for instance, is often
|
|
readily apparent. Commonly used histologic stains such as mucicarmine or
|
|
diastase-sensitive Periodic Acid Schiff can be important in confirming the
|
|
diagnosis of certain tumors of gastrointestinal or renal origin.
|
|
</p><p id="CDR0000062936__13">Special studies can help in distinguishing tumors that are poorly differentiated;[<a class="bk_pop" href="#CDR0000062936_rl_10_2">2</a>,<a class="bk_pop" href="#CDR0000062936_rl_10_3">3</a>] the generic distinction between a poorly differentiated
|
|
tumor of epithelial, hematopoietic, or neuroectodermal origin (i.e., melanoma)
|
|
is important. Microsatellite analysis has been used to assess genetic
|
|
alterations in cervical lymph nodes. These alterations were identical in 18 patients with normal mucosal histology and malignant nodes,
|
|
suggesting a site of primary tumor origin.[<a class="bk_pop" href="#CDR0000062936_rl_10_4">4</a>]
|
|
</p><p id="CDR0000062936__14">Other diagnostic tests:
|
|
</p><ul id="CDR0000062936__72"><li class="half_rhythm"><div class="half_rhythm"><b>Immunohistochemical analysis:</b> Several studies can be important in making these broad distinctions; in
|
|
particular, studies that evaluate staining for keratins, leukocyte common
|
|
antigen, and S-100, a neuroectodermal antigen expressed in melanomas.[<a class="bk_pop" href="#CDR0000062936_rl_10_5">5</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Gene expression profiling:</b> Gene expression profiling using an immunohistochemical panel may allow identification of a potential site of origin in patients with adenocarcinoma of unknown origin. One study reported identification of a potential primary site in 14 of 22 patients.[<a class="bk_pop" href="#CDR0000062936_rl_10_6">6</a>] This modality has not been validated against the gold standard and has not been studied prospectively.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Prostate-specific antigen (PSA) analysis:</b> This histochemical study can accurately differentiate tumors of prostatic
|
|
origin from other types of cancer. Prostate cancer is most often found by digital rectal examination. Approximately
|
|
3% of CUPs are ultimately shown to be prostate cancer. These cancers, as
|
|
mentioned above, appear to have a different metastatic distribution than the
|
|
predominant bony distribution that is generally encountered in prostate cancer.
|
|
When the primary disease may be suspected to have arisen from
|
|
the prostate, prostate cancer-specific tests should be performed to rule out a diagnosis of primary prostate cancer.[<a class="bk_pop" href="#CDR0000062936_rl_10_7">7</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) analysis:
|
|
</b>Immunohistochemical stains are available for both of these proteins. Although
|
|
neither protein is absolutely specific for germ cell tumors, and AFP is not specific for hepatoma, they are important because germ cell tumors are effectively treated with
|
|
combination chemotherapy; appropriate therapy may lead to cure.[<a class="bk_pop" href="#CDR0000062936_rl_10_8">8</a>] The finding of germ cell tumors by genetic
|
|
analysis has been associated with a high response rate to cisplatin therapy,
|
|
thus suggesting that molecular or cytogenetic studies may be useful in
|
|
identifying undifferentiated tumors that are otherwise unclassifiable.[<a class="bk_pop" href="#CDR0000062936_rl_10_9">9</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Polymerase chain reaction (PCR) analysis:</b> In patients with suspected nasopharyngeal carcinoma, DNA amplification of
|
|
Epstein-Barr virus (EBV) genomes can be used for diagnosis with tissue provided
|
|
by fine-needle aspiration biopsy. The presence of EBV in metastases from an
|
|
occult primary tumor suggests the development of overt nasopharyngeal
|
|
carcinoma.[<a class="bk_pop" href="#CDR0000062936_rl_10_10">10</a>] A single study has shown that the i(12p) marker chromosome may
|
|
be used as a diagnostic tool in patients with suspected midline germ cell
|
|
tumors.[<a class="bk_pop" href="#CDR0000062936_rl_10_11">11</a>]</div><div class="half_rhythm">Another study used a molecular assay to evaluate ten tissue type–specific gene markers, using quantitative reverse transcriptase PCR technology to detect tumors originating from the lung, breast, colon, ovary, pancreas, and prostate. About 60% of patients had the putative site of origin identified, thus allowing for administration of treatment-specific therapy.[<a class="bk_pop" href="#CDR0000062936_rl_10_12">12</a>,<a class="bk_pop" href="#CDR0000062936_rl_10_13">13</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Electron microscopic analysis:</b> Electron microscopy (EM) evaluation can sometimes aid in the diagnosis of CUP.
|
|
In particular, the presence of desmosomes and bundles of tonofilaments are
|
|
characteristic of squamous cell cancers. The presence of core granules that
|
|
are diagnostic of neuroendocrine origin is seen in poorly differentiated
|
|
neuroendocrine tumors of unknown primary site.[<a class="bk_pop" href="#CDR0000062936_rl_10_14">14</a>]
|
|
</div><div class="half_rhythm">Acinar spaces and microacinic spaces are seen with adenocarcinomas. Electron
|
|
dense secretory granules are seen in tumors of neuroectodermal origin.
|
|
Premelanosomes can be found in most amelanotic melanomas.
|
|
</div><div class="half_rhythm">The features mentioned above are generally associated with differentiation
|
|
along a particular line. Often poorly differentiated tumors do not display
|
|
such characteristics, making the EM evaluation of little value. It is
|
|
estimated that EM may aid in distinguishing a primary diagnosis that has not
|
|
been obtained by light microscopy approximately 10% of the time.[<a class="bk_pop" href="#CDR0000062936_rl_10_15">15</a>-<a class="bk_pop" href="#CDR0000062936_rl_10_17">17</a>]
|
|
Because of the development of immunohistochemical stains, EM is rarely needed.</div></li></ul><div id="CDR0000062936_rl_10"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062936_rl_10_1">Haskell CM, Cochran AJ, Barsky SH, et al.: Metastasis of unknown origin. Curr Probl Cancer 12 (1): 5-58, 1988 Jan-Feb. [<a href="https://pubmed.ncbi.nlm.nih.gov/3067982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3067982</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_2">Ruddon RW, Norton SE: Use of biological markers in the diagnosis of cancers of unknown primary tumor. Semin Oncol 20 (3): 251-60, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8503021" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8503021</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_3">Mackay B, Ordonez NG: Pathological evaluation of neoplasms with unknown primary tumor site. Semin Oncol 20 (3): 206-28, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8503017" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8503017</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_4">Califano J, Westra WH, Koch W, et al.: Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst 91 (7): 599-604, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10203278" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10203278</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_5">Battifora H: Recent progress in the immunohistochemistry of solid tumors. Semin Diagn Pathol 1 (4): 251-71, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6400635" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6400635</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_6">Horlings HM, van Laar RK, Kerst JM, et al.: Gene expression profiling to identify the histogenetic origin of metastatic adenocarcinomas of unknown primary. J Clin Oncol 26 (27): 4435-41, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18802156" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18802156</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_7">Yam LT, Winkler CF, Janckila AJ, et al.: Prostatic cancer presenting as metastatic adenocarcinoma of undetermined origin. Immunodiagnosis by prostatic acid phosphatase. Cancer 51 (2): 283-7, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6336978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6336978</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_8">Greco FA, Hainsworth JD: Cancer of unknown primary site. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 2033-51.</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_9">Motzer RJ, Rodriguez E, Reuter VE, et al.: Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. J Clin Oncol 13 (1): 274-82, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7799031" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7799031</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_10">Feinmesser R, Miyazaki I, Cheung R, et al.: Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. N Engl J Med 326 (1): 17-21, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1309196" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1309196</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_11">Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8308927" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8308927</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_12">Varadhachary GR, Talantov D, Raber MN, et al.: Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol 26 (27): 4442-8, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18802157" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18802157</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_13">Hainsworth JD, Rubin MS, Spigel DR, et al.: Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol 31 (2): 217-23, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23032625" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23032625</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_14">Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity. Ann Intern Med 109 (5): 364-71, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/2841895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2841895</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_15">Hanna W, Kahn HJ: The ultrastructure of metastatic adenocarcinoma in serous fluids. An aid in identification of the primary site of the neoplasm. Acta Cytol 29 (3): 202-10, 1985 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/3859120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3859120</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_16">Herrera GA, Reimann BE: Electron microscopy in determining origin of metastatic adenocarcinomas. South Med J 77 (12): 1557-66, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6505766" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6505766</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_10_17">Mackay B, Ordonez NG: The role of the pathologist in the evaluation of poorly differentiated tumors. Semin Oncol 9 (4): 396-415, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/6763334" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6763334</span></a>]</div></li></ol></div></div><div id="CDR0000062936__26"><h2 id="_CDR0000062936__26_">Stage Information for CUP </h2><p id="CDR0000062936__27">Opinions are divergent concerning the value and extent of evaluation that
|
|
should be performed to determine the primary tumor in patients who present with
|
|
carcinoma of unknown primary (CUP). Clinical and pathological investigations
|
|
to detect tumors that are potentially responsive to treatment (e.g., lymphoma,
|
|
germ cell tumor, breast, or ovarian tumor) may be undertaken.
|
|
</p><p id="CDR0000062936__28">The chest radiograph has become an almost routine procedure in general medical
|
|
practice. Although chest radiography is routinely performed, in the setting of
|
|
CUP no distinguishing feature clearly separates primary from
|
|
metastatic disease within the chest. The abdominal computed tomographic (CT)
|
|
scan is the only radiographic test that may frequently be of value in defining
|
|
the primary site, because of the
|
|
inordinately high representation of pancreatic cancer in the CUP process.[<a class="bk_pop" href="#CDR0000062936_rl_26_1">1</a>]
|
|
With the exception of ovarian cancer, however, CT scans rarely identify
|
|
treatable primary cancers.[<a class="bk_pop" href="#CDR0000062936_rl_26_2">2</a>,<a class="bk_pop" href="#CDR0000062936_rl_26_3">3</a>]
|
|
</p><p id="CDR0000062936__29">The clinical biology of the disease, the types of tumors most often
|
|
encountered, and the high level of inaccuracy of unguided radiographic studies
|
|
raise issues of cost effectiveness for intensive diagnostic work-up. Two
|
|
studies have indicated that a large negative cost/benefit ratio exists for an
|
|
extensive unguided clinical evaluation, with a single study citing a 9.5%
|
|
increase in 1-year survival at a cost of 2 to 8 million dollars. The most
|
|
reasonable approach is to develop a comprehensive knowledge of the manner in
|
|
which CUP patients present and to remember that this presentation is associated
|
|
with tremendous heterogeneity regarding outcome.[<a class="bk_pop" href="#CDR0000062936_rl_26_4">4</a>-<a class="bk_pop" href="#CDR0000062936_rl_26_9">9</a>]
|
|
</p><div id="CDR0000062936__73"><h3>Cervical Lymph Nodes</h3><p id="CDR0000062936__31">A histologic diagnosis of metastatic carcinoma in cervical nodes requires a
|
|
meticulous examination of the upper aerorespiratory tract. Histologically,
|
|
these tumors are usually squamous cell carcinoma, but occasionally may be adenocarcinoma, melanoma, or anaplastic
|
|
tumors. Metastatic adenocarcinoma is generally associated with a poor
|
|
prognosis. Approximately 2% to 5% of patients with primary squamous cell
|
|
carcinoma of the head and neck region will present with cervical adenopathy as
|
|
the primary disease manifestation; about 10% of this group will present with
|
|
bilateral adenopathy. The 3-year survival rate ranges from 35% to 59% when
|
|
patients with squamous or undifferentiated tumors are treated with radical
|
|
radiation therapy, surgery, or both.[<a class="bk_pop" href="#CDR0000062936_rl_26_10">10</a>-<a class="bk_pop" href="#CDR0000062936_rl_26_12">12</a>]
|
|
</p></div><div id="CDR0000062936__74"><h3>Poorly Differentiated Carcinomas</h3><p id="CDR0000062936__33">Investigators have defined a subpopulation of potentially curable patients with
|
|
1 or more of the following characteristics:
|
|
</p><ul id="CDR0000062936__34"><li class="half_rhythm"><div>Age younger than 50 years.
|
|
</div></li><li class="half_rhythm"><div>Midline tumor distribution, multiple pulmonary nodules or lymph nodes,
|
|
elevated serum levels of beta human chorionic gonadotropins (HCG) or
|
|
alpha-fetoprotein (AFP).
|
|
</div></li><li class="half_rhythm"><div>Cells positive for beta HCG or AFP by immunohistochemical stain.
|
|
</div></li><li class="half_rhythm"><div>The presence of neuroendocrine granules.
|
|
</div></li><li class="half_rhythm"><div>Clinical evidence for rapid tumor growth.
|
|
</div></li><li class="half_rhythm"><div>Tumors that were very responsive to chemotherapy or radiation therapy.</div></li></ul><p id="CDR0000062936__35">In retrospective review, many of these patients, including some complete
|
|
responders to chemotherapy, did not have any recognizable histopathologic
|
|
features of germ cell tumors.[<a class="bk_pop" href="#CDR0000062936_rl_26_13">13</a>-<a class="bk_pop" href="#CDR0000062936_rl_26_15">15</a>] A single study has shown that the i(12p)
|
|
marker chromosome may be used as a diagnostic tool in patients with suspected
|
|
midline germ cell tumors.[<a class="bk_pop" href="#CDR0000062936_rl_26_16">16</a>]
|
|
</p></div><div id="CDR0000062936__75"><h3>Metastatic Melanoma to a Single Nodal Site</h3><p id="CDR0000062936__37">Approximately 5% of patients with malignant melanoma will present without a
|
|
documented primary site. Special stains and electron microscopy
|
|
may be important in establishing the diagnosis. Patients with this diagnosis
|
|
should, like those with stage II melanoma, have a radical lymph node
|
|
dissection. Survival is actually slightly better than that seen in patients with stage II
|
|
melanoma with a documented primary site.[<a class="bk_pop" href="#CDR0000062936_rl_26_5">5</a>,<a class="bk_pop" href="#CDR0000062936_rl_26_17">17</a>-<a class="bk_pop" href="#CDR0000062936_rl_26_19">19</a>] (Refer to the PDQ summary on
|
|
<a href="/books/n/pdqcis/CDR0000062917/">Melanoma Treatment</a> for more information.)
|
|
</p></div><div id="CDR0000062936__76"><h3>Isolated Axillary Metastasis</h3><p id="CDR0000062936__39">Most patients who present with nodal metastasis above the diaphragm ultimately
|
|
are documented to have lung cancer, the most common supradiaphragmatic primary
|
|
malignancy. The presence of isolated axillary metastasis in females, however,
|
|
raises another possibility. A few studies involving a small number of patients
|
|
have shown that approximately 50% of patients who present with isolated
|
|
axillary metastasis of an adenocarcinoma will ultimately be shown to have
|
|
breast cancer. Although some of these patients will have a positive mammogram
|
|
after the initial evaluation, approximately 50% of the patients will not.
|
|
When these patients are treated with local excision, or as having primary
|
|
breast cancer, 2- to 10-year survival has been obtained in approximately 50% of
|
|
patients. The availability of estrogen-receptor (ER) and progesterone-receptor
|
|
(PR) assays may aid in this diagnosis, and these studies should be performed in
|
|
this setting. If the clinical setting is consistent with breast cancer, and ER
|
|
and/or PR levels are elevated, CUP with this distribution should be treated as
|
|
breast cancer.[<a class="bk_pop" href="#CDR0000062936_rl_26_1">1</a>,<a class="bk_pop" href="#CDR0000062936_rl_26_4">4</a>,<a class="bk_pop" href="#CDR0000062936_rl_26_20">20</a>] (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062787/">Breast Cancer Treatment</a> for more
|
|
information.)
|
|
</p></div><div id="CDR0000062936__77"><h3>Inguinal Node Metastasis</h3><p id="CDR0000062936__41">Squamous carcinoma detected in the inguinal lymph nodes is almost always
|
|
metastatic from the genital or anal/rectal area. In females, careful
|
|
examination of the vulva, vagina, and cervix is indicated, with biopsy of any
|
|
suspicious areas. The penis of uncircumcised males should be carefully
|
|
inspected. In both sexes, the anorectal area should be carefully examined,
|
|
including biopsy of suspicious areas. Isolated metastases present in the
|
|
central nervous system, the liver, and the genitourinary tract. Information
|
|
about these presentations may be found in PDQ summaries that specifically
|
|
detail their management.
|
|
</p><p id="CDR0000062936__42">In addition to the above situations, significant palliation can be achieved in certain instances in patients with CUP. Breast, prostate,
|
|
ovarian, and thyroid cancers are all treatable malignancies, even when
|
|
metastatic, and they represent approximately 15% of all CUP tumors. As with
|
|
other CUP presentations, the pattern of spread of these malignancies is
|
|
somewhat atypical. For instance, patients with prostate cancer who present
|
|
with CUP have an inordinately high incidence of metastases to nonosseous sites
|
|
such as lung (75%), liver (50%), and brain (25%). Bone metastases are also
|
|
less common than lung metastases in thyroid cancer presenting as CUP.
|
|
</p></div><div id="CDR0000062936_rl_26"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062936_rl_26_1">Copeland EM, McBride CM: Axillary metastases from unknown primary sites. Ann Surg 178 (1): 25-7, 1973. [<a href="/pmc/articles/PMC1355857/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1355857</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/4352233" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4352233</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_2">Abbruzzese JL, Abbruzzese MC, Lenzi R, et al.: Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol 13 (8): 2094-103, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7636553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7636553</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_3">Karsell PR, Sheedy PF 2nd, O'Connell MJ: Computed tomography in search of cancer of unknown origin. JAMA 248 (3): 340-3, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7087129" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7087129</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_4">Patel J, Nemoto T, Rosner D, et al.: Axillary lymph node metastasis from an occult breast cancer. Cancer 47 (12): 2923-7, 1981. [<a href="https://pubmed.ncbi.nlm.nih.gov/7260879" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7260879</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_5">Klausner JM, Gutman M, Inbar M, et al.: Unknown primary melanoma. J Surg Oncol 24 (2): 129-31, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6632893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6632893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_6">Schapira DV, Jarrett AR: The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma. Arch Intern Med 155 (19): 2050-4, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7575063" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7575063</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_7">Levine MN, Drummond MF, Labelle RJ: Cost-effectiveness in the diagnosis and treatment of carcinoma of unknown primary origin. CMAJ 133 (10): 977-87, 1985. [<a href="/pmc/articles/PMC1346409/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1346409</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/3933808" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3933808</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_8">Maisey MN, Ellam SV: Investigating the adenocarcinoma of unknown origin (ACUP): a cost benefit analysis. Rev Epidemiol Sante Publique 32 (1): 57-61, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6718798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6718798</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_9">Schwartz SC, Klein J, Peters WP: Carcinoma of unknown primary site. In: Stein JH, ed.: Internal Medicine. St. Louis, Mo: Mosby, 1998, pp 729-733.</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_10">DeSanto LW, Neel HB 3rd: Squamous cell carcinoma. Metastasis to the neck from an unknown or undiscovered primary. Otolaryngol Clin North Am 18 (3): 505-13, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/2995900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2995900</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_11">Muraki AS, Mancuso AA, Harnsberger HR: Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology 152 (3): 749-53, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6463256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6463256</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_12">Silverman C, Marks JE: Metastatic cancer of unknown origin: epidermoid and undifferentiated carcinomas. Semin Oncol 9 (4): 435-41, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7170629" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7170629</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_13">Greco FA, Vaughn WK, Hainsworth JD: Advanced poorly differentiated carcinoma of unknown primary site: recognition of a treatable syndrome. Ann Intern Med 104 (4): 547-53, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3006571" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3006571</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_14">Hainsworth JD, Wright EP, Gray GF Jr, et al.: Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy. J Clin Oncol 5 (8): 1275-80, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/2442318" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2442318</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_15">Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity. Ann Intern Med 109 (5): 364-71, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/2841895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2841895</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_16">Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8308927" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8308927</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_17">Panagopoulos E, Murray D: Metastatic malignant melanoma of unknown primary origin: a study of 30 cases. J Surg Oncol 23 (1): 8-10, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6843134" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6843134</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_18">Reintgen DS, McCarty KS, Woodard B, et al.: Metastatic malignant melanoma with an unknown primary. Surg Gynecol Obstet 156 (3): 335-40, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6828979" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6828979</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_19">Giuliano AE, Cochran AJ, Morton DL: Melanoma from unknown primary site and amelanotic melanoma. Semin Oncol 9 (4): 442-7, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/7170630" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7170630</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_26_20">Merson M, Andreola S, Galimberti V, et al.: Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer 70 (2): 504-8, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1617600" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1617600</span></a>]</div></li></ol></div></div><div id="CDR0000062936__43"><h2 id="_CDR0000062936__43_">Newly Diagnosed CUP</h2><p id="CDR0000062936__44">The overwhelming majority of patients presenting with carcinoma of unknown
|
|
primary (CUP) have disseminated disease that is relatively chemoresistant.
|
|
Potentially curative treatment can
|
|
be delivered, however, in a few situations.
|
|
</p><div id="CDR0000062936__45"><h3>Cervical Lymph Nodes</h3><p id="CDR0000062936__46">All patients should undergo a careful head, neck, and lung evaluation including
|
|
coronal computed tomography and/or magnetic resonance imaging of the
|
|
head and neck and directed biopsies of the nasopharynx and tongue base. In
|
|
those patients with squamous cell or undifferentiated carcinoma,
|
|
tonsillectomies have been recommended and should be considered if the tonsils
|
|
have not been previously removed.[<a class="bk_pop" href="#CDR0000062936_rl_43_1">1</a>] Fluorodeoxyglucose F 18-positron emission tomography scan may identify an occult primary site in the head and neck area.[<a class="bk_pop" href="#CDR0000062936_rl_43_2">2</a>,<a class="bk_pop" href="#CDR0000062936_rl_43_3">3</a>] If no primary site can be determined, the
|
|
following approaches should be considered:
|
|
</p><ul id="CDR0000062936__47"><li class="half_rhythm"><div>Radical radiation therapy with curative intent to the cervical lymph nodes
|
|
and possible sites of origin.[<a class="bk_pop" href="#CDR0000062936_rl_43_4">4</a>] Intensity-modulated radiation therapy (IMRT) may have less short- and long-term toxicity than conventional radiation therapy in terms of xerostomia, acute dysphagia, and skin fibrosis.[<a class="bk_pop" href="#CDR0000062936_rl_43_5">5</a>-<a class="bk_pop" href="#CDR0000062936_rl_43_7">7</a>]</div></li><li class="half_rhythm"><div>Preoperative radiation therapy followed by radical neck dissection.
|
|
</div></li><li class="half_rhythm"><div>Radical neck dissection.
|
|
</div></li><li class="half_rhythm"><div>Radical neck dissection followed by postoperative radiation therapy to
|
|
possible sites of origin.[<a class="bk_pop" href="#CDR0000062936_rl_43_8">8</a>]
|
|
</div></li></ul><p id="CDR0000062936__48">(Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062919/">Metastatic Squamous Neck Cancer with Occult
|
|
Primary Cancer Treatment</a> for more information.)
|
|
</p></div><div id="CDR0000062936__49"><h3>Poorly Differentiated Carcinomas</h3><p id="CDR0000062936__50">Patients who have poorly differentiated carcinomas with or without serologic or
|
|
histologic evidence of beta human chorionic gonadotropins or alpha-fetoprotein
|
|
should be treated with intensive chemotherapy as used in the treatment of
|
|
disseminated germ cell tumors.
|
|
</p><p id="CDR0000062936__51">In a series, more than 220 patients with excellent performance status were
|
|
treated with aggressive combination chemotherapy. This chemotherapy generally
|
|
consisted of vinblastine, bleomycin, and cisplatin; however, some patients
|
|
received a doxorubicin-containing modification of this regimen and some
|
|
received etoposide instead of vinblastine. The response rate was 63%, with a
|
|
complete response rate of 26%, and a long-term disease-free survival of 16%.[<a class="bk_pop" href="#CDR0000062936_rl_43_9">9</a>]
|
|
Carboplatin-containing regimens were found to have equal activity.[<a class="bk_pop" href="#CDR0000062936_rl_43_10">10</a>] A
|
|
paclitaxel-based combination yielded a 48% response rate in 71 patients with
|
|
various histologic types of carcinoma of unknown origin.[<a class="bk_pop" href="#CDR0000062936_rl_43_11">11</a>]
|
|
</p></div><div id="CDR0000062936__52"><h3>Poorly Differentiated Neuroendocrine Carcinomas</h3><p id="CDR0000062936__53">In a series of 29 patients with poorly differentiated neuroendocrine carcinomas, 19 were treated with intensive cisplatin-based
|
|
combination chemotherapy, and six additional patients received doxorubicin
|
|
combinations. Six patients achieved complete response and four of these patients
|
|
were alive 19 to 100 months after diagnosis.[<a class="bk_pop" href="#CDR0000062936_rl_43_12">12</a>]
|
|
</p></div><div id="CDR0000062936__54"><h3>Peritoneal Carcinomatosis</h3><p id="CDR0000062936__55">Women with peritoneal carcinomatosis of an adenocarcinoma
|
|
serous histologic type have a favorable response to chemotherapy and improved prognosis. Response and survival rates in these patients approach
|
|
those seen in ovarian cancer patients, and therapy appropriate for ovarian
|
|
cancer should be used.[<a class="bk_pop" href="#CDR0000062936_rl_43_13">13</a>,<a class="bk_pop" href="#CDR0000062936_rl_43_14">14</a>] (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062829/">Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment</a> for more information.)
|
|
</p></div><div id="CDR0000062936__56"><h3>Isolated Axillary-Nodal Metastasis</h3><p id="CDR0000062936__57">The most common primary site for isolated axillary metastasis is the breast. Mammography should be
|
|
performed in all patients with isolated axillary-nodal metastasis. After an
|
|
adequate evaluation of the breast and lung to rule out these primary sites, the
|
|
following treatment options should be considered:
|
|
</p><ul id="CDR0000062936__58"><li class="half_rhythm"><div>Lymph node dissection with or without mastectomy or radiation therapy to
|
|
the breast with curative intent.[<a class="bk_pop" href="#CDR0000062936_rl_43_15">15</a>]
|
|
</div></li><li class="half_rhythm"><div>Lymph node dissection with or without mastectomy or radiation therapy to
|
|
the breast with curative intent plus adjuvant chemotherapy with an accepted
|
|
therapeutic adjuvant approach for breast cancer. This option should be
|
|
considered especially if breast cancer is proven or if other lymph nodes
|
|
show adenocarcinoma.[<a class="bk_pop" href="#CDR0000062936_rl_43_16">16</a>]
|
|
</div></li></ul></div><div id="CDR0000062936__59"><h3>Inguinal Node Metastasis</h3><p id="CDR0000062936__60">Metastatic carcinoma in inguinal nodes from an unknown primary source occurs in
|
|
approximately 1% to 3.5% of patients. A diagnostic excisional-node biopsy
|
|
should be performed when no primary source of carcinoma can be found. The most
|
|
common pathologic diagnosis in this instance is Hodgkin lymphoma or
|
|
non-Hodgkin lymphoma, with CUP being less frequent.
|
|
</p><p id="CDR0000062936__61"><b>Treatment options:</b>
|
|
</p><ul id="CDR0000062936__62"><li class="half_rhythm"><div>Superficial groin dissection alone.
|
|
</div></li><li class="half_rhythm"><div>Local excisional biopsy with or without radiation, inguinal node
|
|
dissection, or chemotherapy.
|
|
</div></li></ul><p id="CDR0000062936__63">In a small proportion of patients, local excision alone is sufficient therapy.
|
|
Initial therapy with radiation may be used successfully in some patients,
|
|
depending on extent of disease and individual patient characteristics.
|
|
Isolated metastases also present in the central nervous system, liver, and
|
|
genitourinary tract.[<a class="bk_pop" href="#CDR0000062936_rl_43_17">17</a>] More information can be found in the PDQ summaries
|
|
for these malignancies.
|
|
</p></div><div id="CDR0000062936__64"><h3>Melanoma (Melanotic or Amelanotic) Occurring in a Single Nodal Site</h3><p id="CDR0000062936__65">Approximately 5% of patients present with no detectable primary site. </p><p id="CDR0000062936__88"><b>Treatment option:</b></p><ul id="CDR0000062936__66"><li class="half_rhythm"><div>Radical lymph node dissection.
|
|
For patients who present with a single site of nodal metastasis, this treatment will yield a survival that is slightly better than that obtained in conventional
|
|
stage II melanoma.
|
|
</div></li></ul></div><div id="CDR0000062936__67"><h3>Multiple Involvement</h3><p id="CDR0000062936__68">When patients present with widespread metastatic disease and special
|
|
studies reveal a probable primary tumor for which standard systemic therapy is
|
|
available, such therapy should be administered. This may include hormonal
|
|
therapy for prostate and breast cancer, I<sup>131</sup> for thyroid cancer, or cytotoxic
|
|
single-agent or combination chemotherapy for hormone-refractory breast and
|
|
ovarian cancers. Standard approaches for such diseases are available in the
|
|
specific PDQ summaries for each diagnosis.
|
|
</p><p id="CDR0000062936__69">The majority of patients will not have a definable primary source. For such
|
|
patients, a variety of combination chemotherapy approaches have been tried with
|
|
little success. No treatment can be considered standard at present.
|
|
Therefore, such patients should be considered for available clinical trials.
|
|
Information about ongoing clinical trials is available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062936__TrialSearch_43_sid_4"><h3>Current Clinical Trials</h3><p id="CDR0000062936__TrialSearch_43_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062936_rl_43"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062936_rl_43_1">Righi PD, Sofferman RA: Screening unilateral tonsillectomy in the unknown primary. Laryngoscope 105 (5 Pt 1): 548-50, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7760677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7760677</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_2">Lassen U, Daugaard G, Eigtved A, et al.: 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT). Eur J Cancer 35 (7): 1076-82, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10533451" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10533451</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_3">Rades D, Kühnel G, Wildfang I, et al.: Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management. Ann Oncol 12 (11): 1605-9, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11822762" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11822762</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_4">Beldì D, Jereczek-Fossa BA, D'Onofrio A, et al.: Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients. Int J Radiat Oncol Biol Phys 69 (4): 1051-8, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17716824" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17716824</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_5">Madani I, Vakaet L, Bonte K, et al.: Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 71 (4): 1158-66, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18258383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18258383</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_6">Sher DJ, Balboni TA, Haddad RI, et al.: Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck. Int J Radiat Oncol Biol Phys 80 (5): 1405-11, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21177045" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21177045</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_7">Villeneuve H, Després P, Fortin B, et al.: Cervical lymph node metastases from unknown primary cancer: a single-institution experience with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 82 (5): 1866-71, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/21497452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21497452</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_8">Davidson BJ, Spiro RH, Patel S, et al.: Cervical metastases of occult origin: the impact of combined modality therapy. Am J Surg 168 (5): 395-9, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7977958" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7977958</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_9">Hainsworth JD, Johnson DH, Greco FA: Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol 10 (6): 912-22, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1375284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1375284</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_10">Pavlidis N, Kosmidis P, Skarlos D, et al.: Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site. A Hellenic Cooperative Oncology Group Study. Ann Oncol 3 (8): 631-4, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1450045" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1450045</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_11">Greco FA, Burris HA 3rd, Erland JB, et al.: Carcinoma of unknown primary site. Cancer 89 (12): 2655-60, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11135228" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11135228</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_12">Garrow GC, Greco FA, Hainsworth JD: Poorly differentiated neuroendocrine carcinoma of unknown primary tumor site. Semin Oncol 20 (3): 287-91, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8503025" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8503025</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_13">Strnad CM, Grosh WW, Baxter J, et al.: Peritoneal carcinomatosis of unknown primary site in women. A distinctive subset of adenocarcinoma. Ann Intern Med 111 (3): 213-7, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2502058" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2502058</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_14">Dalrymple JC, Bannatyne P, Russell P, et al.: Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases. Cancer 64 (1): 110-5, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2731107" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2731107</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_15">Merson M, Andreola S, Galimberti V, et al.: Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer 70 (2): 504-8, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1617600" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1617600</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_16">Ellerbroek N, Holmes F, Singletary E, et al.: Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. Cancer 66 (7): 1461-7, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2207996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2207996</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062936_rl_43_17">Guarischi A, Keane TJ, Elhakim T: Metastatic inguinal nodes from an unknown primary neoplasm. A review of 56 cases. Cancer 59 (3): 572-7, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3791166" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3791166</span></a>]</div></li></ol></div></div><div id="CDR0000062936__70"><h2 id="_CDR0000062936__70_">Recurrent CUP</h2><p id="CDR0000062936__71">The prognosis for any treated cancer patient with progressing, recurring, or
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relapsing disease is poor, regardless of cell type or stage. Deciding on
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further treatment depends on many factors, including the specific cancer, prior
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treatment, and site of recurrence, as well as individual patient
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considerations. Treatments that are under clinical evaluation are appropriate
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and should be considered when possible. Information about ongoing clinical trials is available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>. </p><div id="CDR0000062936__TrialSearch_70_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062936__TrialSearch_70_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div></div><div id="CDR0000062936__80"><h2 id="_CDR0000062936__80_">Changes to This Summary (07/08/2015)</h2><p id="CDR0000062936__81">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.</p><p id="CDR0000062936__125">Editorial changes were made to this summary.</p><p id="CDR0000062936__disclaimerHP_3">This summary is written and maintained by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062936__AboutThis_1">About This PDQ Summary</a> and <a href="http://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® - NCI's Comprehensive Cancer Database</a> pages.
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</p></div><div id="CDR0000062936__AboutThis_1"><h2 id="_CDR0000062936__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062936__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062936__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of carcinoma of unknown primary. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062936__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062936__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062936__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062936__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062936__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p id="CDR0000062936__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062936__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062936__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062936__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062936__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062936__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062936__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Carcinoma of Unknown Primary Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389252]</p><p id="CDR0000062936__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062936__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062936__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062936__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062936__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65811.1/?report=reader">PubReader</a></li><li><a href="/books/NBK65811.1/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65811" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65811" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. Carcinoma of Unknown Primary Treatment (PDQ®): Health Professional Version. 2015 Jul 8. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></div></div></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Version History</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter shutter_closed" title="Show/hide content" remembercollapsed="true" pgsec_name="version_history" id="Shutter"></a></div><div class="portlet_content" style="display: none;"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><span class="bk_col_itm"><a href="/books/NBK65811.5/">NBK65811.5</a></span> May 6, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65811.4/">NBK65811.4</a></span> December 22, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65811.3/">NBK65811.3</a></span> December 8, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65811.2/">NBK65811.2</a></span> February 4, 2018</li><li><span class="bk_col_itm">NBK65811.1</span> July 8, 2015 (Displayed Version)</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#CDR0000062936__1" ref="log$=inpage&link_id=inpage">General Information About Carcinoma of Unknown Primary (CUP)</a></li><li><a href="#CDR0000062936__10" ref="log$=inpage&link_id=inpage">Cellular Classification of CUP </a></li><li><a href="#CDR0000062936__26" ref="log$=inpage&link_id=inpage">Stage Information for CUP </a></li><li><a href="#CDR0000062936__43" ref="log$=inpage&link_id=inpage">Newly Diagnosed CUP</a></li><li><a href="#CDR0000062936__70" ref="log$=inpage&link_id=inpage">Recurrent CUP</a></li><li><a href="#CDR0000062936__80" ref="log$=inpage&link_id=inpage">Changes to This Summary (07/08/2015)</a></li><li><a href="#CDR0000062936__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65797/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" 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class="portlet_content"><ul><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389193" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Nasopharyngeal Carcinoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Nasopharyngeal Carcinoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" 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