[MOL] CUP/ACUP for Alan [00641] Medicine On Line


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[MOL] CUP/ACUP for Alan



http://noah.cuny.edu/cancer/nci/cancernet/103331.html
Unknown Primary - some information sites for Alan

http://www3.cancer.org/cancerinfo/res_home.asp?ct=58

http://www.meb.uni-bonn.de/cancernet/103331.html

http://tirgan.com/unknown.htm

I am so sorry to hear of the loss of your beloved wife. I hope you can
now look into this and find some consolation about this diagnosis.

Yes, it is not good news that the primary remains undetected. If a
primary site can be found, eg colon, ovarian, etc then treatment can
proceed for that primary site. Otherwise, it like shooting bullets into
the dark. I have this diagnosis (Dec 97) with only a talc pluerdesis as
treatment back then. There now newer tests and drugs that might change
the dire outlook for this diagnosis.  God Bless, Jeanne

Some sites for you below. Let us know how you are doing or if you have
questions. We are not medical people though I was trained as an R.N. but
we do give each other emotional and research help. 

http://tirgan.com/unknown.htm
Title: Carcinoma of unknown primary (Physician)
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Ask NOAH About: Cancer


Carcinoma of unknown primary

208/03331

CancerNet: National Cancer Institute

PDQ Information for Health Care Professionals [for patients]


Choose one of the following options to see the information directly:


This information is intended for use by doctors and other health care professionals. If you are a cancer patient, your doctor can explain how it applies to you, or you can call the Cancer Information Service at 1-800-422-6237. CancerNet also contains PDQ information for patients; see the CancerNet Contents List for PDQ for more information.


GENERAL INFORMATION

The site of origin of a histologically documented carcinoma is not identified clinically in approximately 3% of patients; this situation is often referred to as carcinoma of unknown primary (CUP) origin or occult primary malignancy.[1-5]

The definition of a CUP varies from study to study; however, at a minimum, this determination should include a biopsy of the tumor and a thorough history and complete physical examination that includes head and neck, rectal, pelvic, and breast examinations; chest x-rays; a complete blood cell count, urinalysis, and an examination of the stool for occult blood. The value of other radiographic tests will be discussed in the stage information section. When these results do not reveal signs of a potential primary lesion, and the biopsy is not consistent with a primary tumor at the biopsy site, a CUP must be assumed. The majority of CUP are adenocarcinomas or undifferentiated tumors; less commonly, squamous cell carcinoma, melanoma, sarcoma, and neuroendocrine tumors can also present with a primary site of origin that cannot be determined. The most extreme examples occur in the 15% to 25% of patients in whom the diagnosis of the primary site cannot be determined even at postmortem examination.[6]

The prognosis for patients with CUP is poor. As a group, the median survival is approximately 3 to 4 months in most studies with less than 25% and 10% of patients alive at 1 and 5 years, respectively. CUP is represented by a heterogeneous group of diseases all of which have presented with metastasis as the primary manifestation. Although the majority of diseases are relatively refractory to systemic treatments, there are certain clinical presentations of CUP that carry a much better prognosis. In each instance, there are distinct clinical and pathologic details that require consideration for appropriate, potentially curative, management.[6-9]

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. 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.[10]

Conceptually, CUP represents a tumor that has a greater propensity for "early" clinically apparent dissemination than the more common presentation in which the primary tumor is apparent with or without metastases.

The distribution of primary sites that are likely to result in CUP contrasts with the distribution of major primary adenocarcinomas as reported in the SEER (Survival and End Results Program) 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.[6-9]

The pattern of spread of CUP at diagnosis can provide clues to the likelihood of the primary disease 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 3 times more common in pancreatic cancer presenting 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.[6]

Although only a minority of patients will have curable disease or a disease for which there is substantial palliative benefit, the opportunity for treating such patients should not be ignored or lost. This knowledge combined with the appropriate use of special diagnostic pathology and selected radiologic studies will provide the optimal benefit for patients who present with CUP.

References:

  1. McCredie M, Coates M, Churches T, et al.: Cancer incidence in New South Wales, Australia. European Journal of Cancer 27(7): 928-931, 1991.
  2. Muir C: Cancer of unknown primary site. Cancer 75(1): 353-356, 1995.
  3. Parkin DM, Muir CS, Whelan SL, et al., eds.: Cancer Incidence in Five Continents: Volume VI. New York, Ny: Oxford University Press, 1992.
  4. Briasoulis E, Pavlidis N: Cancer of unknown primary origin. The Oncologist 2: 142-152, 1997.
  5. Hainsworth JD, Greco FA: Treatment of patients with cancer of an unknown primary site. New England Journal of Medicine 329(4): 257-263, 1993.
  6. Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: nonsquamous cell type. Seminars in Oncology 9(4): 427-434, 1982.
  7. Moertel CG, Reitemeier RJ, Schutt AJ, et al.: Treatment of the patient with adenocarcinoma of unknown origin. Cancer 30(6): 1469-1472, 1972.
  8. Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 57(1): 120-124, 1986.
  9. Ringenberg QS: Tumors of unknown origin. Medical and Pediatric Oncology 13(5): 301-306, 1985.
  10. Abbruzzese JL, Abbruzzese MC, Hess KR, et al.: Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. Journal of Clinical Oncology 12(6): 1272-1280, 1994.


CELLULAR CLASSIFICATION

The pathologist has a central role in the evaluation of carcinoma of unknown primary (CUP). There is probably no more important clue to the diagnostic puzzle of CUP than a thorough evaluation of an adequate specimen for histologic, immunohistochemical, and, when appropriate, electron microscopic evaluations. These evaluations provide guidance for the appropriate clinical evaluation that ensues. An obvious corollary to the pathologist's role is the critical interaction between the pathologist, oncologist, and primary physician.[1]

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 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.

Special studies can help in distinguishing more poorly differentiated tumors.[2,3] Often, the generic distinction between a poorly differentiated tumor of epithelial, hematopoietic, or neuroectodermal origin (i.e., melanoma) is of importance.

Immunohistochemical: 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.[4]

Prostate specific antigen (PSA): This histochemical study can accurately differentiate tumors of prostatic origin from other types of cancer. Most often prostate cancer is found as an obvious prostatic cancer by digital rectal examination. However, approximately 3% of CUPs are ultimately shown to be prostatic 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. Thus, when there is any suspicion that the primary disease may have arisen from the prostate, the specificity of the test and the availability of relatively nontoxic hormonal approaches emphasize the need to evaluate this diagnostic possibility in the CUP setting.[5]

Human chorionic gonadotropins (HCG) and alpha-fetoprotein (AFP): Immunohistochemical stains are available for both of these proteins. Although neither is absolutely specific for germ cell tumors (HCG and AFP) or hepatoma (AFP), they are important because germ cell tumors are effectively treated with combination chemotherapy. Undifferentiated tumors presenting as CUP can be germ cell tumor, the recognition of which would lead to a substantial clinical response or even to cure.[6] 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.[7]

Polymerase chain reaction: 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.[8] 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.[9]

Electron microscopy: 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.[10]

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.

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.[11-13]

References:

  1. Haskell CM, Cochran AJ, Barsky SH, et al.: Metastasis of unknown origin. Current Problems in Cancer 12(1): 1-58, 1988.
  2. Ruddon RW, Norton SE: Use of biological markers in the diagnosis of cancers of unknown primary tumor. Seminars in Oncology 20(3): 251-260, 1993.
  3. Mackay B, Ordonez NG: Pathological evaluation of neoplasms with unknown primary tumor site. Seminars in Oncology 20(3): 206-228, 1993.
  4. Battifora H: Recent progress in the immunohistochemistry of solid tumors. Seminars in Diagnostic Pathology 1(4): 251-271, 1984.
  5. 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): 283-287, 1983.
  6. Greco FA, Hainsworth JD: Cancer of unknown primary site. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2423-2443.
  7. 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. Journal of Clinical Oncology 13(1): 274-282, 1995.
  8. Feinmesser R, Miyazaki I, Cheung R, et al.: Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. New England Journal of Medicine 326(1): 17-21, 1992.
  9. Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. Journal of the National Cancer Institute 86(5): 349-355, 1994.
  10. Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site: a newly recognized clinicopathologic entity. Annals of Internal Medicine 109(5): 364-371, 1988.
  11. Hanna WM, Kahn HJ: The ultrastructure of metastatic adenocarcinoma in serous fluids: an aid in identification of the primary site of the neoplasm. ACTA Cytologica 29(3): 206-210, 1985.
  12. Herrera GA, Reimann BE: Electron microscopy in determining origin of metastatic adenocarcinomas. Southern Medical Journal 77(12): 1557-1566, 1984.
  13. Mackay B, Ordonez NG: The role of the pathologist in the evaluation of poorly differentiated tumors. Seminars in Oncology 9(4): 396-415, 1982.


STAGE INFORMATION

There are divergent opinions 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 which are potentially responsive to treatment (e.g. lymphoma, germ cell tumor, breast or ovarian tumor) may be undertaken.

The chest radiograph has become an almost routine procedure in general medical practice. Although chest radiography is routinely performed, in the setting of CUP, there is no distinguishing feature that 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. The value of abdominal CT scans may be because of the inordinately high representation of pancreatic cancer in the CUP process.[1] However, with the exception of ovarian cancer, CT scans rarely identify treatable primary cancers.[2,3]

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 there is a large negative cost/benefit ratio 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.[4-9]

Cervical lymph nodes: A histologic diagnosis of metastatic carcinoma in cervical nodes requires a meticulous examination of the upper aero-respiratory tract. Histologically, these tumors are either squamous cell carcinoma, adenocarcinoma, 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.[10-12]

Poorly differentiated carcinomas: Investigators at Vanderbilt and elsewhere have defined a subpopulation of potentially curable patients with 1 or more of the following characteristics: aged younger than 50 years; midline tumor distribution, multiple pulmonary nodules or lymph nodes, elevated serum levels of beta human chorionic gonadotropins (HCG) or alpha-fetoprotein (AFP); cells positive for beta HCG or AFP by immunohistochemical stain; the presence of neuroendocrine granules; clinical evidence for rapid tumor growth; and/or tumors that were very responsive to chemotherapy or radiation therapy. In retrospective review, many of these patients, including some complete responders to chemotherapy, did not have any recognizable histopathologic features of germ cell tumors.[13-15] 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.[16]

Metastatic melanoma to a single nodal site: Approximately 5% of patients with malignant melanoma will present without a documented primary site. In such instances, the pattern of nodal metastasis generally follows the anticipated pattern for females and males with inguinal and axillary adenopathy, respectively. 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 characteristics are identical to those seen in stage II melanoma with a documented primary site.[5,17-19]

Isolated axillary metastasis: Most patients who present with nodal metastasis above the diaphragm ultimately are documented to have the most common supradiaphragmatic primary malignancy, i.e., lung cancer. However, the presence of isolated axillary metastasis in females raises another possibility. A few studies involving a small number of patients have shown that approximately one-half 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 one-half 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 10% 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.[1,4,20]

Inguinal node metastasis: 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.[21]

In addition to the above situations, there are certain instances in which significant palliation can be achieved 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 in thyroid cancer presenting as CUP than lung metastases.

References:

  1. Copeland EM, McBride CM: Axillary metastases from unknown primary sites. Annals of Surgery 178(1): 25-27, 1973.
  2. Abbruzzese JL, Abbruzzese MC, Lenzi R, et al.: Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. Journal of Clinical Oncology 13(8): 2094-2103, 1995.
  3. Karsell PR, Sheedy PF, O'Connell MJ: Computed tomography in search of cancer of unknown origin. Journal of the American Medical Association 248(3): 340-343, 1982.
  4. Patel J, Nemoto T, Rosner D, et al.: Axillary lymph node metastasis from an occult breast cancer. Cancer 47(12): 2923-2927, 1981.
  5. Klauser JM, Gutman M, Inbar M, et al.: Unknown primary melanoma. Journal of Surgical Oncology 24(2): 129-131, 1983.
  6. Schapira DV, Jarrett AR: The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma. Archives of Internal Medicine 155(19): 2050-2054, 1995.
  7. Levine MN, Drummond MF, Labelle RJ: Cost-effectiveness in the diagnosis and treatment of carcinoma of unknown primary origin. Canadian Medical Association Journal 133(10): 977-987, 1985.
  8. Maisey MN, Ellam SV: Investigating the adenocarcinoma of unknown origin (ACUP): a cost benefit analysis. Revue D'Epidemiologie et de Sante Publique 32(1): 57-61, 1984.
  9. Hainsworth JD, Greco FA: Carcinoma of unknown primary site. In: Stein JH, Ed.: Internal Medicine. Boston, MA: Little and Brown, 2nd ed., 1987, pp 1135-1139.
  10. DeSanto LW, Neel HB: Squamous cell carcinoma: metastasis to the neck from unknown or undiscovered primary. Otolaryngologic Clinics of North America 18(3): 505-513, 1985.
  11. Muraki AS, Mancuso AA, Harnsberger HR: Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology 152(3): 749-753, 1984.
  12. Silverman C, Marks JE: Metastatic cancer of unknown origin: epidermoid and undifferentiated carcinomas. Seminars in Oncology 9(4): 435-441, 1982.
  13. Greco FA, Vaughn WK, Hainsworth JD: Advanced poorly differentiated carcinoma of unknown primary site: recognition of a treatable syndrome. Annals of Internal Medicine 104(4): 547-553, 1986.
  14. Hainsworth JD, Wright EP, Gray GF, et al.: Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy. Journal of Clinical Oncology 5(8): 1275-1280, 1987.
  15. Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site: a newly recognized clinicopathologic entity. Annals of Internal Medicine 109(5): 364-371, 1988.
  16. Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. Journal of the National Cancer Institute 86(5): 349-355, 1994.
  17. Panagopoulos E, Murray DR: Metastatic melanoma of unknown primary origin: a study of 30 cases. Journal of Surgical Oncology 23(1): 8-10, 1983.
  18. Reintgen DS, McCarty KS, Woodard B, et al.: Metastatic malignant melanoma with an unknown primary. Surgery, Gynecology and Obstetrics 156(3): 335-340, 1983.
  19. Giuliano AE, Cochran AJ, Morton DL: Melanoma from unknown primary site and amelanotic melanoma. Seminars in Oncology 9(4): 442-447, 1982.
  20. Merson M, Andreola S, Galimberti V, et al.: Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer 70(2): 504-508, 1992.
  21. Hainsworth JD, Greco FA: Carcinoma of unknown primary site. In: Stein JH, Ed.: Internal Medicine. Boston, MA: Little and Brown, 2nd ed., 1987, pp 1135-1139.


NEWLY DIAGNOSED CARCINOMA OF UNKNOWN PRIMARY

The overwhelming majority of patients presenting with carcinoma of unknown primary (CUP) have disseminated disease that is relatively chemoresistant. However, there are a few situations in which potentially curative treatment can be delivered.

Cervical lymph nodes

All patients should undergo a careful head, neck, and lung evaluation including coronal computed tomography (CT) and/or magnetic resonance imaging (MRI) of the head and neck and blinded 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.[1] If no primary site can be determined, the following approaches should be considered:

- radical radiation therapy with curative intent to the cervical lymph nodes and possible sites of origin
- preoperative radiation therapy followed by radical neck dissection
- radical neck dissection
- radical neck dissection followed by postoperative radiation therapy to possible sites of origin [2]

More detailed information is available in the PDQ summary for metastatic squamous neck cancer with occult primary cancer.

Poorly differentiated carcinomas

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.

A series of 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%.[3] Carboplatin-containing regimens were found to have equal activity.[4] A paclitaxel-based combination yielded a 47% response rate in 35 patients with various histologic types of carcinoma of unknown origin.[5]

Poorly differentiated neuroendocrine carcinomas

In a series of 29 patients, 19 were treated with intensive cisplatin-based combination chemotherapy and 6 additional patients received doxorubicin combinations. Six patients achieved complete response and 4 of these patients were alive 19 to 100 months after diagnosis.[6]

Peritoneal adenocarcinomatosis

Another subset of patients with favorable response to chemotherapy and improved prognosis is women with peritoneal carcinomatosis of an adenocarcinomatous serous histologic type. Response and survival rates in these patients approach those seen in ovarian cancer patients and therapy appropriate for ovarian cancer should be used.[7,8]

Isolated axillary nodal metastasis

Although lung cancer is the most likely diagnosis, a certain proportion of these patients, especially females, have breast cancer. 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: lymph node dissection with or without mastectomy or radiation therapy to the breast with curative intent [9] or the above treatment plus adjuvant chemotherapy with an accepted therapeutic adjuvant approach for breast cancer, especially if breast cancer is proven or if other lymph nodes show adenocarcinoma.[10]

Inguinal node metastases

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's disease or non-Hodgkin's lymphoma, with CUP being less frequent. Treatment options:

- local excision alone
- superficial groin dissection alone
- local excisional biopsy with or without radiation, inguinal node dissection, or chemotherapy

In a small proportion of patients local excision alone is sufficient therapy. Initial therapy with radiation may be used successfully in certain patients, depending on extent of disease and individual patient characteristics. Isolated metastases also present in the central nervous system, liver, and genitourinary tract. More information can be found in the PDQ summaries for these malignancies.[11,12]

Melanoma (melanotic or amelanotic) occurring in a single nodal site

Approximately 5% of patients present with no detectable primary site. For such patients who present with a single site of nodal metastasis, the following treatment will yield a survival consistent with that obtained in conventional stage II melanoma:

- radical lymph node dissection

Multiple involvement

For those patients who present with widespread metastatic disease and for whom special studies reveal a probable primary tumor for which standard systemic therapy is available, such therapy should be administered, i.e., hormonal therapy for prostate and breast cancer, I-131 for thyroid cancer, 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.

The majority of patients will not have a definable primary source. For such patients, a variety of combination chemotherapy approaches has been tried with little success. No treatment can be considered standard at present. Therefore, such patients should be considered for available clinical trials.

References:

  1. Righi PD, Sofferman RA: Screening unilateral tonsillectomy in the unknown primary. Laryngoscope 105(5): 548-550, 1995.
  2. Davidson BJ, Spiro RH, Patel S, et al.: Cervical metastases of occult origin: the impact of combined modality therapy. American Journal of Surgery 168(5): 395-399, 1994.
  3. 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. Journal of Clinical Oncology 10(6): 912-922, 1992.
  4. 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. Annals of Oncology 3(8): 631-634, 1992.
  5. Hainsworth JD, Erland JB, Kalman LA, et al.: Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. Journal of Clinical Oncology 15(6): 2385-2393, 1997.
  6. Garrow GC, Greco FA, Hainsworth JD: Poorly differentiated neuroendocrine carcinoma of unknown primary tumor site. Seminars in Oncology 20(3): 287-291, 1993.
  7. Strnad CM, Grosh WW, Baxter J, et al.: Peritoneal carcinomatosis of unknown primary site in women: a distinctive subset of adenocarcinoma. Annals of Internal Medicine 111(3): 213-217, 1989.
  8. Dalrymple JC, Bannatyne P, Russell P, et al.: Extraovarian peritoneal serous papillary carcinoma: a clinicopathologic study of 31 cases. Cancer 64(1): 110-115, 1989.
  9. Merson M, Andreola S, Galimberti V, et al.: Breast carcinoma presenting as axillary metastates without evidence of a primary tumor. Cancer 70(2): 504-508, 1992.
  10. 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): 1461-1467, 1990.
  11. Guarischi A, Keane TJ, Elhakim T: Metastatic inguinal nodes from an unknown primary neoplasm: a review of 56 cases. Cancer 59(3): 572-577, 1987.
  12. Zaren HA, Copeland EM: Inguinal node metastases. Cancer 41(3): 919-923, 1978.


RECURRENT CARCINOMA OF UNKNOWN PRIMARY

The prognosis for any treated cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage. Deciding on further treatment depends on many factors, including the specific cancer, prior treatment, and site of recurrence, as well as individual patient considerations. Treatments that are under clinical evaluation are appropriate and should be considered when possible.

Date Last Modified: 05/1999

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