Carcinoma of unknown origin

Improvements in histopathologic modalities for diagnosis have lessen the frequency of cancers of unknown origin by 2-5%, compared to historical estimates of 5 to 10%.

Fourth most common cancer-related cause of death in patients of both sexes.

Reported to be the seventh or eighth most frequent category of malignant disease and the fourth most common cancer related cause of death in both sexes.

As with all cancers, smoking, alcohol consumption, diabetes, and family, history are implicated as risk factors.

96% of cancers of in known primary have at least one genetic alteration, with a mean of 4 per tumor.

Approximately half of CUP‘s present as adenocarcinoma of unknown primary site by mucin production, and histologic type without pinpointing the exact origin.

Older patients are more likely to have cancer of unknown origin, with a median age of 65-90 years.

Potentially clinically relevant genomic alterations are identified in 85 percent of tumors.

Alterations in the RTK/Ras signaling pathway has been found in 72% is adenocarcinomas of unknown primary but only 39% of non-adenocarcinoma of unknown primary.

Cancer of unknown origin is the seventh most common malignancy.

Typically patients present with incidental findings to clinical signs of symptoms of multiorgan metastasis.

The lesion arises when metastases each detectable size faster than the primary tumor.

Primary can be identified in only 30-82% of cases at autopsy.

About 80,000 cases annually in the US.

Most cases are limited to epithelial and undifferentiated cancers.

histologic findings: adenocarcinoma 59% of cases, poorly differentiated or undifferentiated carcinoma or neoplasm in 31%, and squamous carcinoma in 9%, varied metastatici patterns include multiple sites in 33% of cases, liver in 25%, and lymph nodes in 7%.

Median survival of approximately 8-12months: The overall survival of cancer of unknown primary patients has not improved in over 30 years.

Cancer of unknown primary has been classified into favorable and unfavorable subset with favorable cancer, referred to distinct clinical pathological manifestations in which the pattern of metastatic disease is typical of certain known cancers and comprises 20% of cancers of unknown primary and is associated with the better prognosis than unfavorable disease.

The larger unfavorable subset of CUP is associated with poor survival.

Survival in patients with CUP is worse than those in patients with metastatic cancers of known primary associated with male sex, poor performance status, adenocarcinoma, high number of metastases, the presence of liver, or peritoneal metastasis, high neutrophil:lymphocyte ratio, and molecular alterations such as KRAS or NRAS and CDKN2A deletion all implicated as adverse prognostic factors.

Patients with isolated nodal metastases have a better prognosis with appropriate therapy.

Metastatic adenocarcinoma represents the most common histology in patients with cancer of unknown primary, with lung or pancreatic as the most common source.

Approximately two thirds of patients with cancer of unknown origin are adenocarcinomas with mucin production, tubule formation, and immunohistochemistry findings of adenocarcinoma.

About one third of cancers of unknown origin are a mix of non-adenocarcinoma including squamous cell carcinoma, neuroendocrine carcinoma, small cell and large cell undifferentiated carcinomas.

With adenocarcinoma the median survival is about 3 months.

In women with disseminated peritoneal carcinomatosis the primary tumor usually originates in the ovary.

Adenocarcinoma to the axilla in men the lung, GI and GU tracts are the main considerations for primary lesion.

Adenocarcinoma to the axilla in a woman suggests breast cancer as the primary lesion.

Squamous cell cancer to cervical nodes head and neck cancers should be suspected as the primary lesion.

Squamous cell carcinoma to the neck has a 5-year survival rate of 30-50%.

Involving the head and neck-metastases to the cervical lymph nodes is seen in approximately 3-5% of cases of head and neck cancers.

Involving the head and neck-most cervical lymph nodes arise from upper aerodigestive tract sites, but may come from the thyroid, lung or esophagus.

Involving the head and neck-squamous cell carcinoma represents about 90% of metastatic lesions to the cervical lymph nodes with unknown primary tumors-melanoma, adenocarcinoma and lymphoma account for the remaining lesions.

Involving the head and neck-incidence in Denmark found to be 0.34 per 100,000 population (Grau).

Involving the head and neck-fewer than 60% of squamous cell cancers of the neck of unknown origin are identified as to the primary lesion.

Unknown primary cancers of the head and neck originate mostly from the palatine tonsil, base of the tongue or the nasopharynx.

Unknown primary cancers of the head and neck require an evaluation by a head and neck specialist, with examination of the head and neck skin, and endoscopy of the nasopharynx, or pharynx, larynx, and hypopharynx with palpation of the tonsil and base of tongue.

Presently, there is no consensus on the diagnostic tests required for all patients at the time of clinical presentation.

Unknown primary cancers of the head and neck-evaluation will reveal the primary in 52-55% of cases (Jones).

Metastatic squamous cell carcinoma of an unknown primary accounts for less than 5% of tumors within their head and neck region.

The primary may be too small to detect or it may disappear after metastasizing.

Aneuploidy identified in 70% of such lesions

No unique chromosomal or molecular abnormalities have been identified.

High degree of expression of VEGF in all cases.

Most widely accessible diagnostic scanning test is the PET scan.

Light microscopic examination of tissue with immuno phenotyping is the mainstay in the diagnosis of CUP.

Immunohistochemistry marker stains and gene expression/molecular profiling assays have led to improvements in the evaluation of such tumors and allows treatment with more specific agents with better survival.