Cancer of unknown primary origin overview

# Overview
Cancer of unknown primary origin or CUP is the diagnosis of metastatic cancer when the anatomic site of origin remains unidentified. Cancer of unknown primary origin is common, and it accounts for 25% of all cancers. Cancer of unknown primary origin may be classified according to pathology findings into 4 groups: adenocarcinomas, poorly differentiated carcinomas, squamous cell carcinomas, and carcinomas with neuroendocrine differentiation. The majority of patients with cancer of unknown primary origin may be initially asymptomatic. Early clinical features include fatigue, weight-loss, and loss of appetite. If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death. The treatment for cancer of unknown primary origin will depend on several factors, such as: metastatic origin, biopsy findings, patients age, and performance status. The 5-year survival of patients with cancer of unknown primary origin is less than 2%.

# Historical Perspective
Cancer of unknown primary origin was first discovered in the 1980s and was based solely on imaging studies.

# Classification
Cancer of unknown primary origin may be classified based on light microscopy of the tissue biopsy into 4 groups including adenocarcinomas, squamous cell carcinomas, poorly differentiated tumors, and carcinomas with neuroendocrine differentiation.

# Pathophysiology
The exact pathogenesis of cancer of unknown primary origin is not fully understood. Several studies noted consistency between metastatic cancer of unknown primary and metastases with known primary origins based on chromosomal abnormalities and over expression of several genes.

# Causes
Several studies have evaluated the chromosomal and molecular anomalies found in cancers of unknown primary; however, they could not identify unique causes of metastasis of unknown primaries relative to those with known primary origins.

# Differential Diagnosis
Cancer of unknown primary is a diagnosis of exclusion; hence, all other differentials in addition to primary tumor location must be ruled out prior to diagnosis.

# Epidemiology and Demographics
The prevalence of cancer of unknown primary origin is approximately 10 cases per 100,000 individuals worldwide. Patients of all age groups may develop cancer of unknown primary origin. In most cases cancer of unknown primary origin affects men and women equally. There is no racial predilection to cancer of unknown primary origin.

# Risk Factors
There are no established risk factors specific for cancer of unknown primary origin.

# Screening
There is insufficient evidence to recommend routine screening for cancer of unknown primary origin.

# Natural History, Complications, and Prognosis
Early clinical features include fatigue, weight-loss, and loss of appetite. Common complications of cancer of unknown primary origin, may include: hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome, hematologic disorders, and malignant effusions. Prognosis is generally poor, and the average survival time of patients with cancer of unknown primary origin is approximately 6-12 months after diagnosis.

# Diagnostic Studies

## Diagnostic Study of Choice
The diagnosis of cancer of unknown primary origin is made when the following diagnostic criteria are met: tissue biopsy indicating malignancy and all known primary origins of cancer are ruled out. The initial approach may vary on a case-by-case basis; however, the diagnosis is made after histopathological and clinical testing.

## History and Symptoms
The majority of patients with cancer of unknown primary origin are asymptomatic.

## Physical Examination
There are no remarkable findings in the physical examination of CUP patients; the presentation is variable and depends on many factors including the primary tumor's origin and extent of organs involved.

## Laboratory Findings
There are no specific diagnostic laboratory findings associated with cancer on unknown primary origin; however, certain abnormal laboratory findings may help in locating the primary origin of the tumor.

## X-Ray
A chest x-ray is a prerequisite in the diagnosis of cancer of unknown primary; however, its value is of less significance when it comes to locating the primary tumor or differentiating it from a metastatic lesion.

## Ultrasound
There are no specific echocardiography or ultrasound findings associated with cancer of unknown primary origin. However, a testicular or breast ultrasound may be helpful in the localization of the primary origin of the tumor in certain cases.

## CT Scan
CT scan may be helpful in the diagnosis of cancer of unknown primary origin.

## MRI
There are no MRI findings associated with cancer of unknown primary origin.

## Other Imaging Findings
There are no other imaging findings associated with cancer of unknown primary origin.

## Other Diagnostic Studies
Other diagnostic studies for cancer of unknown primary that may help establish the origin of the tumor include tumor markers, diagnostic tonsillectomy, and gastrointestinal endoscopy.

# Medical Therapy
The treatment for cancer of unknown primary origin will depend on several factors, such as metastatic origin, biopsy findings, patients age, and performance status. Medical therapy for cancer of unknown primary origin should be adjusted on an individual basis and according to well-defined clinical and pathological subsets.

# Surgery
Surgical intervention is not recommended for the management of cancer of unknown primary origin.

# Primary Prevention
There are no primary preventive measures available for cancer of unknown primary origin.

# Secondary Prevention