Cancer of unknown primary (CUP) accounts for approximately 3 percent of all neoplasms and is a heterogeneous group of neoplasms with a varied clinical course and prognosis. They can occur at any age, but most often in the sixth decade of life. They are found with the same frequency in women and men.

Neoplasms of unknown primary location(CUP, Cancer of unknown primary) are diagnosed by cytological or histopathological examination of metastatic lesions, while the location of the primary tumor cannot be determined on the basis of routine diagnostic tests. The presence of metastases is most often found in the liver, bones, lungs, lymph nodes, pleura and brain. Due to the fact that these tumors are diagnosed in the spreading stage, their treatment is usually palliative.

Tumors of unknown primary site: clinical symptoms and prognosis

In neoplasms of unknown primary location, the symptoms are usually associated with the location of metastatic lesions. Some patients may experience general symptoms of advanced cancer, such as anorexia, weight loss, and a feeling of weakness or fatigue. The examination often shows enlarged peripheral lymph nodes, signs of pleural effusion, bone soreness and enlarged liver.

The prognosis of patients varies greatly and depends on many clinical factors.

For example, in patients with head and neck neoplasms, survival for several years depends on the local stage of the tumor and its location, but after aggressive combined treatment it ranges from 30% to 70%. The occurrence of squamous cell carcinoma metastases is associated with a poor prognosis - five-year survival is around 5%, and the average survival is just over 6 months.

The presence of axillary lymph node metastases is associated with a different 5-year survival depending on gender - in women it is about 65% and in men it is about 25%.

Detection of peritoneal metastases in ovarian cancer is associated with a low 3-year survival rate of 10-25%.

In the case of single metastatic lesions without a localized focusthe primary 5-year survival rate is about 60%, while in patients with a revealed focus it decreases to 30%.

Positive prognostic factors include good general condition, female gender, localization of metastatic lesions only in the lymph nodes or in soft tissues, weaving of highly differentiated and squamous cell carcinoma, and normal serum concentration of LDH and albumin.

Adverse prognostic factors include poor general fitness, numerous metastases in the parenchymal organs, glandular carcinoma, elevated levels of serum alkaline phosphatase and lactate dehydrogenase, hypoalbuminemia and the location of metastatic lesions in supraclavicular lymph nodes.

Tumors of unknown primary location: diagnostics

In the diagnosis of neoplasms of unknown primary location, blood counts and biochemistry are used, as well as imaging and endoscopic examinations, as well as pathomorphological and molecular examinations.

In each case of neoplasm of unknown primary location, it is advisable to perform a blood count as well as the assessment of kidney and liver function. The determination of tumor markers is also used. For example, the determination of alpha-fetoprotein (AFP) is performed in the presence of liver metastases, the determination of CA15-3 is important in the case of metastatic adenocarcinoma to the axillary lymph nodes, and the determination of CA125 is important in women with neoplastic involvement of the peritoneum. In men with bone metastases, specific prostatic antigen is determined, and in the presence of a neoplastic lesion in the mediastinum or in the retroperitoneal region, determination of the concentration of chorionic gonadotropin (β-HCG) and AFP may be considered due to the possibility of an ectopic germ cell tumor.

In the case of imaging examinations, computed tomography of the chest, abdominal cavity and pelvis is most often performed. When lymph nodes are involved in the neck, computed tomography of the neck and face is required.

In addition, magnetic resonance imaging, positron emission tomography (PET) and ultrasound are also used.

The most common endoscopic examination is colonoscopy. It is performed in the presence of liver metastases and tumor involvement of the peritoneum, especially when the above-mentioned changes are accompanied by the presence of occult blood in the stool.

Pathomorphological examination of metastatic lesions is aimed at looking for the primary tumor site. However, it should be remembered that microscopic examination is rarely pathognomonic - the exception is the characteristic picture of clear cell carcinoma of the kidney, as well as the presence of signet cells,which are typical of stomach cancer.

Very often pathomorphological diagnostics is extended to include histochemical or immunohistochemical tests. Then, the determination of cytokeratin CK7 and CK20 is performed most often, and in the next stage - depending on the expression of cytokeratin and the clinical picture, specific antibodies are additionally detected. Such extended diagnostics makes it possible to determine with high probability the organ localization of a dozen or so neoplasms of unknown primary location.

Most often, metastatic lesions have an adenocarcinoma (75%). In this group of neoplasms, the primary site is usually located in the pancreas, lung, stomach, large intestine, and kidneys.

Squamous cell carcinomas account for about 10-15% of tumors of unknown primary location. In this case, the primary lesion is most often located in the head and neck region, in the lung and in the cervix.

Neuroendocrine neoplasms constitute a few percent of neoplasms with unknown primary location. The primary site is usually located in the digestive tract and upper respiratory tract.

It should be remembered that metastases of germinal tumors are the least frequent.

Clinico-pathological syndromes in neoplasms of unknown primary location

Metastasis of adenocarcinoma in axillary lymph nodes indicates the presence of a primary tumor in the breast. It should be remembered that in this situation mammography confirms the presence of a primary tumor in the mammary gland only in 10-20% of cases. Magnetic resonance imaging is a much better examination, which allows detecting the primary lesion in approximately 70% of patients.

A typical picture of advanced ovarian cancer is the infiltration of the peritoneum by adenocarcinoma accompanied by ascites. Clinical diagnosis is made on the basis of an elevated concentration of the CA125 marker.

The presence of bone metastases of adenocarcinoma in men is characteristic of lung cancer and prostate cancer. Less commonly, such changes originate in the kidney, thyroid or large intestine. Blastic metastases are characteristic of prostate cancer. Treatment is based on hormone therapy in prostate cancer and palliative chemotherapy in other cases. Painful metastatic lesions require palliative radiotherapy.

It should be remembered that in some patients with a single metastatic site, despite detailed clinical examinations and imaging studies, it is not possible to detect the location of the primary tumor. Surgical treatment and / or radiotherapy are used in these patients. It is worth remembering that usuallypatients from this group have a better prognosis.

Tumors of unknown primary location: treatment

The application of causal treatment, typical for a given tumor, is possible only in half of patients with tumors of unknown primary location. In other cases, the choice of treatment method depends on the histopathological structure of the tumor, the number and location of metastases, and the patient's overall performance status.

Surgical treatment is used in the presence of single metastatic lesions in easily accessible anatomical areas.

Another method of treatment is radiotherapy, which is usually palliative in nature. It is used in the case of metastatic lesions in the cervical, axillary and inguinal lymph nodes. It is also used in the case of painful metastatic changes in bones and compression syndromes.

Hormone therapy is most often used in patients with metastatic breast cancer and in patients with metastatic prostate cancer.

The last treatment option is chemotherapy, which may be considered in patients in good general condition. The treatment regimen depends on the structure of the tumor and its organ-related origin. For example, empiric chemotherapy commonly uses two-drug regimens that combine cisplatin with gemcitabine, irinotecan, or taxoids, or a combination of these drugs.

Category:

Oncology