Cancer of unknown primary headquarters is diagnosed when detected one or more metastatic offices and routine assessment (history, physical examination, chest radiography, biochemical tests of blood and urine complete histology) cannot locate the primary tumor.
The incidence of cancer with unknown primary headquarters is between 2-6%, being the 7th cause of cancer after lung, prostate, breast, cervical, colon and stomach.
The pathologist should be informed that the registered primary tumor is not indicated for planning additional special studies.
After the initial biopsy, light microscopy histological diagnosis establishes four major histological types.
1. Poorly differentiated malignant neoplasms (NMSD) 5% of all cancers with unspecified office. To elucidate the histological diagnosis required special techniques such as immunoperoxidase staining for electron microscopy and genetic analysis.
2. Adenocarcinoma of unknown primary location represents 60% of cancers of unknown primary headquarters.
3. Squamous cell carcinoma of unknown primary location is 5%.
4. Poorly differentiated carcinoma or adenocarcinoma is 30% of cancers with unspecified location.
Signs and symptoms: pain 60% hepatic tumor or other abdominal events 40%; 20% lymph nodes, bone pain or pathological fracture 15%, 15% respiratory manifestations, events NAS 5%, 5% weight loss, skin nodule 2%.
Headquarters metastatic most common were:
1. Lymph nodes
a) Superior cervical ganglia and medium enterprises. Most commonly primary Localization: head and neck tumors (nasopharynx, hypopharynx, base of the tongue, tonsils)
b) Lower cervical nodes usually have primary headquarters lung cancer
c) Supraclavicular lymph. Localization primary lung cancer or gastrointestinal tract
d) Lymph nodes. Localization primary breast, lung, melanoma, lymphoma
e) Inguinal lymph. Primary locations are cutaneous, genital, rectum, anus
2. Bone metastases in bone marrow
a) Bone metastases are the most common primary headquarters lung and pancreas.
b) Bone marrow metastases have primary headquarters lung, breast or prostate
3. Solitary pulmonary metastases. Localization – the most common primary colorectal tumors and sarcomas
4. Liver metastases. Prostate cancer or ovary may be the primary seat of liver metastasis unspecified starting point.
5. Brain metastases. Localization usually primary lung cancer
6. Cutaneous metastases. Primary Localization most commonly: lung, breast, kidney
Diagnostic assessment include: complete history, physical examination, biochemical tests of liver and kidney, blood count, chest X-ray, CT abdominal.
In patients with upper cervical lymphadenopathy and medium endoscopic examination is recommended nasopharynx, hypopharynx, larynx and esophagus biopsy of any suspicious areas Superior.
In patients with lower cervical and supraclavicular lymph nodes bronchoscopy is recommended.
Tumor markers. Determination of serum AFP BHCG and can suggest the diagnosis of germ cell tumors. ACE, CA -125, CA 19-9; CA 15-3 do not establish diagnosis but are useful in monitoring treatment when raised.
Rating pathological include: histopathology optical microscope, immunoperoxidase stain, its electronic microscope examination and genetic study.
By imunoperoxidase staining technique there are emphasized:
a) in carcinomas stained positive for EMA (epithelial membrane antigen)
b) in lymphoma test positive for leukocyte common antigen (CLA +)
c) in sarcomas test positive for desmin, vimentin and factor VIII antigen
d) in melanoma test positive for S-100 protein and 45 HMB-
e) in neuroendocrine tumors are positive for neuron specific enolase test (NSE), chromogranin and synaptophisine) prostate cancer test is positive for prostate specific antigen (PSA)
g) in germ cell tumors are positive tests for BHCG and AFP.
h) in breast cancer tests positive for estrogen receptors and progesterone.
Electron microscopy can diagnose a sarcoma poorly differentiated neuroendocrine tumors (neurosecretory grains), melanoma (melanosomes and premelanosomes) can differentiate lymphoma carcinoma
Genetic analysis of chromosomal abnormalities diagnostic use is limited.
Detection of chromosomal translocation t (14:18), t (8:14) or t (11:14) is useful in the diagnosis of lymphoma.
Abnormalities of chromosome 12 present in the germ cell tumors.
Detection of Epstein-Barr virus genome is associated with nasopharyngeal carcinoma.
I. poorly differentiated malignant neoplasms of unknown primary office (NMSD) – 5%.
After further testing (immunoperoxidase staining electron microscopy, genetic analysis), NMSD are:
a) 35-65% Non-Hodgkin malignant lymphoma
b) 15% melanoma and sarcoma
c) 20-50% carcinoma
II. Adenocarcinomas of unknown primary office (ASPN) is 60%. This group included well-differentiated and moderately differentiated adenocarcinoma. Headquarters are most common metastatic lymph nodes, lungs, bones and liver.
The primary premises cancer were identified at autopsy as being the lung and pancreas (40%), stomach, colon and liver. Most patients in this group have disseminated metastases and a bad performance status.
They have identified four subsets of patients with adenocarcinoma:
1. Unknown primary peritoneal locations in women
It is most commonly caused by ovarian cancer. Less may occur from a carcinoma of the gastrointestinal tract, lung or breast. A primary peritoneal described the primary seat is not in the ovaries or other establishment.
2. Adenocarcinoma metastases in the lymph nodes in women
The most common are caused by breast cancer. After biopsy lymph nodes and determine the level of tumor estrogen receptor and progesterone if not identified other metastases, patients with axillary lymph node metastasis of breast cancer are classified as stg.II.
3. Adenocarcinoma metastases in men
It must be measured in serum PSA level and immunoperoxidase staining performed on biopsy for PSA piece. Their presence of prostate adenocarcinoma suggests.
4. Adenocarcinoma metastases classified in the first three categories represent 90% of cases.
III. Squamous cell carcinoma of unknown primary office is 5%
1. Cervical squamous cell carcinoma metastases and supraclavicular lymph:
a) the superior cervical ganglia metastases and medium
The tumors are mainly head, neck and upper esophagus
b) Lower cervical metastases and supraclavicular lymph. They are mainly determined by lung cancer.
2. Squamous cell carcinoma metastases in inguinal nodes. The seat of mayor in these cases may be in the genital or anal: vulva, vagina, cervix, penis, scrotum and anus.
3. Squamous cell carcinoma metastases of other sites. The seat is mainly primary lung cancer. More rarely the primary seat is given to the head and neck tumors, esophagus, anus, skin.
IV. Poorly differentiated carcinoma or adenocarcinoma of unknown primary headquarters is 30%
1. Specific carcinoma 1%
2. Lymphoma, melanoma, sarcoma 3%
3. Poorly differentiated carcinoma or poorly differentiated adenocarcinoma 26%
This group of poorly differentiated carcinoma (poorly differentiated adenocarcinomas) includes the following entities:
a. germ cell tumors
b. Neuroendocrine tumors:
Small cell -tumors “oat”. The seat can be rare lung or extrapulmonary. They include small cell carcinoma, atypical carcinoid and neuroendocrine carcinoma poorly differentiated.
Poorly differentiated neuroendocrine -carcinomas 10% of poorly differentiated carcinomas. They are diagnosed as positive for chromogranin imunoperoxidase study, NSE and synaptophisine. They are called primitive neuroectodermal tumors.
I. Adenocarcinomas (60%). Treatable clinical subsets:
1. Primary peritoneal carcinoma in women
This syndrome has been called serous carcinoma or carcinoma extraovarian multifocal primary peritoneal. Headquarters is neither primary ovarian or in another abdominal organ. Treat as std.III ovarian cancer patients. Laparotomy and cytoreductive is recommended surgery followed by chemotherapy treatment with:
Cisplatin 75 mg / m2 i.v. day 1
Taxol 175 mg / m2 i.v. Day 1.
Repeat 3 weeks
Complete responses occurred in 20% and survival at 2 years disease free is de16%.
2. Isolated axillary node metastasis in women
70% of axillary lymph node metastases of adenocarcinoma are determined by breast cancer. Unless otherwise, metastases patients are treated as stage II breast cancer.
Therapeutic options include:
a) Modified radical mastectomy with axillary lymphadenectomy or
b) Breast radiotherapy after axillary lymph node dissection. After radiotherapy or surgical treatment is recommended adjuvant chemotherapy.
In patients with estrogen receptor positive and progesterone hormone therapy is recommended.
3. Men with bone metastases
In patients with osteoblastic bone metastases or increased serum PSA or PSA positive staining for immunoperoxidase similar hormonal therapy is recommended metastatic prostate cancer therapy
4. Patients with a single metastatic office
Aggressive local therapy is recommended consisting of resection and / or radiotherapy. After topical treatment chemotherapy is recommended.
5. Metastatic adenocarcinoma that does not fall within the previous subsets.
90% of patients with metastatic adenocarcinoma fall into this subgroup. These patients are treated with chemotherapy. Favorable response to chemotherapy is obtained in tumors located in the lymph nodes, poorly differentiated histology and women. Patients with liver metastases and bone respond poorly to treatment.
see table no. 55 Scheme of chemotherapy
Docetaxel 75 mg / m2 / day i.v. Day 1
Cisplatin 75 mg / m2 / day i.v. on day 1
Repeat 3 weeks 4-6 cures
Docetaxel 65 mg / m2 / day i.v. on day 1
Carboplatin AUC 5
Repeat 3 weeks 4-6 cures
Taxol 200 mg / m2 i.v. 1 hour infusion Day of January
Carboplatin AUC 6 iv Day 1
Etoposide 1-10 days po 50 mg / day alternating with 100mg / day
Repeat 21 days 4-6 cures. 40-50% response rate
Median survival is 10 months. 1-year survival is 40%, 20% at 2 years, 3 years of 14-17%.
II. Squamous cell carcinoma of unknown primary location 5%
1 in cervical ganglia metastases and supraclavicular
a) superior cervical ganglia metastases and medium enterprises.
The seat is always primary tumor in the oropharynx, hypopharynx, nasopharynx, larynx and esophagus higher.
Local treatment is modified radical lymph node dissection be either external beam radiation. Radiation must include irradiation field nasopharynx, oropharynx, hypopharynx and. Relapses occur less often after radiotherapy.
After topical treatment is recommended adjuvant chemotherapy plus Taxol Carboplatin or PF type. Survival at five years is 30-40%.
b) lower cervical metastases and supraclavicular lymph. The seat is usually primary lung cancer. The recommended treatment consists of radiotherapy and chemotherapy local.
2. squamous carcinoma in inguinal lymph nodes. The primary location is genital and anorectal. If the primary seat is not found, treatment consists of surgical resection with or without radiotherapy. Adjuvant chemotherapy is recommended.
3. squamous carcinoma with other offices. The seat is most often primary lung. It is recommended that C. T. lung and bronchoscopy. In patients with good dependable performance status chemotherapy regimens recommended that non-small cell lung carcinoma.
III. Poorly differentiated carcinoma 30%
3% are represented by lymphomas, sarcomas, melanomas and are treated according to the diagnosis.
a) Amelanocitar melanoma: Diagnosis is determined by staining positive imunoperoxidase protein and HMB-45 S 100, and the electron microscope highlights premelanosomes or melanosomes. Patients diagnosed so respond well to treatment based on cisplatin and there are chances of long term survival.
b) extragonadal germ cell cancer syndrome
It is suspected in young patients with retroperitoneal tumor masses, mediastinal or multiple pulmonary nodules with high levels of BHCG and AFP, poorly differentiated carcinoma histology and genetic analysis of chromosome 12p abnormalities. Full syndrome should include the following criteria:
1) Young men <50 years
2) localized retroperitoneal or mediastinal tumors or multiple pulmonary nodules
3) rapid tumor growth with symptom-diagnosis interval <3 months
4) High levels of BHCG or AFP or both
5) Good response to prior treatment radiotherapy or chemotherapy.
Treatment consists of 4 courses BEP:
Cisplatin 120 mgm2zi, IV zilele1-5,
Etoposide 100mgm2, IVzilele 1-5
Bleomycin UIm2IV 30, days 1,
Repeat 21 days.
c) Small cell carcinoma. The primary location can be lung or rarely extrapulmonary.
If the primary location is not identified we recommend chemotherapy for small cell lung cancer. The treatment regimen is Cisplatin plus Etoposide.
d) poorly differentiated neuroendocrine carcinoma. These tumors are called primitive neuroectodermal tumors. The diagnosis is based on electron microscopy and staining that highlights peroxidases neurosecretory granules positive for NSE and synaptophisine chronogranin. These tumors are very sensitive to chemotherapy. Patients with a single seat tumor can be cured only with local treatment followed by chemotherapy.
1. Cisplatin 20 mg / m2 / day i.v. days 1-5
Etoposide 100 mg / m2 / day i.v. days 1-5
Repeat 3 weeks with complete response rate of 28% overall response rate of 71%.
2. Taxol 200 mg / m2 i.v. Day 1
Carboplatin AUC 6 iv Day 1
Etoposide 50 mg / day alternating with 100mg / day days 1-10
21 is repeated at days 4-6 cycles
e) patients with poorly differentiated carcinoma classified in the categories above
For patients with good performance status plus Cisplatin chemotherapy is recommended Etoposide plus Taxol or Carboplatin and Etoposide.
The overall rate of response was 64% with complete responses in 20%. Median survival was 20 months and survival at 8 years of 13%.
For patients with bad performance status 5 FUR monotherapy is recommended 500 mg / m2 x 5 days or symptomatic treatment.