Case presentation by Dr.Ofail Alhusseiny

CARCINOMA OF UNKNOWN PRIMARY

في التعليمي الحسين مستشفىالمثنى محافظة

MDT Case discussion

A 45 y old female pt. presented to us as referred from AlNajaf to be having: a multiple bone secondaries (vertebral bodies T9,L3,L4 , multiple pelvic and skull osteolytic lesions) and diagnosed as CUP adenocarcinoma subtype via a vertebral bone lesion biopsy , she is chiefly complaining of severe back pain and discomfort , she has no any chest or urinary or GIT symptoms the abdomen is soft no hepatomegaly or splenomegaly no any tenderness she has no any gynecological problems she is married G5P5A0 she has negative breast exam and smooth soft bilateral thyroid lobe consistency , her CXR is clear , CT- abdomen (with no contrast) also clear, liver is normal, both kidneys are normal other than a benign cyst in the right kidney. She has no family history of any cancer, not a smoker, no previous medical diseases or admissions. She received palliative dose RT to the affected vertebrae.

U/S left breast:

It is of normal size and texture there is 0.7x0.6 cm hypoechoic mass surrounded by compressed breast tissue no calcification the mass seen in the lower lateral quadrant the picture suggestive of ca breast further investigations needed No axillary LAP.

What is next??

First to think of is the major problem here (bone met. And low S.calcium in order to avoid future pathological fractures that is majorly due to zometa drug S/E that she already took.

So advice for calcium supplement 1000mg daily +vit.D3 400 IUAnd continue on zometa .

And since the previous protocol has no any benefit and goes with CA breast and CA Ovary Now we need to change in to a 5FU based regimen in respect for CEA levels which is reasonable and a preferred step.

Other DDX ??? :

MULTIPLE MYELOMA—B2-microglubulin and bence jones protein and bone marrow biopsy for plasmacyts percent infiltration.

LUNG CANCER ---TTF1 marker.

COLON CANCER--- Proper colonoscopy.

Gastric cancer-- OGD

CERVICAL CANCER --- Colposcopy.

CA pancreas --- CA 19-9.

Thyroid cancer ---- T3,T4,TSH, calcitonin

WHAT IS THE MOST USEFUL TEST TO BE DONE TO REACH SUCH AN UNKNOWN PRIMARY?

•18F-FDG enhanced PET scan

SUMMARY ABOUT CUP

5% of all cancer patients, the primary origin of the tumor cannot be identified. Cancer of unknown primary site (CUP) ranks among the 10 most common malignancies.

The biology of the disease is unknown, and it is not clear if CUP represents a distinct entity with specific genetic/phenotypic aberrations.

less than 30% of patients have a primary site identified ante-mortem. postmortem examination reveals a putative primary site in 60% to 80% of all patients.

Unfortunately, the majority of patients with CUP (approximately 85%) are not included in those favorable patient subsets.

CLINICAL INVESTIGATIONS

All –CUP- patients should have :

1- A careful history taken. 2- Undergo a complete physical examination including head and neck, pelvic, and rectal examination.

3-Routine laboratory evaluation (blood counts and chemistry profile), urine analysis, and fecal occult blood test, although routine laboratory evaluation seldom shows any characteristic abnormalities in this group of patients

Radiological Studies

Using CT scans of the abdomen and pelvis, a primary tumor can be detected in 30% to 35% of patients.

A CT scan of the thorax is also relevant in CUP patients, because lung cancer is one of the most common primary tumors identified in patients with CUP.

In addition, CT scans can also be helpful in determining the extent of metastatic disease. Contrast enhanced CT scan of thorax, abdomen, and pelvis therefore constitutes the standard evaluation recommended in patients with CUP.

Endoscopic examinations

Should be performed only in patients with specific symptoms or signs. For example, patients with abdominal symptoms or occult blood in the stool should undergo endoscopic examination of the gastrointestinal tract.

Applied serological markers

PSA = Ca Prostate.CA125= Ca Ovary.CA 153= Ca breast.CEA= GIT origin tumors and medullary thyroid carcinoma. TTF1= Lung cancer.AFP and beta-HCG = Germ cell tumors.CA 19-9= Ca pancreas.

Histology and Immunohistochemistry

Pathologic evaluation has been reported to be the most specific and cost-effective method to determine type and origin of CUP.

The overall dominant morphological pattern of CUP is:1- Adenocarcinoma (50–70%).2- Poorly differentiated carcinoma (15–20%). 3- Squamous cell carcinoma. 4- Undifferentiated malignant tumor.5- Neuroendocrine carcinoma (each 5%).

The major problem is to distinguish between different specific types of adenocarcinomas and undifferentiated carcinomas.

The primary site of metastatic adenocarcinoma is most frequently the breast, colon, lung, ovary, pancreas, prostate, and stomach, with a high representation of lung and pancreatic tumors.

Undifferentiated tumors include mostly: lymphomas, germ-cell and neuroendocrine tumors.

For patients without an identified treatable primary tumor the use of empirical chemotherapy using current drugs and schedules should be a matter of frank discussion between patient and physician and there is no standard protocol.

Evaluation of performance status is important and for those who will be eligible for chemotherapy a median survival of 7 to 12 months can be obtained, with 25% to 45% of the treated patients alive after one year from the time of diagnosis.

Survival rates at two years are around 5% to 20% compared with a median survival of 2 - 3 months in an untreated population with unknown primary tumors.

Thank You