Cancer or Not Cancer

I remember the day like it was yesterday. It was my second year of medical school, and I was in  my Pathology class. The professor began the class by saying "A 32 year old female presented with fatigue, fever, night sweats, loss of appetite, unexplained weight loss for several weeks. How will you proceed ?". Ms.usha said "I would like to start with the basic investigations like CBC, CRP, ESR, Thyroid function tests to rule out infections, inflammation, hyperthyroidism, and blood disorders like leukemia". The professor asked "Mr.dheeraj do you want to add anything to the list?".  Mr.dheeraj said "Sir I would also add liver function tests, HBsAg, Anti-HCV and HIV tests to rule out Hepatitis and HIV". The professor said "Good, The Thyroid function tests and liver function tests were normal and HIV, HBV,HCV tests came back to be negative , However the ESR was elevated and CBP showed anemia and thrombocytopenia". The professor  asked students "so how will we proceed next? ". Mr.abhinav said "we can do peripheral blood smear sir". The professor said "Good, The peripheral blood smear showed RBC - Anisocytosis , Polychromasia and Giant platelets. So What are your differential diagnosis and what other tests will you do?". I said " Sir, Anisocytosis and Polychromasia can be seen in iron-deficiency anemia, which is most common type of anemia. Giant platelets can be a reactive change to anemia. So I would order iron studies like serum iron, ferritin, Transferrin and TIBC ". Mr.Dheeraj said "Sir, Anisocytosis and Polychromasia can also be seen in Megaloblastic anemia. Giant platelets can be seen in Megaloblastic anemia, Particularly if anemia is severe. So I would order serum Vitamin B12 and B9 levels". Mr.Shiva said "Anisocytosis and Polychromasia can also be seen in Myelodysplastic syndrome and Giant platelets indicate a platelet disorder seen in MDS and also these findings can be seen in Immune thrombocytopenia(ITP) and Thrombotic thrombocytopenia(TTP). So I would order for coagulation studies like PT, PTT, Fibrinogen and also ADAMTS13 assessment by ELISA to confirm my diagnosis".

The professor said "Iron studies, Vitb12 and B9 levels are normal ;  PT and PTT are also normal but fibrinogen levels are decreased and ADAMTS13 levels were found to be deficient and diagnosis of TTP was made. So patient was treated with plasma exchange and immunosuppressive medications. But the patient was not improving. So what will you do next?". Mr.Venu said "Sir, there can be delayed response to treatment in TTP patients. So we should wait for few days to weeks, so that patient can show improvement". The professor said "Good venu, But the symptoms were not improving even after weeks of treatment(Refractory to treatment). So how should we proceed?". I said "Sir, we may need to evaluate for other possible causes of symptoms. So I would order Imaging tests like X-ray and CT scan of chest and abdomen for tumors, lymphadenopathy; MRI brain for ischemic injuries and Bone marrow biopsy". The professor said " CT scan abdomen showed abdominal tumor and rest of imaging was normal. Bone marrow biopsy was consistent with TTP findings. The abdominal tumor was resected and was sent for histopathological analysis which showed abnormal lymphoid tissue with Onion skin appearance. After tumor removal, Patient symptoms have improved and ADAMTS13 levels normalized. So, what is your diagnosis?". The entire class was silent.

The professor said so let me summarize "A 32 year old female presented with fatigue, fever, night sweats, loss of appetite, unexplained weight loss for several weeks. ESR was elevated and CBP showed anemia and thrombocytopenia. Peripheral blood smear showed RBC - Anisocytosis , Polychromasia and Giant platelets. Fibrinogen levels are decreased and ADAMTS13 levels were found to be deficient. CT scan abdomen showed abdominal tumor. The abdominal tumor was resected and was sent for histopathological analysis which showed abnormal lymphoid tissue with Onion skin appearance. After tumor removal, Patient symptoms have improved and ADAMTS13 levels normalized. So what is the definitive diagnosis?" The entire class was silent.

So the professor said "Ok let me give a clue, HHV-8 immunostaining of biopsy showed presence of HHV-8 and serum levels of HHV-8 were elevated and serum IL-6 was elevated. So now can anyone tell the diagnosis?". I shouted "Castleman's disease". The professor said "Very good. The diagnosis is Acquired Thrombotic thrombocytopenic purpura due to antibody mediated ADAMTS13 deficiency precipitated by localized Castleman disease. The patient was treated accordingly"

The professor concluded the class by saying "Castleman's disease(Angiofollicular lymph node hyperplasia) is a rare disorder that affects the lymphatic system, causing the lymph nodes to be enlarged and inflamed. It can be unicentric (or) Multicentric. It can mimic lymphoma, So biopsy is the key. HHV-8 is known to cause Castleman's disease and also Kaposi's sarcoma"