A 58-year-old male presented to medicine outpatient department with complaints of abdominal distension, loss of appetite, and weight loss for the last 2-3 months. The patient had midline neck swelling for the last 15 years which approximately measured 4 cm x 4 cm and was firm, nodular, and nontender. There was no history of fever, cough with or without expectoration, hematemesis, melena, loss of consciousness, or altered sensorium. The patient was not a known case of diabetes mellitus, hypertension, or any other chronic systemic illness. He had no history of tuberculosis or any history of contact for the same. On general examination, the patient was conscious and well oriented. His blood pressure and pulse rate were within normal limits as per his age. However, pallor was noted. He did not have icterus, clubbing, cyanosis, pedal edema, peripheral palpable lymphadenopathy, and his jugular venous pressure was also not raised.
Per abdominal examination revealed moderate hepatosplenomegaly and ascites. Rest of the systems examined did not reveal any abnormality.
Thyroid function tests showed elevated levels of thyroid-stimulating hormone: 21.005 pg/ml (normal - 0.55-4.78 pg/ml) and decreased levels of free-T3: 1.3 pg/ml (normal: 2.3-4.2 pg/ml) and T4: 0.58 ng/dl (normal: 0.89-1.76 ng/dl). Other routine biochemical parameters were within normal limits.
Hemogram of the patient showed hemoglobin - 8.8 g/dl, total leukocyte count - 16,200/muL, and platelets - 2.6 lakhs/muL. Peripheral blood smear examination showed leukocytosis with the presence of immature cells of myeloid series (differential leukocyte count as: myelocytes - 17%, metamyelocytes - 10%, polymorphs - 46%, lymphocytes - 21%, monocytes - 02%, basophils - 02%, eosinophils - 02%). Five nucleated red blood cells were noted per 100 white blood cells. Red blood cells showed mild anisocytosis with the presence normocytic normochromic to microcytic hypochromic cells. Few tear drop cells and polychromasia were also noted. Overall findings were of leukoerythroblastic blood picture.
Bone marrow aspiration examination was done. However, bone marrow smears were markedly diluted with peripheral blood showing few maturing cells of myeloid and erythroid series. Bone marrow biopsy obtained was inadequate.
Ultrasound of neck and abdomen was done. Thyroid was diffusely enlarged with multiple heteroechoic nodules (largest measuring 39 mm x 36 mm) seen scattered diffusely in the thyroid with peripheral calcification, suggestive of multinodular goiter. Ultrasound of the abdomen revealed hepatosplenomegaly and gross ascites with omental caking and peritoneal thickening which was suggestive of tubercular etiology keeping in with the high incidence of tuberculosis in India [Figure 1a]. Hence, the patient was further investigated for tuberculosis with ancillary tests but showed negative results (ascitic fluid adenosine deaminase level - 10.0 [normal <40 U] and negative Montaux test). Chest X-ray showed evidence of bilateral pleural effusion with focal consolidation.
Further, contrast-enhanced computed tomography (CECT) abdomen and chest showed evidence of chronic liver disease with portal hypertension (portal vein pressure 20 mm Hg), hepatosplenomegaly, and few retroperitoneal lymph nodes. Gross ascites along with thickened peritoneum were also noted [Figure 1b]. CECT chest revealed bilateral moderate pleural effusion with underlying segmental lung collapse and consolidation. Moderate pericardial effusion was also found [Figure 1c].
Fine-needle aspiration cytology of thyroid swelling was revealed benign cytology with calcified material and debris in a background of thin colloid. Ascitic fluid was sent for the cytological examination. Grossly, 2 ml of thin blood mixed fluid was received. Multiple smears prepared after cytocentrifugation and were air dried and fixed in 95% ethyl alcohol and subsequently stained with Giemsa and Papanicolaou stain, respectively. Smears were highly cellular and revealed all the three lineages of hematopoietic cells with a predominance of myeloid series cells which were seen in all stages of maturation along with occasional cells of erythroid series and many megakaryocytes [Figure 2a]. The morphology of megakaryocytes was clearer in Papanicolaou-stained smears revealing multiple distinct nuclei [Figure 2b]. Furthermore seen were many mature lymphocytes, few reactive forms, plasma cells, and histiocytes in a thin hemorrhagic background. Few of the histiocytes showed evidence of emperipolesis. Cell block was prepared from the peritoneal fluid which also showed evidence of EMH [Figure 2c]. Based on the cytomorphological findings, a diagnosis of EMH in peritoneal fluid was given. Cytological examination of pleural fluid was also consistent with EMH.
Cytological diagnosis urgently prompted a relook in the radiological and the hematological workup and a repeat bone marrow aspiration and biopsy was done. Smears were again markedly diluted with blood with sparse myeloid and erythroid cells. However, megakaryocytes were easily noted. However, bone marrow biopsy showed markedly hypocellular marrow with diffuse fibrosis of marrow spaces and focal vascular proliferation [Figure 2d]. Few megakaryocytes were seen [Figure 2d; inset]. Reticulin stain showed diffuse and dense increase in reticulin with extensive intersection [Figure 2e]. Coarse bundles of collagen were seen diffusely staining blue on Masson's trichrome stain [Figure 2f]. A diagnosis of primary myelofibrosis (PMF) was given.
A radiologic relook also was consistent with the possibility of EMH mimicking tuberculosis. Liver biopsy was done to evaluate the patient, based on the CECT findings for any association with cirrhosis. Histology showed evidence of EMH and no evidence of cirrhosis was noted. Simultaneously, molecular testing for BCR-ABL rearrangement (polymerase chain reaction quantitative) and for JAK2 V617F mutation showed negative results. Finally, a diagnosis of PMF with EMH was made.
The patient was mainly given supportive treatment, the drug Carvedilol (3.125 mg twice a day) for the portal hypertension and the patient was referred to a higher oncology center for further management.