Synchronous Thyroid Involvement in Plasma Cell Leukemia Masquerading as Hashimoto's Thyroiditis: Role of Ancillary Cytology Techniques in Diagnostic Workup.

Neoplastic plasma cell involvement of thyroid is an uncommon condition, and it may involve thyroid in multiple myeloma or solitary plasmacytoma. Its clinical and pathological features are not well understood. We present a rare case of synchronous thyroid involvement in plasma cell leukemia presenting as thyroid nodule with primary hypothyroidism. Simultaneous cytology, immunocytochemistry, FISH analysis with 13q14.3 and TP53 on cytology smears and haematology workup were performed to diagnose and to understand disease pathobiology with poor outcome.

Plasma cell leukemia: A case series from South India with emphasis on rarer variants.

Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasia. They occur de novo (primary) or as a late manifestation of multiple myeloma (secondary). Patients present with anemia, thrombocytopenia, renal failure, organomegaly and extramedullary manifestations. We are presenting this series as it is the second largest series from India (16) with 4 young cases (under 40 years of age), more number of female patients and two having 'hairy cell' morphology. It is recommended that techniques like immunophenotyping and protein electrophoresis be performed, whenever the morphology is not characteristic of plasma cells.

Hairy cell leukemia: clinicopathological and immunophenotypic study.

Hairy cell leukemia (HCL) is a rare neoplasm of mature small B lymphoid cells with characteristic circumferential 'hairy projections' involving the peripheral blood, bone marrow and splenic red pulp. With the advent of immunophenotyping and newer treatment modalities, prolonged remission can be achieved after a definitive diagnosis. Due to the rarity of this condition and presence of only a few case series from India, this work was undertaken. The aim was to study the clinico-pathologic and immunophenotypic features of all cases diagnosed as hairy cell leukemia. The cases were retrieved from Hematopathology records, between 1991 and 2012. The complete clinical details, investigations, treatment and follow-up were obtained from Medical Oncology records. The peripheral blood picture, bone marrow cytology and trephine sections along with special stains were reviewed. There were 12 cases of HCL during the study period with a M:F ratio of 11:1. Of these, ten were diagnosed as classical HCL and two as variant HCL. The most common clinical manifestations were fever, easy fatigability and weakness. Splenomegaly was present in 81.8 % cases. Though all the patients showed some form of cytopenia, there were three (25 %) patients with leucocytosis. The smears from all patients showed atypical lymphoid cells with circumferential hairy projections. TRAP was positive in 9 patients (81.8 %). Immunophenotyping was done in six cases, four were confirmed as HCL and two were diagnosed as HCL-v. The patients treated with Cladribine generally had a good response. The characteristic morphology of the hairy cells; along with correlation with the clinical features, TRAP positivity and immunophenotyping by flow cytometry is essential for diagnosis. Treatment response with Cladribine is good and has prolonged remission rates.

Morphologic Changes in the Bone Marrow in Patients of Chronic Myeloid Leukemia (CML) Treated with ImatinibMesylate.

Imatinib mesylate (Gleevec) is an effective treatment for chronic myeloid leukemia (CML). Though cytogenetic and molecular analyses are essential disease monitoring parameters in CML bone marrow morphological response is not well defined. We examined marrow samples from 40 patients with CML which have at least 2 or more follow-up marrow. A significant positive correlation with complete cytogenetic response shown for normalization of cellularity (P = 0.0097), absence of dry tap (P = 0.0368) and abnormal megakaryocytes (P = 0.005), reduction of blasts (P = 0.019), basophils (P = 0.031), M:E index (P = 0.018) and fibrosis (P = 0.018). Morphological criteria for complete cytogenetic response in CML patients treated with Imatinib can be defined.Morphologic response is also of potential clinical value in addition to cytogenetic and molecular response in patients of CML treated with Imatinib.

Evaluation of Cytopenias Occurring in Imatinib Treated Chronic Myeloid Leukemia (CML) Patients.

Imatinib Mesylate, a Tyrosine Kinase inhibitor, is presently the drug of choice for Chronic myeloid leukemia (CML). During therapy, a few patients develop myelosuppression and present with cytopenias. To study the bone marrow morphology in imatinib treated CML patients presenting with persistent cytopenias. The cases were retrieved from the Hematopathology record files, Department of Pathology; the study period being January 2008-June 2009. Cases of CML on Imatinib presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenias with bone marrow studies, were included in the study. The morphology of all cases was reviewed with cytogenetic studies. Follow-up details were obtained from the Medical Oncology records. During the study period, 683 Imatinib treated CML patients had bone marrow studies as part of their follow-up investigations. Of these, 60 patients (9%) had some form of persistent cytopenia. The patients ranged from 21 to 75 years of age with a median age of 38 years. The male:female ratio was 1:1. There were 46 patients with ≥grade 2 anemia, 25 patients with ≥grade 2 neutropenia and 37 patients with ≥grade 2 thrombocytopenia. Of these, 18 patients had bicytopenia and 13 cases had pancytopenia. The marrow evaluation revealed morphologic response in 30 patients, persistent marrow disease in five patients, marrow hypoplasia in six patients, extensive stromal changes including fibrosis in five patients, megaloblastic erythropoiesis in 11 patients and disease progression to accelerated or blast crisis in three patients. Various degrees of cytopenias may occur in few patients of CML on imatinib therapy. Regular hematologic follow-up is required so that the drug may be stopped or dose modified as per the individual's needs.

Malignant gastrointestinal melanoma with an unknown primary.

Malignant melanoma is rare in India; melanoma presenting as a metastatic disease with an unknown primary, involving the gastrointestinal tract without involving lymph nodes is extremely uncommon. We report a case of a 28-year-old male with a malignant melanoma metastasizing to stomach and liver with an unknown primary. Relevant literature is being reviewed.

Leukemia as a second malignancy.

To study the occurrence of leukemia as a second malignancy following various primary solid and hematological malignancies. Total 11 cases of leukemia presenting as a second malignancy were studied over a period of 15 years from 1990 to 2005. The primary malignancies included carcinoma breast (4), multiple myeloma (3) and one each of Hodgkin's lymphoma, mediastinal germ cell tumor, papillary carcinoma thyroid and myxopapillary ependymoma. Ten patients had received chemotherapy with combination radiotherapy in six patients. The commonest type of leukemia was AML-M2. The cyogenetic test results were available in three cases. The secondary leukemia showed aggressive behaviour and all patients on follow-up died within a period of one month. The risk benefit ratio of chemotherapy and radiotherapy should be considered before starting the patients on treatment. A high degree of suspicion and follow up with hematological parameters is required for therapy related complications.

Extramedullary myeloid cell tumours--the NIMS experience.

Extramedullary myeloid cell tumours are rare clinical entities, which often pose diagnostic problems. From the pathology record files of Nizam's Institute of Medical Sciences, Hyderabad, 16 cases of EMCTs were traced, over a period of 14 years. The clinical details, follow-up were noted and morphology re-evaluated, and immunohistochemistry with LCA was performed. Of the 16 cases, the distribution was as follows--skin and subcutaneous nodules, lymph nodes, extradural masses presenting with cord compression and one case each with eyelid, orbital and breast masses. The problems in diagnosis are presented and a panel of immunohistochemical markers suggested for proper diagnosis and treatment.

Hodgkin's lymphoma presenting as extradural spinal cord compression.

OBJECTIVES: Hodgkin's lymphoma presenting with spinal cord compression is rare. Reports estimate that only 5% of patients with Hodgkin's lymphoma have spinal cord compression. The objectives of this study were:- (1) To review the histology of all cases of Hodgkin's lymphoma causing spinal cord compression. (2) To correlate the findings with the clinical details- lymphadenopathy, hepatosplenomegaly, and marrow involvement. METHOD: This was a retrospective study, the period of study being between 1987-2002. All cases were taken from the histopathology record files, pathology department, NIMS, Hyderabad. The clinical profile of each case was noted and the histology reviewed. When necessary, immunohistochemistry with the necessary markers was performed. RESULT: There were 12 cases, of which 11 were males, and one was a female. The patients ranged from 8-62 years of age, with a median age of 32 years. The cord involvement was at different levels- thoracic(8), lumbar(2) and cervical(2). CONCLUSIONS: The histologic diagnosis of Hodgkin's lymphoma presenting as cord compression requires awareness of the condition. The close differential diagnoses include non-specific inflammation, non-Hodgkin's lymphoma, tuberculosis and eosinophilic granuloma. Detailed clinical evaluation is essential for interpreting the histology.