Khushboo Dewan

Acute Lymphoblastic Leukemia with Normal Platelet Count

B-acute lymphoblastic leukemia (B-ALL) often presents with pancytopenia/bicytopenia, with thrombocytopenia being the most important parameter. The case of a 12-year-old child with bicytopenia on peripheral smear was presented. On bone marrow examination, 85% morphologically lymphoid blasts, negative for myeloperoxidase, and periodic-acid Schiff on cytochemistry were found. The blasts suppressed the erythroid population but not the megakaryocytic population. On flow cytometry, a diagnosis of common-ALL-antigen positive B-precursor ALL was concluded. To conclude, ALL cannot be excluded in patients who present with a normal platelet count. A bone marrow aspirate is crucial in patients with bi/pancytopenia.

Monitoring of Disease Activity in Chronic Myeloid Leukemia-chronic Phase Patients Treated with Indian Generic Veenat (NATCO) Imatinib Mesylate: A Tertiary Care Experience

Aim: Real-time quantitative polymerase chain reaction (RT-PCR) is a sensitive technique to monitor treatment response in chronic myeloid leukemia (CML). Standardization of RT-PCR protocols and interpretation of results are important to maintain the reliability of this molecular test. Methods: We present the analysis of treatment monitoring after administration of Indian generic imatinib mesylate (IM) (Veenat) in 73 patients with CML-chronic phase using RT-PCR. Results: A consistent decrease in the median breakpoint cluster region-abelson1 (BCR-ABL1) percentage denoting a continued time-bound response to IM is observed. At 6 months, 87.5% patients showing ≥ 1-log reduction in BCR-ABL1 levels subsequently developed ≥ 3-log reduction as compared to 42.8% patients showing < 1-log reduction. All patients with ≥ 3-log reduction in BCR-ABL1 at 12 months maintained treatment response at 18 months. Conclusion: The efficacy of Veenat (NATCO) is comparable to Gleevac (Novartis). Patients who attain ≥ 1-log reduction at 6 months and ≥ 2-log reduction at 12 months are more likely to subsequently attain a major molecular response.

Postmortem diagnosis of fulminant infectious mononucleosis

Fulminant infectious mononucleosis (FIM) is a rare but life-threatening complication of Epstein-Barr virus infection that usually affects immunodeficient individuals. It is a hyperinflammatory syndrome caused due to release of massive amount of various cytokines, leading to hemophagocytic lymphohistiocytosis on histopathology, and a plethora of clinical manifestations due to simultaneous involvement of multiple organs of the body. The case of a young male who presented with fever and dyspnea and died within 12 h of presentation to the hospital was taken for autopsy. The postmortem evidence of hemophagocytic lymphohistiocytosis in the spleen, bone marrow, lymph nodes, liver, and lungs and the presence of large, basophilic intranuclear inclusions that stained latent membrane protein-1 positive on immunohistochemistry led to the diagnosis of FIM.

Congenital presentation of a solitary superficial angiomyxoma in the parotid region masquerading as parotid tumor

Superficial angiomyxoma is a rare cutaneous and benign lesion. We present a case of congenital presentation of a superficial angiomyxoma in the parotid region in a 9-year- old female that was misdiagnosed as a parotid tumor. Appropriate diagnosis is important since such lesions have a good prognosis and rarely affect deeper structures. Possibility of superficial angiomyxoma should be kept in mind in the differential diagnosis of lesions of the parotid region.

Analysis of epithelial-cadherin and human epidermal growth factor receptor 2/ expression in gastric carcinoma using immunohistochemistry

CONTEXT Gastric adenocarcinoma (GAC) is a common malignancy with high mortality-rate. Analysis of molecular markers could form a foundation for the future use of targeted therapies to reduce morbidity and mortality. AIMS To find the prevalence and relation of epithelial cadherin (E-cadherin) and human epidermal growth factor receptor 2 (HER-2/neu) protein expression with histological type and grade of GAC using immunohistochemistry (IHC). MATERIALS AND METHODS A total of 100 cases of GAC diagnosed over a 2 year period were studied. Expression of E-cadherin and HER-2/neu was analyzed by IHC in relation to the histological type and grade. RESULTS Of the 100 cases of GAC studied, 11 revealed a loss of E-cadherin and over-expression of HER-2/neu was seen in 17 cases. Loss of E-cadherin was seen in 50% of signet ring-cell carcinomas but only in 8% of tubular and none of papillary and mucin-secreting GAC (P = 0.003). Of all the cases of tubular GAC with loss of E-cadherin expression, majority (71.4%) were Grade III (P = 0.04). Of all the tubular GAC cases with an over-expression of HER-2/neu, 20% and 67% were Grade I and II GAC respectively while only 13% were Grade III (P < 0.001). CONCLUSIONS Although poorly-differentiated tumors show loss of E-cadherin, better-differentiated tumors over-express HER-2/neu protein. Signet ring-cell carcinoma is more likely to exhibit a loss of E-cadherin protein. Targeted therapy toward HER-2/neu in GAC should be considered. Novel therapy to block E-cadherin down-regulation is justified.

Squamous cell carcinoma with osteoclast-like giant cells masquerading as pleomorphic sarcoma: A rare case report

Squamous cell carcinoma (SCC) with osteoclast-like giant cells (OLGCs) is a rare entity known to occur in skin, breast, lung, and pharynx. Only a single case of SCC containing OLGC in larynx has been reported so far. We report a case of a 65-year-old male patient presenting with sudden onset respiratory distress, who was subjected to biopsy, which was reported as undifferentiated sarcoma which was endorsed on laryngectomy specimen, however, sections from cervical lymph nodes revealed deposits of SCC. Extensive resectioning revealed a single focus showing origin of poorly differentiated carcinoma from the overlying squamous epithelium. Hence in undifferentiated pleomorphic sarcoma, a thorough sectioning and careful search for SCC including immunohistochemical markers should be done to exclude the possibility of a poorly differentiated epithelial malignancy.

Comparing flow cytometry immunophenotypic and immunohistochemical analyses in diagnosis and prognosis of chronic lymphoproliferative disorders: Experience from a Tertiary Care Center

Background: The latest World Health Organization classification incorporates extensive description of immunophenotype of the neoplastic cells while describing chronic lymphoproliferative disorders (CLPDs). The present study was undertaken with an aim to identify and compare the roles of flow cytometry (FCM) and immunohistochemistry (IHC) as modalities of immunophenotyping in the diagnosis of CLPDs. Materials and Methods: Thirty untreated cases of CLPDs were enrolled in the study. Twenty eight cases of B-CLPD were divided into two groups - chronic lymphocytic leukemia (CLL) (21 patients) and non-CLL (7 patients). Peripheral blood/bone marrow aspirate samples were analysed by FCM using various panels of monoclonal antibodies. Immunohistochemical analysis of bone marrow biopsies obtained from these patients was also performed. Results: Panel A of monoclonal antibodies comprising CD5, CD23, CD22, surface membrane immunoglobulin (SmIg), FMC7 and Panel B comprising CD5, CD23, CD22, SmIg, FMC7, CD79b were useful (P < 0.01 and <0.001 respectively) while Panel C comprising CD5, CD23, SmIg, FMC7 and CD79b was not found to be useful in distinguishing CLL from non-CLL (P > 0.05) The concordance rate between FCM and IHC ranged from 80% to 100% for all comparable immunological markers. In all cases of CLPDs, we propose a screening panel comprising 9 markers including CD19, CD5, CD23, FMC7, CD10, CD20, CD3, kappa and lambda, which are important for specifying the lineage (B or T), to differentiate CLL from non-CLL group and for deciding the secondary panel. Conclusion: Scoring system using CD5, CD23, CD22, FMC7, CD79b, and SmIg is useful in differentiating CLL from non-CLL cases. Concordance rate of FCM and IHC in CLPDs is 93.3%. Using a panel comprising CD19, CD5, CD23, FMC7, CD10, CD20, CD3, kappa and lambda, a diagnosis of CLL, mantle cell, and follicular lymphoma, the three most common CLPDs can be made. Secondary panels for diagnosis of hairy cell leukemia and T-cell CLPD should be utilized.

Standardization of real-time quantitative polymerase chain reaction for detection of the JAK2V617F mutation in BCR-ABL1 negative myeloproliferative neoplasms: A tertiary care centre experience

Background: Identification of JAK2V617F mutations has led to a significant development in our understanding of the pathogenesis and therapy of BCR-ABL1 negative myeloproliferative neoplasms (MPNs). However, not all cases of BCR-ABL1 negative MPNs carry JAK2V617F mutations. The present study was undertaken with an aim to standardize the real-time quantitative polymerase chain reaction (PCR) for the detection of JAK2V617F mutations and to find the prevalence of Janus kinase 2 (JAK2) mutations in MPNs in the Indian scenario. Materials and Methods: Real-time quantitative PCR was used to detect the JAK2V617F mutation. Standardization of the detection procedure was carried out using recommended guidelines to ensure the accuracy and reproducibility of results. Forty-nine patients of BCR-ABL1 negative MPNs were included in the study. Results: The JAK2V617F mutation was detected in 63.3% patients of BCR-ABL1 negative MPNs. On classification of these BCR-ABL1 negative MPNs, JAK2V617F mutation was detected in 78.3% patients with polycythemia vera (PV), 62.5% patients with essential thrombocythemia (ET), and 44.4% patients with Primary myelofibrosis (PMF). Conclusion: Role of detection of JAK2 mutations in BCR-ABL1 negative MPN has begun to be described and can be used in the diagnosis of PV, ET, and PMF along with other criterias. In future, it may be suitable for treatment monitoring and prognostication.

Primitive neuroectodermal tumor in a mixed germ cell tumor - A rare case report

A rare case of testicular tumor in a 20-year-old male with Primitive Neuroectodermal Tumor (PNET) was reported. Imaging studies showed a large heterogenous mass in the right scrotal sac and a large retroperitoneal mass with metastasis in the lung and liver. Serum alpha fetoprotein (AFP) was markedly elevated with moderate increase in serum β-human chorionic gonadotropin (hCG) levels. After orchidectomy, a histological diagnosis of mixed germ cell tumor-teratoma with primitive neuroectodermal, embryonal, and yolk sac components was made. Some scattered embryoid bodies representative of primitive germ cell tumor were also present. Morphological diversity including PNET prompted the authors to report this case as PNET points toward a poor prognosis.

Sweet's Syndrome in Acute Lymphoblastic Leukemia with t (9:22)

Sweet′s syndrome (SS) is a rare disease diagnosed in children and is characterized by fever, erythematous skin lesions, and dense infiltration of neutrophils in the upper dermis without evidence of leukocytoclastic vasculitis on histopathology. It may occur secondary to infection, malignancy or drug intake. A case of a 9-year-old boy diagnosed as acute precursor B-cell lymphoblastic leukemia with BCR-ABL1 mutation and treated with induction chemotherapy and imatinib mesylate (IM) therapy is presented. After 8 weeks of consolidation chemotherapy, the patient developed painful and erythematous nodules where a biopsy showed dense neutrophilic infiltrate and edema in the papillary dermis consistent with SS. Whether SS is caused clinically by acute lymphoblastic leukemia, the presence of BCR-ABL1 mutation or due to IM therapy is discussed.