Jatin S Gandhi

Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy

AIMS Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy. SETTINGS AND DESIGN We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA), and Epstein-Barr virus-encoded ribonucleic acid (EBER) studies via in situ hybridization (EBER-ISH). MATERIALS AND METHODS We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV)-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. RESULTS Common patterns included follicular hyperplasia only (five cases), mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases), completely atretic follicle (two cases), folliculolysis (11 cases), dumbbell-shaped follicles (three each), progressive transformation of germinal centers (four cases), T-zone expansion (two cases), Reed Sternberg (RS) cells like immunoblasts (two cases), Castlemans-like features with lollipop-like follicles (three cases) and a spindle cell prominence (one case). CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases). Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castlemans disease expressed EBER; however, they did not express HHV8. CONCLUSION The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective lymphadenitis, follicular lymphoma, Castlemans disease, progressive transformation of germinal center, Hodgkins disease and spindle cell neoplasms. Presence of EBV is common while HHV8 was not seen.

Clear cell adenocarcinoma of the male urethral tract.

We present a rare case of clear cell adenocarcinoma of the male bulbomembranous urethra. Mostly these tumors have been described in the female urethral tract with its possible origin from mullerian remnants, wolffian remnants or paraurethral glands. Histologically, these tumors have typically tubulocystic pattern comprising of hobnailed cells with clear glycogenated cytoplasm along with well-defined cytoplasmic membranes. This case is being presented due to its rarity, aggressive behavior and to discuss, trauma as its possible etiological factor.

Angioimmunoblastic T-Cell lymphoma: A critical analysis of clinical, morphologic and immunophenotypic features

BACKGROUND Angioimmunoblastic T-cell lymphoma (AITL), a subtype of peripheral T-cell lymphoma (PTCL), is characterized by unique clinical and biological features. Its diagnosis remains a challenge as clinical presentation as well as pathologic findings are frequently misleading. MATERIAL AND METHODS We retrospectively analyzed the clinical, morphological and immunophenotypic spectrum of 17 cases of histologically proven AITL. RESULT The mean age was 54 years and male to female ratio was 2.4. Common clinical features included generalized lymphadenopathy (60%), hepatomegaly (70%), splenomegaly (50%), anemia (80%) and polyclonal hypergammaglobulinemia (100%). Microscopically, three architectural patterns; pattern I (6%), pattern II (41%) and pattern III (53%) were observed. Bone marrow infiltration was seen in 60% cases and 30% cases revealed plasmacytosis. Absence of follicles, polymorphous infiltrate, extra-follicular follicular dendritic cell (FDC) proliferation, high endothelial venules (HEV) prominence and neoplastic T-cells were the diagnostic features of AITL. CD10 positivity (47%), clear cells in the background (59%) admixture with large size CD20+ B-immunoblasts (35%) and bone marrow plasmacytosis (50%) were common observations. CONCLUSION Awareness of various morphological and immunophenotypic complexities of AITL and distinction from reactive adenopathies and other types of lymphomas that mimic AITL is underscored in this study.

Urothelial carcinoma of bladder having rhabdoid differentiation with isolated scapular metastasis

Sir, Rhabdoid tumor was originally described by Beckwith and Palmer as a highly malignant renal tumor of childhood. Tumors with similar features have been documented in extra renal sites and also in adults. The histogenesis of these tumors is uncertain, however, electron microscopic studies in most cases have revealed cytoplasmic aggregates of intermediate filaments. Tumors with rhabdoid phenotype are associated with an aggressive clinical course. Urothelial carcinomas of bladder with rhabdoid differentiation are very rare and only handful of cases have been described in the literature. We present a case of urothelial carcinoma of bladder with prominent rhabdoid features in adult male with unusual distant bone metastasis to the acromian.

Low to intermediate grade salivary duct carcinoma associated with osteoclast like-giant cell tumor of parotid gland: A rare case with distinct pathological features

Osteoclast like-giant cell tumor of the salivary gland is an extremely rare tumor with distinct pathological features and unknown histogenesis. The neoplastic nature of these tumors in itself is questionable. We present the twentieth case in English literature of primary osteoclast like-giant cell tumor with accompanying low to intermediate grade salivary duct carcinoma of parotid gland, metastasizing to the ipsilateral cervical lymph node. As far as we know this is the second case with lymph node metastasis. Due to the rarity of the tumor its exact biological course is uncertain. We present and discuss this rare case with special emphasis on the histology, immunohistochemistry, and histogenesis.

Peri-ampullary collision tumor - high grade neuroendocrine carcinoma and signet ring cell carcinoma: A case report and review of literature

We report a case of 50-year-old male with obstructive jaundice diagnosed as peri-ampullary collision tumor comprising of large cell neuroendocrine carcinoma and signet ring cell carcinoma. The association of neuroendocrine (usually carcinoids) and adenocarcinoma is extremely uncommon with only few case reports available in the reported literature.

Isolated intrathyroidal metastasis revealing an occult lung adenocarcinoma

Thyroid gland is an uncommon site of tumor metastasis inspite of rich vascular supply. Most of the cases are picked up after the diagnosis or during the work up for the primary. Unexpected involvement of thyroid gland as the first presenting sign in a primary lung adenocarcinoma is an extremely rare, however, clinically significant finding, upstaging the disease. Fine needle aspiration cytology as a primary tool for detecting metastasis in thyroid is a rapid procedure, associated with high accuracy and low morbidity.

Radiation-induced chondrosarcomas: A case report with review of literature

Radiation therapy has become an important component of various cancer treatments. The development of second malignancy as a result of radiation therapy is a well-known sinister complication. However, radiation-induced sarcomas (RIS) are rare complications of radiation therapy. The timescale between completion of the radiotherapy and the development of a second malignancy, known as the latent period, can vary widely from as little as 5 years to 50 years later. Radiation-induced sarcomas per se are very rare and those with histomorphology of chondrosarcomas are even rarer. We report a rare case of RIS of left iliac bone in a 62-year-old lady after combined chemotherapy and external beam radiation therapy for cervical carcinoma (stage IIb). This case is being reported for its extreme rarity, vivid histology and clinical presentation.

Diagnostic Dilemmas in Aggressive Large B Cell Neoplasms with Enigmatic Immunohistochemical Profile: How Far Should We Investigate?

Aggressive large B-cell neoplasms include many disparate entities with marked differences in morphology, phenotype, molecular pathogenesis and clinical behavior, which affect the prognosis and require tailored therapy [1]. Differential diagnosis of plasmablastic lymphomas, from plasma cell myeloma with plasmablastic morphology, as well as Diffuse Large B-Cell Lymphoma (DLBCL) with secretory differentiation is still a common problem due to a lack of a distinctive phenotype [2]. Here, we report a case where multiple diagnostic modalities were applied in tandem to reach a conclusive diagnosis but still a consensus was difficult to achieve. A 46-year-old female presented with complaints of leftsided chest pain, radiating to the left subscapular region for one week and dyspnea for last 1–2 months. Physical examination was unremarkable. Complete hemogram showed HB = 97 g/L, TLC = 6.9x10/L with a differential count of N:40 L:46 M:011 Blast:01 My:01 PC:01; nRBC:4/100 WBCs and Platelet count = 83 9 10/L. Peripheral smear showed rouleaux formation with thrombocytopenia and occasional plasmacytoid cells. Serum calcium levels and renal function tests were within normal limits. Viral serology was negative. Skeletal survey showed no lytic/sclerotic lesions. Chest CT showed multiple nodules in bilateral lung upper lobes, paravertebral soft tissue masses, largest being at D4 para-vertebral region measuring 3.1 cm 9 2.6 cm and extending into left neural foramina, along with mild left pleural effusion. Magnetic Resonance Imaging of whole spine showed multiple para-vertebral soft tissue lesions with focal bony involvement and neural foramina compromise. A working clinico-radiological diagnosis of multiple myeloma was made and further work-up was advised. Serum LDH was 1158 U/L. Serum beta2-microglobulin level was markedly raised (1541.6 nmol/L). Serum protein electrophoresis showed a distinct M-band in the gamma region (15 g/L), which was found to be of IgA/kappa subtype on serum immunofixation studies. Bone marrow aspiration smears revealed near-total replacement of normal hematopoietic components by large atypical cells (65%) having high N/C ratio, prominent nucleoli and moderate amount of deeply basophilic cytoplasm with some of them showing eccentric nuclei. Bone marrow biopsy as well as the CT guided biopsy from D4 left para-vertebral soft tissue mass showed similar features comprising of diffuse proliferation of large neoplastic cells with central to eccentric, large hyperchromatic nuclei, few of them showing prominent nucleoli with brisk mitosis (Fig. 1). No intra-cytoplasmic or intranuclear inclusions were noted. Overall features were suggestive of a high grade Non Hodgkin Lymphoma (NHL) with plasmablastic differentiation and differential diagnosis included plasmablastic lymphoma, plasmablastic myeloma and DLBCLs with marked secretory differentiation. On IHC using primary backbone markers, these large neoplastic cells were strongly and diffusely positive for CD20, CD138, CD79A, bcl-2 and LCA with clonal restriction for kappa light chain(ISH) (Fig. 1). EBER expression (by ISH) was negative. In view of diffuse bone Disclaimers: The identity of the patient is not disclosed here in this case.

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.