Primary extranodal non-Hodgkin lymphoma: A 3-year record-based descriptive study from a tertiary care center in Southern India.

Introduction: Primary extranodal lymphoma (pENL) refers to group of disorders arising from tissues other than lymph nodes and even from sites, which normally do not contain lymphoid tissue. This study was undertaken to ascertain the prevalence, anatomical distribution, and histological subtypes of extranodal non-Hodgkin lymphoma (NHL) from a tertiary care institute in Southern India. Materials and Methods: This was a cross-sectional study conducted in the Department of Pathology over a period of 3-years. Detailed clinical history, routine complete blood count, microbiological status was obtained from the medical records. Hamatoxylin and eosin slides were reviewed and immunohistochemistry was performed using a panel of antibodies depending on the morphology. All cases were classifi ed based upon morphologic and immunophenotypic criteria according to World Health Organization 2008 classifi cation. Results: Primary extranodal NHL constituting 22.6% (68/300) of all NHL and the majority of patients were from higher age group with peak incidence seen in fourth to fi fth decade of life. In the pediatric population, the most common site is ileocaecal region (42.8%) and the most common morphology is lymphoblastic lymphoma (42.8%). Similarly in the adult population head and neck was the most common site constituting 36% and diffuse large B-cell lymphoma is the most common morphological subtype comprising 54% of all extranodal lymphomas. Conclusion: Although the reported incidence of pENL is low in India compared to other parts of the world, the possibility of pENL should always be kept in mind even though it arises in an extranodal site.

Spectrum of histopathologic diagnosis of lymph node biopsies: A descriptive study from a tertiary care center in South India over 5½ years.

Aims: Lymphadenopathy is a common clinical problem and biopsies undertaken to determine the cause of nodal enlargement may be neoplastic or nonneoplastic. The former are mainly lymphohematogenous malignancies and metastases while the causes of non-neoplastic lymphadenopathy are varied. This study was undertaken to determine the histopathological spectrum of lymphadenectomies. Materials and Methods: This was a descriptive crosssectional study wherein 1010 cases of histologically diagnosed peripheral lymph node biopsies in the Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry from January 2007 to June 2012 were reviewed. Surgical resection specimens with lymph node dissection were excluded from the study. Results: Neoplastic lesions were more common comprising 53% (535 cases) and included 32.1% (324 cases) of non-Hodgkin lymphoma, 12.4% (125 cases) of Hodgkin lymphoma and 8.5% (86 cases) of metastatic lesions. The non-neoplastic lesions were 47% (475 cases), which included 21.6% (218 cases) of non-specifi c reactive lymphoid hyperplasia, 6.8% (69 cases) of other reactive or specifi c lymphoid hyperplasia, 18% (182 cases) of tuberculous lymphadenitis, 0.6% (6 cases) of other granulomatous lesions. Conclusions: Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. Among the biopsied nodes, lymphomas were the most common (44.5%) followed by non-specifi c reactive hyperplasia (21.6%), tuberculous lymphadenitis (18%) and metastasis (8.5%).

Nodal mantle cell lymphoma: A descriptive study from a tertiary care center in South India.

Introduction: Mantle cell lymphoma (MCL) is a type of B-cell non-Hodgkin lymphoma (NHL) with distinctive morphologic, immunophenotypic and a characteristic cytogenetic abnormality, the t(11;14)(q13;q32) and overexpression of cyclin D1. The common histologic features include effaced lymphoid architecture by a monomorphic lymphoid population with a vaguely nodular, diffuse or mantle zone growth pattern. The classic cytomorphologic features include small to medium sized lymphoid cells with irregular nuclear contours and scanty cytoplasm, closely resembling centrocytes. Materials and Methods: This retrospective study comprises 13 cases of MCL over a period of 5½ years in our department, comprising 4% of all nodal NHL diagnosed. All cases were diagnosed on lymph node biopsy. Results: The mean age of the presentation was 57 years. There was a male preponderance (M:F = 2.25:1). The disease was nodal in all cases. Most patients (84.5%) had generalized lymphadenopathy and/or hepatosplenomegaly. Bone marrow involvement was seen in 81.8% of cases. Three cases showed a nodular pattern on lymph node biopsy while remaining ten had a diffuse pattern. Immunophenotyping showed positivity for CD20, CD5 and cyclin D1 and CD23 negativity. Conclusion: Despite certain morphological similarity to other low-grade/intermediate-grade lymphomas, MCL has a characteristic appearance of its own. Since it is more aggressive than other low-grade lymphomas it needs to be accurately diagnosed.

Low grade follicular lymphoma with high proliferation index; diagnostic and management issues.

Follicular Lymphoma (FL) is the second most common B-Non Hodgkin Lymphoma after diffuse large B cell lymphoma (DLBCL). Low grade FL is known for its indolent behavior; however, one subset of FL behave aggressively and may require intensive therapy. One of the diagnostic issues in FL is to identify this subgroup of cases. Proliferation index can have prognostic importance in this subset of cases. We discuss one case of low grade FL with a paradoxically high proliferative index. A 63 year male presented with generalized lymphadenopathy of one year duration, which was gradually increasing in size. On examination, patient had bilateral cervical, axillary and inguinal nodes. Biopsy of the left cervical lymph node was reported as FL - Grade 2, with high proliferative Index (60%). The patient was put on CHOP regimen targeted for high grade lymphomas, and had complete remission. High proliferative index in FL is a poor prognostic factor irrespective of the histologic grade. So, proliferative index should be assessed in all cases of FL as an adjunct to histologic grading.

Clinico-hematological profile of Chediak-Higashi syndrome: Experience from a tertiary care center in south India.

Introduction: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by partial ocular and cutaneous albinism, increased susceptibility to pyogenic infections, the presence of large lysosomal-like organelles in most granule-containing cells and a bleeding tendency. The abnormal granules are most readily seen in blood and marrow leukocytes, especially granulocytes; and in melanocytes. Other clinical features include silvery hair, photophobia, horizontal and rotatory nystagmus and hepatosplenomegaly. Materials and Methods: The clinico-hematological profile of a series of 5 cases of CHS encountered at JIPMER Hospital with diagnostic work-up done in the Department of Pathology over the last 6 years is presented. The diagnostic work-up included complete hemogram with peripheral smear, bone marrow examination, skin and liver biopsies. Results: The age of the patients ranged from 5 months to 3 years. All patients had silvery hair and partial albinism and presented with fever and recurrent chest infection. Two patients were stable. Three patients were in accelerated phase; of them, 1 patient with associated hemophagocytic syndrome had a rapidly fulminant course. Peripheral blood smear showed anomalously large granules in the leukocytes. Skin biopsy showed sparse, coarse melanin pigment in the epidermis, and liver biopsy done in 2 patients with accelerated phase showed portal lymphohistiocytic aggregates. Conclusions: The diagnostic hallmark of CHS is the occurrence of giant inclusion bodies (granules) in the peripheral leukocyte and their bone marrow precursors. The case series is being presented because of the rarity of CHS and varied spectrum of clinical and hematological presentation.

Palmar cutaneous metastasis from carcinoma cervix.

Carcinoma of the uterine cervix is the most common gynecological malignancy in developing countries. However, its cutaneous metastasis is a rare entity. The reported incidence of cutaneous metastasis ranges from 0.1 to 2%. Frequent sites of cutaneous metastasis in decreasing order are: abdominal wall, vulva and anterior chest wall. To the best of our knowledge, only three cases of cutaneous metastasis to the upper extremity have been reported in the world. We report a case of a 74-year-old postmenopausal lady diagnosed to have carcinoma cervix (stage IIIB) who presented with cutaneous metastasis to palm and thigh, 10 months after radical radiotherapy. At presentation, the primary disease had resolved completely. She had a small nodular growth in the left palm and left thigh. Fine needle aspirate cytology and core needle biopsy from both the nodular lesions were positive for squamous cell carcinoma.

Role of melatonin against oxidative tissue damage induced by Cleistanthus collinus in rat brain.

Background & objectives: The leaves of Cleistanthus collinus, an extremely poisonous plant are consumed for suicidal purposes in various parts of India. The mortality rate is high and there is no antidote. In this study, we attempted to delineate oxidative stress as a possible mechanism of action of C. collinus toxicity in rats and the role of melatonin against injury to brain and heart caused by C. collinus. Methods: Adult Wistar rats (130 -200 g, n = 6 per group) of either sex were used. C. collinus at 8 mg/kg body weight (LD50) was administered orally followed by melatonin 15 mg/kg body weight ip or cysteine 500 mg/kg body weight ip (standard) after 2 h. Malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase and catalase levels in brain, heart and blood were estimated and histopathological examinations (brain and heart) were done. For the survival study, rats were treated with increasing doses of melatonin (5, 10 and 15 mg/kg body weight ip) following a lethal dose of C. collinus (10.5 g/kg body weight orally). Results: The results showed a significant (P<0.05) increase in blood and brain MDA levels and decrease in tissue GSH in the LD50 group. This was accompanied by marked gliosis, spongiform necrosis and lymphocytic inflammatory infiltrates in brain and marked congestion, inflammation and muscle necrosis in heart. Melatonin significantly (P<0.05) reduced lipid peroxidation and reversed the histopathological changes induced by C. collinus in the brain but not in the heart. Interpretation & conclusion: Our results suggest that oxidative mechanisms play an important role in C. collinus induced tissue damage and melatonin, by balancing oxidant-antioxidant status ameliorates oxidative organ injury in brain due to C. collinus toxicity.

Immunohistochemical distinction between mesothelial and adenocarcinoma cells in serous effusions: a combination panel-based approach with a brief review of the literature.

BACKGROUND: The prognostic and therapeutic significance of differentiating adenocarcinoma (AC) from reactive mesothelium (RM) in effusions cannot be overemphasized. To avoid diagnostic errors, ancillary techniques like immunohistochemistry are employed. However, results vary and no universal standard has been accepted so far. OBJECTIVE: To study the combined diagnostic efficacy of epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), E-cadherin (EC), calretinin (CAL), desmin (DES) and vimentin (VIM) in distinguishing RM from AC cells in serous effusions. STUDY DESIGN: Unequivocally diagnosed cases of 39 adenocarcinomatous and 38 RM populations were studied using sections from 49 formalin-fixed, paraffin-embedded cell blocks. MATERIALS AND METHODS: The immunomarkers were applied on cell block sections using the avidin-biotin peroxidase technique. The distribution/intensity of immunostaining in mesothelial and AC cells were graded semiquantitatively. STATISTICAL ANALYSIS USED: Fischer's exact test was used to calculate the efficacy of individual markers and their combinations. RESULTS: EMA was the best single marker for AC, with 100% sensitivity and 97.37% specificity. For the mesothelial cells, CAL exhibited 100% sensitivity and 92.31% specificity. DES was more specific than CAL but had a poor sensitivity of 55.26%. EC, CEA and VIM had unsatisfactory predictive values precluding their use as individual diagnostic markers. Among the combinations, two panels--EMA+ AND (CAL- OR DES-) for ACs and CAL+ AND (EMA- OR CEA-) for RM had 100% specificities and sensitivities. CONCLUSIONS: Most panel studies on fluid cytology are based on the arbitrary use of individual markers with the best statistical values, leading to a less than accurate diagnostic assessment. We believe that statistical parameters calculated in combination provide for a more practical and objective evaluation as well as allowing for meaningful comparative studies.

Osseous metaplasia in renal cell carcinoma: report of a rare case.

Focal calcifications are frequently seen in renal masses including renal cell carcinoma (RCC). Osseous metaplasia, on the other hand, is a rare finding in RCC. We report a case of RCC with radiological evidence of speckled calcification that showed osseous metaplasia on histopathological examination. The clinical and pathologic differential diagnosis for this tumor is discussed along with a review of the literature on this unusual phenomenon.

Role of bone marrow trephine biopsy in the diagnosis of marrow involvement in Hodgkin's disease.

Bone marrow involvement in Hodgkin's disease alters the stage and hence the prognosis and treatment modality. Seventy-six patients of biopsy proven Hodgkin's disease in whom a bone marrow aspiration and biopsy were done simultaneously at the time of diagnosis were included in the study. Bone marrow involvement was seen in 14 (18%) cases. All 14 cases were diagnosed on biopsy. Only one aspirate was suspicious of involvement. Rest was either diluted (28%) or was normal (64%). Eleven patients were upstaged from stage I, II and III to stage IV. All patients had cytopenia of one or more cell line. Increased fibrosis, necrosis and a polymorphic cellular infiltrate were associated findings in the marrow. We wish to highlight the importance of bone marrow trephine biopsy over aspirate in staging even clinically early stage Hodgkin's disease.

Fetus in fetu or differentiated teratomas?

Two cases of congenital teratoma were operated upon. In view of the high degree of organoid differentiation of the teratomas with rudimentary limbs, intestine, brain-like and pulmonary tissues, it was difficult to distinguish it from fetus-in-fetu. In the light of the data obtained and extensive review of related literature, we consider that fetus-in-fetu and teratoma may not be unrelated entities. Our cases support the view held that fetuses in fetu are highly differentiated teratomas.

Immunohistochemical typing of non-Hodgkin's lymphoma-comparing working formulation and WHO classification.

The recent WHO classification of non-Hodgkin's lymphoma is based on the morphology and immunohistochemical expression of the lymphoma cells and to a lesser extent, on the molecular and cytogenetic findings. Fifty-three cases of non-Hodgkin's lymphoma were included in the study. Of these, seven cases were primary extra nodal lymphomas. Twenty two patients had peripheral blood and/or bone marrow involvement. A detailed morphological assessment was done and classified using the International working formulation. The two most common types encountered were diffuse large cell lymphoma and small lymphocytic lymphoma. Immunohistochemistry was done using labeled streptavidin-biotin peroxidase complex with CD3, CD20, CD15, CD30, CD 45 (leukocyte common antigen), Cyclin D1, EMA (epithelial membrane antigen). 38 cases (72%) showed B cell expression and 12 cases (22.5%) showed T cell expression. Three cases did not express either marker. B-cell diffuse large cell lymphoma (26%) was found to be the predominant B cell non-Hodgkin's lymphoma. The commonest T-cell lymphoma was T lymphoblastic lymphoma (67%) followed by peripheral T cell angioimmunoblastic lymphoma (25%). Immunohistochemistry is a useful and necessary diagnostic modality and helps subdivide prognostically different types of non-Hodgkin's lymphoma.

Immunophenotyping of Hodgkin's disease--an aid to its classification.

Based on morphological, phenotypic, genotypic and clinical findings, Hodgkin's disease has recently been classified into two subtypes: Nodular lymphocyte predominant and classical Hodgkin's disease. Forty-two cases of Hodgkin's disease were subjected to detailed morphological assessment and immunophenotyping. The commonest subtype was Nodular Sclerosis seen in 27 cases. The panel of antibodies used was CD 15, CD 30, CD 3, CD 20, CD 45 and Epithelial Membrane Antigen. Immunophenotyping was done by Streptavidin Biotin Peroxidase complex technique. CD 30 was expressed in 86% and CD 15 in 76% cases. Immunophenotype helped reclassify two cases, according to the WHO classification scheme. Although morphology remains the gold standard in the diagnosis of Hodgkin's disease, immunophenotype is a useful adjunct in differentiating prognostically distinct subtypes.

Interfollicular Hodgkin's disease: an uncommon pattern that may cause diagnostic difficulty.

Interfollicular Hodgkin's Disease is characterised by reactive follicular hyperplasia with involvement of the interfollicular area of lymph node by Hodgkin's lymphoma. It represents a peculiar pattern of focal involvement of lymph node and does not constitute a classical subtype. Its importance rests in the fact that it can be misinterpreted as one of the many causes of reactive hyperplasia of lymph node and not as Hodgkin's disease. Eleven cases of interfollicular Hodgkin's disease were diagnosed in a period of five years. Majority of the patients were less than twenty years and all had localised lymphadenopathy. Lymph node biopsy showed follicular hyperplasia with expanded interfollicular area. Careful search of the interfollicular area showed infiltration by inflammatory cells and scattered Reed-Sternberg and Hodgkin's cells. Immunohistochemistry with CD 15 and CD 30 highlighted the atypical cells. This report emphasises on the problems in diagnosis of interfollicular Hodgkin's disease.

Angioimmunoblastic T-cell lymphoma obscured by concomitant florid epithelioid cell granulomatous reaction--a case report.

Epithelioid cell granuloma occurs in association with many neoplasms including lymphoma. However they have rarely obscured the microscopic features of a lymphoma. We report on a case where a florid epithelioid cell granulomatous reaction caused difficulty in interpretation and delayed the final diagnosis of a case of peripheral T cell lymphoma of the angioimmunoblastic type. We draw attention to this unusual phenomenon because of its practical implications.

Granulomas in bone marrow--a study of fourteen cases.

Granulomas in bone marrow are an infrequent finding and several diseases are associated with granuloma formation. Clinicopathological details of fourteen cases showing granulomas in bone marrow were studied. Fever was the commonest clinical presentation and anaemia was seen in all cases. Only one case showed epithelioid cells in the bone marrow aspirate smear while trephine biopsy was diagnostic in all cases. Granulomas were seen mainly in the paratrabecular space. Acid fast bacilli were demonstrated in five biopsies and serological test for Human Immunodeficiency virus was positive in five cases. Tuberculosis was more common in the present study as compared to others, probably due to the endemicity of tuberculosis in this region. Bone marrow biopsy is useful in the investigation of pyrexia of unknown origin as it leads to an aetiological diagnosis in most cases.

Value of nucleated red blood cells in predicting severity and outcome of perinatal asphyxia.

The objective of the study was to assess nucleated red blood cell counts in cord blood in a group of asphyxiated infants, and to determine its predictive value for short-term outcome. A prospective case control study was undertaken on cord blood samples collected from fifty six term neonates with perinatal asphyxia and an equal number of normal appropriately matched controls for cord blood pH and nucleated RBC counts. Babies were followed up in nursery till discharge. Statistical analysis employed were ANOVA test, logistic and linear regression analysis. There was a significant increase in the number of nucleated red blood cells in cases as compared to controls. Low Apgar, cord blood pH and neonatal outcome correlated well with nucleated RBC counts. Nucleated red blood cell count at birth is a useful predictor of severity and short-term outcome of perinatal asphyxia.

Lymphoplasmacytic lymphoma with IgA paraproteinemia mimicking Waldenstrom's Macroglobulinemia.

Central to the diagnosis of Waldenstrom's Macroglobulinemia is the demonstration of bone marrow infiltration by lymphoplasmacytic lymphoma with Ig M monoclonal gammopathy. We describe a patient who presented with a clinical and haematological picture, highly suggestive of Waldenstrom's Macroglobulinemia, but whose serum monoclonal immunoglobulin belonged to Ig A class. Ig A secreting lymphoplasmacytic lymphoma undoubtedly exist but are exceedingly uncommon and their relationship to Waldenstrom's Macroglobulinemia needs to be clarified.