An immunohistochemical study of diffuse large B-cell lymphoma with molecular subtyping based on Hans algorithm.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma accounting for about 40% of all lymphomas. The international prognostic index (IPI), which relies on clinical and laboratory parameters, is used as a prognostic tool in DLBCL. In this study, we have included cases of DLBCL not otherwise specified (NOS) type to test the usefulness of the biological subclassification of DLBCL by immunohistochemistry (IHC) using the Hans algorithm into the germinal center B-like (GCB) type and nongerminal center (non-GCB) type. We correlated the subtypes with the demographics, site of involvement, IPI scores, and stage. OBJECTIVES: 1. To study the immunohistochemical profile of DLBCL. 2. To classify patients with DLBCL into germinal center and nongerminal center subtypes. 3. To review the clinical presentations, clinical staging, and follow-up data in cases of DLBCL. MATERIALS AND METHODS: A total of 152 cases of DLBCL reported from January 2010 to March 2018 were included in this study. Clinical data, treatment details, and follow-up were reviewed. Apart from the routine IHC markers for DLBCL, additional markers CD10, BCL6, and MUM 1 were performed to classify DLBCL into GCB type and non-GCB type using the Hans algorithm. RESULTS: The median age of presentation was 53 years with male-to-female ratio of 2:1. Most of the patients presented with nodal involvement (56.6%); cervical lymph node is the most common site (46.5%). The majority of the patients presented in Ann Arbor stage 1 (44.8%). According to the international prognostic index, 34.8% had a score of 3 (high intermediate). After IHC studies, GCB subtype (51.5%) of DLBCL emerged as more common than non-GCB type (48.5%). The two subtypes differed significantly with regard to sex (i.e. GCB type was more common in males and non-GCB type in females) and showed no significance with regard to any of the other clinical features and prognostic parameters evaluated. CONCLUSION: Our study showed that IHC was a useful tool to subclassify DLBCL into GCB and non-GCB subtypes and may be easily incorporated in routine clinical practice.

Lymph node yield in colorectal cancer specimens and its impact on pathological staging: Does number matter?

Introduction: Regional lymph node involvement is an important predictor of outcome in colorectal cancer (CRC). The lymph node yield in resected specimens varies from case to case. Aim: To assess whether clinicopathologic factors have an impact on the number of lymph nodes harvested from surgical resection specimens of CRCs To assess whether the total number of lymph nodes retrieved has a bearing on the positivity of lymph nodes and hence the N category. Materials and Methods: All resection specimens of treatment naïve CRC received in the department of pathology during a 2 year period (2017-2019) were reviewed. The lymph node yield was correlated with age, sex, type of surgical procedure, length of resected segment, tumor location, histological type and grade, T and N categories. The statistical tests used were Spearman rank, Mann-Whitney U, Kruskal-Wallis, and Chi-square tests. Results: A total of 51 resections were studied. The mean age was 59.64 years with 72.55% being male. About 76.47% were hemicolectomies and 23.52% were rectosigmoid surgeries. The lymph node yield ranged from 0 to 38, the mean being 12.67. None of the parameters studied had a significant correlation with the lymph node yield except histological grade, specimens with higher-grade tumors yielding more number of nodes (P = 0.0242). There was no significant correlation between node positivity and the average number of lymph nodes (P = 0.0883). There was no significant correlation between total yield in cases with ≥12 lymph nodes and N category (P = 0.180). Furthermore, there was no significant correlation between total yield in node-positive cases with ≥12 lymph nodes and N category (P = 0.216). There was no significant difference in the sizes of the lymph nodes in node-positive and negative cases (P = 0.3930 and 0.2355, respectively). Conclusion: Among the parameters affecting lymph node yield, the current study found a significant correlation between histological grade and lymph node yield. There was no significant difference in the size of lymph nodes between node-positive and negative cases. The total lymph node yield did not have a bearing on node positivity and this shows that a lower lymph node yield may be accepted as adequate after thorough examination of the specimen.

An immunohistochemical study of double-expressor lymphomas and its correlation with cell of origin.

Background: Diffuse large B cell Lymphomas (DLBCL) that co express C MYC and BCL 2 are known as 'double expressor lymphomas' and are believed to have a worse prognosis than other diffuse large B cell lymphomas. This was a study to assess the frequency of double expressor lymphomas in our cohort of DLBCL. Aims and Objectives: The aims of this study were to assess the frequency of double expression of C MYC and BCL 2 in cases of DLBCL and to correlate the same with clinicopathological parameters including cell of origin, namely germinal centre type versus non germinal centre type. Materials and Methods: This was a retrospective observational study Immunostaining for MYC antibody and BCL2 were performed using the standard polymer/DAB technique. 40% for MYC and 50% for BCL2 were taken as cut off values.Chi square analysis was used to compare the variables, and a p value of less than 0.05 was taken as statistically significant. Results: Of 40 cases studied, 11 (27.5%) were double expressors. There was no significant correlation of double expression with gender, site (nodal versus extra nodal), cell of origin namely germinal centre/non germinal centre types and Ki67 index when compared to the other group which did not show double expression. Conclusions: Immunohistochemistry is a useful technique to detect double expressor lymphomas which are known to have an aggressive course. Cell of origin did not show significant correlation with double expression in our study.

Unique diagnostic challenge in surgery: hepatic abscess versus malignancy.

A man in his 30s had presented with a history of abdominal pain, vomiting and high-grade fever. He had tender hepatomegaly with peritonism in the upper abdomen. Investigations revealed a neutrophilic leucocytosis, and contrast-enhanced CT had shown several well-defined peripherally enhancing thick-walled cystic lesions with non-enhancing centres throughout the liver suggestive of pyogenic liver abscess, treated initially with antibiotics. However, ultrasonography-guided fine needle aspiration revealed atypical neoplastic cells, and a trucut biopsy showed squamous cell carcinoma (SCC). He developed acute shortness of breath. CT pulmonary angiogram confirmed pulmonary thromboembolism (PTE). Incidentally, here we saw a solitary nodule in the right middle lobe, probably a neoplastic lesion. His condition deteriorated rapidly secondary to PTE and died. A pathological review was positive for CK7, p40, p63 and CK19 confirming SCC. We concluded the primary was a pulmonary SCC with multiple hepatic metastases. Hepatic metastases can mimic an abscess; trucut biopsy with immunohistochemistry was critical for a definitive diagnosis.

SARS-CoV-2 infection of human-induced pluripotent stem cells-derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the lung, particularly the proximal airway and distal alveolar cells. NKX2.1+ primordial lung progenitors of the foregut (anterior) endoderm are the developmental precursors to all adult lung epithelial lineages and are postulated to play an important role in viral tropism. Here, we show that SARS-CoV-2 readily infected and replicated in human-induced pluripotent stem cell-derived proximal airway cells, distal alveolar cells, and lung progenitors. In addition to the upregulation of antiviral defense and immune responses, transcriptomics data uncovered a robust epithelial cell-specific response, including perturbation of metabolic processes and disruption in the alveolar maturation program. We also identified spatiotemporal dysregulation of mitochondrial heme oxygenase 1 (HMOX1), which is associated with defense against antioxidant-induced lung injury. Cytokines, such as TNF-α, INF-γ, IL-6, and IL-13, were upregulated in infected cells sparking mitochondrial ROS production and change in electron transport chain complexes. Increased mitochondrial ROS then activated additional proinflammatory cytokines leading to an aberrant cell cycle resulting in apoptosis. Notably, we are the first to report a chemosensory response resulting from SARS-CoV-2 infection similar to that seen in COVID-19 patients. Some of our key findings were validated using COVID-19-affected postmortem lung tissue sections. These results suggest that our in vitro system could serve as a suitable model to investigate the pathogenetic mechanisms of SARS-CoV-2 infection and to discover and test therapeutic drugs against COVID-19 or its consequences.

Chronic granulomatous 'Aspergillus lung mass'.

The diverse clinicopathological spectrum of pulmonary aspergillosis is a consequence of varying levels of invasiveness of this ubiquitous fungus, which largely depends on the host immune response and pre-existing lung disease. The clinical presentation of pulmonary aspergillosis spans a wide spectrum from hypersensitivity to life threatening angio-invasive and disseminated disease. We report the case of a young immunocompetent male with no underlying lung disease, who presented with an incidentally detected 'infective mass' lesion in the lung associated with minimal respiratory symptoms. The diagnostic challenges posed by the unusual clinical, radiological and histological picture as well as the therapeutic dilemmas faced are discussed in this report.

Perception of pathology as a career among undergraduate medical students.

Background: The choice of a postgraduate specialization in medicine is influenced by many factors. What motivates students to take up pathology as a career option or to reject the same remains unexplored. This study aimed to understand the perceptions of medical students from a college in southern India regarding the role played by pathologists in clinical practice and how this influenced their choice of pathology as a career. Methods: This qualitative study conducted personal interviews with 15 participants (13 undergraduates and 2 postgraduates in pathology) using a semi-structured interview guide. The data were transcribed and thematically analysed. Results: Although most of the participants acknowledged that pathologists play an important role in diagnosis, they were of the view that pathologists have minimal patient contact and do not play the main role in treating patients. They were also of the opinion that the undergraduate course and curriculum in pathology was inadequate in exposing them to the actual practice of pathology. Lower social status and earning potential were also stated as deciding factors in choosing a career in pathology. Pathology residents cited stress-free lifestyle as a motivating factor in choosing pathology as a career. Conclusions: A career in pathology can be rewarding and intellectually stimulating. The fact that a pathologist plays an important role in diagnosis and also patient management must be emphasized in the undergraduate medical curriculum. The medical student will then be able to take an informed decision about his or her career.

Nodal Follicular Lymphomas: A Clinicopathological Study from a Tertiary Care Centre in South India.

The aim of this study was to assess the distribution of nodal follicular lymphomas (FL) among various subtypes of non- Hodgkin lymphoma and to study their clinico-pathological features. Clinical details, histomorphology including grading & patterns and immunoprofile of 44 cases were studied. Majority of the cases were grade 1 (61 %) FL. BCL2 positivity was higher in low grade FLs (97 %). An associated diffuse large B cell lymphoma component was seen in 18 % and was present only in conjunction with grade 3 FL. Majority of our patients (76 %) had a high FLIPI score and belonged to the high risk group. Our study showed that the incidence of FLs is much lower in the Indian population (14.5 %) when compared to western studies and majority were of low grade. Although there was complete initial response to treatment, relapse was common and was much higher in low grade FLs with diffuse areas on histology, Ann Arbor stage III/IV and FLIPI scores of 3-5.

Type 1 Gastric Carcinoid in the Indian Population and Its Association with Multifocal Gastric Atrophy.

AIM: Recent studies have shown an increase in the incidence of gastric neuroendocrine tumors (NETs) (carcinoids). This may be attributable to the frequent employment of endoscopy in clinical practice and the increasing use of proton pump inhibitors. From the literature that is available, it is interesting to note that the profile of patients with gastric carcinoids is different in the Asian population when compared to the western societies. As limited data is available from India, we evaluated retrospectively the clinical profile and pathology of gastric carcinoids presenting to our hospital. MATERIALS AND METHODS: A total of 31 patients with gastric carcinoids who presented to our institution from 2006 till 2013 were included in this study. The clinical data were obtained from the case files and the histopathology slides were reviewed. RESULTS: Gastric carcinoids constituted about 32% of all gastrointestinal (GI) NETs and were second only to duodenal carcinoids in frequency. Men were more commonly affected (74%) and the majority were of type 1 (90%). Multifocal gastric atrophy with intestinal metaplasia was additional features seen in the majority of cases with type 1 carcinoids. CONCLUSION: This study, one of the largest series reported from India, shows that the frequency and profile of gastric carcinoids is different in this population when compared to the west. It also raises the possibility that Helicobacter pylori induced multifocal gastric atrophy might be a triggering factor for the most common type 1 gastric carcinoid rather than autoimmune gastritis. CLINICAL SIGNIFICANCE: Eradication of H.pylori may be a potential preventive strategy for the occurrence of gastric carcinoids. HOW TO CITE THIS ARTICLE: Ananthamurthy A, Correa M, Patil M. Type 1 Gastric Carcinoid in the Indian Population and Its Association with Multifocal Gastric Atrophy. Euroasian J Hepato-Gastroenterol 2016;6(2):106-110.

Cyclin D1 expression in ductal carcinoma of the breast and its correlation with other prognostic parameters.

PURPOSE: Cyclin D1 is a cell cycle regulatory gene emerging as a potentially significant oncogene in invasive breast cancers. In this study, we attempted to see the expression of Cyclin D1 in invasive ductal carcinomas of the breast in our population and correlate its expression with other known prognostic parameters. MATERIALS AND METHODS: A total of 39 cases were selected from our case files from January 2011. Immunohistochemistry for Cyclin D1 was performed and interpreted as positive when >10% of the tumor cells expressed the marker with a moderate to strong intensity of staining. Clinicopathological parameters such as laterality, focality, tumor size, grade, ductal carcinoma in situ (DCIS), axillary lymph node (ALN) metastasis, hormone receptor status and human epidermal growth factor receptor 2 status were analyzed and correlated with Cyclin D1 expression. RESULTS: The patients' age ranged from 30 to 76 years (mean = 53.18). The tumors were unilateral and unifocal in 38 cases; one patient had bilateral synchronous tumors. The majority were grade2 (67.5%) and tumor size T2 (57.5%). Nearly 35% were associated with DCIS and 57.5% had ALN metastasis. Estrogen receptors (ER) and progesterone receptor (PgR) positivity was seen in 65% of the cases and 25% was triple negative. Cyclin D1 expression was seen in 67.5% of the cases in our study. Among the ER, PgR positive and Her-2 negative tumors, Cyclin D1 expression was seen in the majority of cases (92%) cases, whereas none of the triple negative tumors showed Cyclin D1 expression. The other prognostic parameters such as tumor size, grade and lymph node status did not show any association with Cyclin D 1 positivity. CONCLUSIONS: Cyclin D1 expression was seen in 67.5% of ductal carcinoma and it showed a significant correlation with ER, PgR expression (92% in this study), which is in concordance with other similar studies in literature.

Kikuchi-fujimoto disease: a study of 24 cases.

Kikuchi-Fujimoto disease (KFD) is a rare benign disorder predominantly affecting young adults and has a site predilection for cervical lymph nodes. The objective of this study is to analyze the clinicopathological features of KFD. A retrospective study of 24 cases of KFD presenting at a tertiary care hospital in southern India over a 4 year period is presented here. Clinical findings, histopathological findings and follow up data were reviewed. Of the 24 cases encountered, 17 were females and 7 were males. Painless cervical lymphadenopathy was the most common presenting feature. All cases showed typical morphology of KFD with necrosis, karyorrhectic debris and presence of the typical cell types namely crescentic histiocytes and plasmacytoid monocytes. Of the 19 cases with follow up, all resolved within 1 month. The pathologist should be aware of the typical presentation and morphology of KFD in order to distinguish it from the more common causes of cervical lymphadenopathy like tuberculosis (especially in countries like India) as well lymphomas.

Atypical extragonadal germ cell tumors.

AIM: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT) with a subset analysis of those with atypical features. MATERIALS AND METHODS: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. RESULTS: Fifteen children aged 7 days to 15 years (median, 1.5 years) were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor) and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1), anterior neck-thyroid gland (1), mediastinum (4), abdominothoracic extending through the esophageal hiatus (1), retroperitoneal (4) and sacrococcygeal (4). On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years), 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. CONCLUSIONS: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

Papillary thyroid carcinoma with nodular fasciitis-like stroma: a case report.

Papillary thyroid carcinoma (PTC) is the most frequently occurring malignant neoplasm of the thyroid gland and is known to have several morphologic variants. PTC with nodular fasciitis-like stroma (PTC-NFS) is one of the unusual variants of PTC, with only a few cases being reported in the literature. This neoplasm is characterized by extensive reactive stromal proliferation, which may occupy 60 to 80% of the tumor along with areas of a typical papillary carcinoma. We report a case of PTC-NFS and address the diagnostic difficulties posed by the condition's extensive reactive stromal proliferation. We also emphasize that when one encounters a fibroproliferative lesion of the thyroid, a diligent search should also be made for PTC to avoid diagnostic errors.

Orbital inflammation with IgG4-positive plasma cells: manifestation of IgG4 systemic disease.

OBJECTIVE: To describe clinical, radiographic, and morphologic findings in patients with IgG4-positive cells present on orbital biopsy specimens. DESIGN: Retrospective review (from January 1, 1993, through December 31, 2006) of patients with orbital biopsy specimens that excluded lymphoma; comparison of patients with and without IgG4-positive cells on immunostaining. RESULTS: Of 21 patients, 11 had increased IgG4-positive cells (defined as >10 cells on biopsy). Symptoms included eyelid or periocular swelling (8 patients) or proptosis (3 patients), with bilateral involvement in 6 patients. Computed tomographic imaging displayed lacrimal gland mass in 10 patients; 6 patients had lesions in other organs. Two patients had increased serum IgG4 levels. In 10 patients without IgG4-positive cells (≤10 cells on biopsy), 6 had proptosis, 1 had eyelid swelling, 2 had eyelid mass, and 1 had diplopia, all unilateral. None had systemic symptoms. Patients with IgG4-positive cells had longer symptom duration, and their biopsy specimens showed more background fibrosis, lymphoid hyperplasia, plasma cells, and eosinophils. CONCLUSIONS: The clinical appearance, high incidence of bilateral disease, association with lesions in other organs, and increased IgG4 serum levels in some patients-with an increased number of IgG4-positive cells in the biopsy specimen, which shows more background fibrosis, lymphoid hyperplasia, plasma cells, and eosinophils-indicate that these patients have an orbital manifestation of IgG4-associated systemic disease.

Primary synovial sarcoma of the mediastinum : a case report.

Synovial sarcomas commonly occur in the extremities of young adults. A primary occurrence in the mediastinum is very rare with only a few reported cases in the world literature. This paper is about a 42-year-old male who presented with chest pain and dyspnoea on exertion. Imaging showed an anterior mediastinal mass with adhesions to the lung. Pathological examination of the resected mass showed a biphasic neoplasm with a spindle cell component admixed with gland-like elements. The tumour showed positive staining with cytokeratin, epithelial membrane antigen, and Bcl-2 confirming the diagnosis of a biphasic synovial sarcoma. A wide range of neoplasms, both primary and metastatic, occur in the mediastinum, which pose considerable diagnostic difficulties. A synovial sarcoma should always be considered in the differential diagnosis, and immunohistochemistry is an important adjuvant tool in this situation. This paper highlights the importance of recognizing an unusual presentation of this aggressive neoplasm to aid appropriate clinical management.

An unusual case of primary osteosarcoma of the rib in an adult.

Primary osteosarcomas are one of the most common malignant bone tumors principally affecting the long bones in children and adolescents. An unusual case of a primary osteoblastic osteosarcoma of the rib in a 42-year-old male is presented here. The patient underwent a wide excision of the tumor and chest wall reconstruction. Although clinically unsuspected in this unusual site, the classic microscopic feature of a ramifying osteoid matrix amidst the tumor cells was diagnostic of an osteosarcoma.

Fulminant amebic colitis: a study of six cases.

BACKGROUND: Amebic colitis although common, rarely presents as fulminant colitis which has a high morbidity and mortality unless treated promptly and appropriately. AIM: To study the clinical, morphological features and outcome of fulminant amebic colitis (FAC). MATERIALS AND METHODS: A retrospective study of six patients who underwent surgical resections from 2002-06 and were diagnosed with FAC, was carried out. The morphological features assessed included the average number of trophozoites per high-power field and the depth of invasion of trophozoites into the muscularis propria. RESULTS: The study included five adults and one child who underwent surgery for fulminant colitis. Interestingly, a definite preoperative diagnosis of amebic colitis was made only in one patient and suspected in another. Intraoperatively, multiple perforations of the intestine with peritonitis were the most common findings. Gross examination typically revealed multiple ulcers with exudate and intervening normal mucosa. Microscopically, ulceration and myonecrosis with trophozoites within the exudate were seen in all cases. Trophozoites invading the muscularis propria were seen in five cases. Of the cases that showed myoinvasion by trophozoites, two patients expired within two weeks of surgery. One of the patients who expired also showed co-infection with Actinomyces. CONCLUSION: FAC is an uncommon outcome in amebic colitis with a high mortality requiring prompt surgical intervention.