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Context: Non-granulomatous necrotizing lymphadenopathy (NGNL) is not a specific entity. It is seen in various conditions like Kikuchi-Fujimoto disease (KFD), Systemic Lupus Erythematosus (SLE), tuberculosis, lymphoma/metastasis and lymph node infarction. These conditions mimic each other histologically but it is necessary to identify the correct pathology as the treatment differs significantly. Aim of the study: To highlight the subtle morphological features which lead to the etiological diagnosis in NGNL. Materials and Methods: The lymphnode biopsies (N=198), reported in our institute as NGNL, over 4½ year study period, were retrieved. Of these, the benign cases were 64 in total, with 40 cases of KFD and 8 cases of SLE. H&E, special stains and immunohistochemistry slides were reviewed by two pathologists. Histomorphological features like amount of necrosis, apoptotic debris, vasculitis, presence of neutrophils, eosinophils, histiocytes, plasma cells, hematoxylin bodies, Azzopardi phenomenon and thrombus formation were studied. Statistics: Logistic regression analysis was performed to identify the most significant histopathological parameter with each disease. Kendall’s Tau matrix plot analysis was used to measure the correlation between the disease and the histopathologic variables. Results: Features like vasculitis, hematoxylin bodies and Azzopardi phenomenon showed strong correlation with SLE and inverse correlation with KFD. Apoptotic debris, paucity of neutrophils and eosinophils had a strong positive association with KFD. Conclusion: The histological features help in differentiating the various entities associated with NGNL. It is necessary to correlate with clinical details and various laboratory parameters to reach a conclusive diagnosis because these conditions have varied treatment modalities. Keywords: Kikuchi­Fujimoto disease, necrosis, paucity of neutrophils, SLE

Epithelioid hemangioendothelioma (EH) is a rare malignant vascular tumor occurring mainly in the liver and lungs, with bones being a rare site and primarily seen in the adult population. We present a rare case of multicentric EH in the right humerus in an adolescent male, who presented with complaints of pain and swelling in the right shoulder. Radiographs and Computed tomography showed a large expansile lytic lesion in the proximal end of the right humerus with areas of cortical destruction and matrix calcification. On Magnetic resonance imaging, the lesion was predominantly isointense on T1-weighted image, hyperintense on T2-weighted, and Short Tau Inversion Recovery images with prominent flow voids within. On post-contrast sequences, the lesion showed intense heterogenous enhancement with a non-enhancing central necrotic area. Multiple smaller lytic lesions with similar imaging characteristics were also found in the mid and distal shaft of the right humerus and the right coracoid process. Differentials of Telangiectatic osteosarcoma, Giant cell tumor, brown tumors of hyperparathyroidism, and metastasis were considered. Core biopsy revealed that the lesion was an EH. Though the imaging features of EH are non-specific, it may be considered in the differential diagnosis of an expansile lytic bone lesion with no periosteal reaction, showing cortical break and soft tissue component, especially if it is multifocal and multicentric.

Introduction Giant cell tumors of bone (GCTBs) are treated with surgery with or without local adjuvants. Denosumab is a human monoclonal antibody that has recently emerged to be effective in treating unresectable and recurrent GCTBs. Objective In this study, we analyzed the histomorphological changes in GCTB following treatment with denosumab. The expression of histone mutation H3.3G34W by immunohistochemistry (IHC) using mutant specific antibody was also determined. Materials and Methods Of the total 109 GCTBs encountered during the study period, 14 cases with neoadjuvant denosumab therapy were analyzed retrospectively. The post-treatment changes on histopathology were examined on routine hematoxylin and eosin-stained sections. IHC was done using antihistone H3.3G34 antibodies. Statistical analysis was limited to descriptive statistics. No hypothesis testing was performed. Results All these cases except three showed fibrosis with areas of hyalinization, prominent newly formed woven bone along with spindle cells in short fascicles and storiform pattern. There was complete absence and marked reduction in osteoclast-like giant cells in six and five patients, respectively. Only three patients showed a substantial amount of residual osteoclast-like giant cells. IHC with antihistone H3.3G34W antibody showed unequivocal nuclear positivity in the mononuclear cells in nine cases. The mononuclear cells rimming and entrapped within the woven bone were also positive on IHC. The spindle cells in the benign fibrous histiocytoma-like areas and septa of aneurysmal bone cyst-like areas also retained nuclear staining. Conclusion Awareness of post-denosumab-related histopathological changes are necessary to avoid misdiagnosis as fibroosseous lesion and low-grade central osteosarcoma. Expression of mutant-specific H3.3 G34W antibody suggests that the neoplastic stromal cells are largely retained after denosumab therapy. The positive staining of cells both within and those rimming the newly formed woven bone point toward osteoblastic phenotype of the neoplastic stromal cells.

Introduction: Pulmonary neuroendocrine tumors (NETs) comprise a spectrum of tumors ranging from indolent to highly aggressive neoplasm. This study aims to study the clinicopathological and immunohistochemical features of NETs and assess the sensitivity of various IHC markers. Materials and Methods: All consecutive cases of pulmonary NETs diagnosed from January 2016 to June 2019 were analyzed retrospectively. The routine hematoxylin- and eosin-stained sections along with immunohistochemistry (IHC) slides were reviewed. IHC was done using a panel of markers which included synaptophysin, chromogranin, CD56, thyroid transcription factor-1 (TTF-1), p-40, napsin-A, and ki67. Results: Of total number of 53 patients, diagnosis was made on biopsy in 40 patients and resection specimen in 13 patients. Small cell lung carcinoma was the most common (31 cases), followed by 16 cases of typical carcinoid, 5 cases of atypical carcinoid, and 1 case of combined SCLC. Both synaptophysin and chromogranin were positive in all the cases of typical carcinoid. Synaptophysin had better sensitivity than chromogranin in atypical carcinoid and small cell carcinoma. CD56 was positive in 8 out of 9 cases done. TTF-1 was negative in all the cases of typical carcinoid. The sensitivity of TTF-1 in small cell carcinoma was 85.19%. The mean Ki67 labeling index was 1.4%, 6.6%, and 65.6% in typical, atypical carcinoid, and small cell carcinomas, respectively. Conclusion: Synaptophysin was more sensitive than chromogranin, especially in atypical carcinoid and small cell carcinoma. TTF-1 along with high Ki67 differentiates small cell carcinoma from carcinoid.

Context: Percutaneous needle biopsy of lung (PCNBL) is advantageous over bronchoscopic biopsies to obtain adequate sample for peripheral lung lesions. Objective: The objective was to evaluate the diagnostic yield of image-guided PCNBL in the diagnosis of lung lesions and to classify lung carcinomas as per the recently proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society/European Respiratory Society classification for small biopsies modified and adopted by the World Health Organization, 2015. Materials and Methods: A total of 280 image-guided PCNBL were analyzed. The radiological findings and routine hematoxylin and eosin (H&E)-stained sections along with immunohistochemistry (IHC) were analyzed in all the cases. Molecular testing was done depending on tissue diagnosis and availability. Results: Majority (81%) were diagnosed as malignant lesions, with adenocarcinoma (ADC) being the most common. More than 70% were diagnosed on H&E morphology alone, with thirty cases requiring IHC to categorize as ADC. Nearly 60% were categorized as squamous cell carcinoma on morphology alone and the rest required IHC. Though TTF1 showed higher sensitivity than napsin A, the latter is more specific. Both p63 and p40 were found to be highly sensitive for squamous cell carcinoma, but p40 was more specific than p63. Epidermal growth factor receptor could be evaluated on 94.4% of ADC samples, indicating good yield for molecular testing. Conclusion: PCNBL yields adequate sampling for tissue diagnosis and ancillary testing with minimal complications. The use of IHC markers reduces the number of non-small-cell not otherwise specified cases significantly.

Introduction: Unilateral nasal mass can be benign or malignant. Very rarely we will find benign salivary gland tumor in nasal cavity. Pleomorphic adenoma is still the most common pathological variety either in major or minor salivary gland tumors. In the nasal cavity, even though most of the accessory salivary glands are present in the lateral wall of nose, nasal septum remains the most common site of origin. Case Report: A 40-year-old female presented with right-sided nasal obstruction and epistaxis. CT scan of Nose and Paranasal sinuses found a lesion involving the anterior third of the right nasal cavity. The patient underwent complete surgical resection of the tumor via an endonasal approach. Histological examination found a mixed cellular component (epithelial and myoepithelial) and mesenchymatous tissue with chondromyxoid stroma, enabling diagnosis of a typical pleomorphic adenoma. Conclusion: Pleomorphic adenoma is the most common salivary gland tumor but rare to find in the nasal cavity with only few cases reported in the literature. Although benign, the risk of local recurrence, malignant transformation and metastasis requires close long-term follow-up.

Background: The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. Methods: Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. Results: A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. Conclusion: Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.

Background: Bone marrow examination is an essential diagnostic tool in acute leukemia for the determination of lineage of blasts by flow cytometry or immunophenotyping. In cases of dry tap or where facilities of flow cytometry is not available, immunohistochemistry (IHC) on trephine biopsy sections can be used as a supportive tool to diagnose and classify acute leukemia. Materials and Methods: The giemsa-stained peripheral smears and bone marrow aspirate/imprints smears were retrospectively evaluated. IHC was done on trephine biopsy sections using a panel of antibodies which included CD34, MPO, CD117, Tdt, CD3, CD20, PAX5, and CD10 Results: Of the 29 cases diagnosed by IHC on trephine sections, 25 cases could be accurately classified based on the expression of myeloid and lymphoid markers. Majority of the acute lymphoblastic leukemia (ALL) were of B-cell lineage (81.25%), and almost half of the B-ALL were common acute lymphoblastic leukemia-associated antigen positive. Conclusion: IHC on trephine biopsy facilitates the confirmation and subtyping of leukemia in more than 85% cases. A limited panel of antibodies using CD34, MPO, TdT, CD3 CD20, PAX 5, and CD10 can be used for subtyping of leukemias in trephine biopsy sections, especially in centers with limited resources. It obviates the need for a repeat bone marrow procedure where material is not available for flow cytometry.

Background: Ovarian carcinoma represents 30% of all cancers of the female genital tract, of which high-grade serous carcinomas (HGSCs) are predominant, accounting for 70%. Aims and Objectives: To study the clinicopathological findings and to analyze the postchemotherapy changes in tumors treated with neoadjuvant chemotherapy (NACT). Materials and Methods: All cases diagnosed as ovarian serous carcinoma between 2015 and 2017 at our institute were retrospectively reviewed. Clinical and gross findings were collected, microscopic findings were reviewed, and tumor grade was reassessed as per the World Health Organization 2014 criteria. Chemotherapy response score (CRS) was assessed in cases which received prior chemotherapy. Results: Among malignant ovarian tumors, serous carcinoma was the most common, accounting to 38 cases (44.7%). Of these, six were low-grade serous carcinoma and 32 were HGSC. Among HGSC, six (18.75%) cases showed serous tubal intraepithelial carcinoma. Among 18 (47.4%) cases with prior NACT, CRS-1 was seen in six cases, CRS-2 in seven cases, and CRS-3 in five cases. Cancer antigen (CA)-125 levels were markedly raised in all cases. In six cases postchemotherapy, CA-125 levels were below normal with a CRS-2–3. Omental deposits were seen in 15 (39.47%) cases and showed lesser response to prior NACT compared to tumor in the ovary. Conclusion: HGSC is the most common ovarian serous carcinoma. There is correlation between the biochemical and morphological response to chemotherapy in our study. Pathologists should be well aware of postchemotherapy morphological changes in ovarian serous carcinoma.

In this era of targeted therapy, it is important to distinguish the various subtypes of nonsmall cell lung carcinoma (NSCC). Diagnosis based on morphology alone is challenging in poorly differentiated carcinomas and core biopsies. Immunohistochemistry (IHC) helps in specifying the lineage for the subtype of NSCC. Till date, p63 is the most frequently used and sensitive marker for squamous cell carcinoma (SQCC). However, it is not specific and stains a subset of adenocarcinoma (ADC). Thus, a more reliable and specific marker is required for the diagnosis of SQCC.The objective of the study was to validate the diagnostic utility of p40 over p63 in differentiating pulmonary SQCC from ADC and NSCC-not otherwise specified (NOS).A total of 123 cases of NSCC were initially reviewed and subtyped blinded to the results of IHC. This was followed by a review of IHC slides which included p63, p40, thyroid transcription factor 1, Napsin-A, cytokeratin (CK) 5/6, and CK7.There were 64 ADC, 19 SQCC, and 40 NSCC-NOS. IHC helped to confirm the morphological diagnosis in 62/64 ADCs and19/19 SQCCs. IHC classified the cases of NSCC-NOS into NSCC favoring ADC – 12 cases, NSCC favoring SQCC – 10 cases, and NSCC favoring AD-SQCC – 4 cases. Both p63 and p40 showed near equal sensitivity for SQCC (100% and 97%, respectively), whereas p63 showed far lower specificity when compared to p40 (51.3% vs. 100%).The present study confirms and validates that p40 is equally sensitive but highly specific than p63 in detecting SQCC. Hence, we recommend the routine use of p40 instead of p63 for the definite categorization of NSCC of the lung.

Background: The pathophysiology of bone marrow necrosis (BMN) remains unclear; however, the occlusion of microcirculation, accompanied by hypoxemia, causes damage to the cells and plays an important role in development of BMN. Methods: This is a descriptive study; a retrospective review of all trephine biopsies done over period of 22 months January 2017 to October 2018 in Department of pathology showing BMN were included. Only cases identified which showed extensive myelonecrosis > 20% of the diameter of trephine biopsy specimen was included in the study and BMN had to be diagnosed during life were included. Thirty cases met these criteria over this period. Result: In the study period, BMN was diagnosed in 30 samples among 3000 trephine biopsies showed extensive necrosis accounting for 1.0%. Almost all patients on peripheral blood examination shows anemia (100%), around 50% patients present with pancytopenia, followed by anemia with thrombocytopenia. From bone marrow aspiration and trephine biopsy examination shows 30 cases MN,among them 16 patients were acute leukemia either newly diagnosed or post chemotherapy follow-up cases, 10 out of 12 patients had severe bone pain before intuition of chemotherapy, acute leukemia followed by necrotizing granulomatous inflammation metastatic carcinoma were other causes for MN and one case was sickle cell hemolytic anemia. Conclusion: BMN is associated with many diseases, and yet presents with no clear patho physiology. In addition, clinical and laboratory characteristics are non-specific and, in many cases, symptoms are related to the causal condition that is most commonly a hematological disease.

BACKGROUND: Thymomas are not so common tumors that are encountered in day-to-day pathology reporting. The WHO system was proposed in 2015. Although, through its detailed reporting, the WHO elaborates all subtypes and morphological clinches to diagnosis, it was important to ascertain its reproducibility in our day-to-day reporting. AIMS: The aims of the study were (1) to study the interobserver agreement, concordance rates, and variability in the classification of a large number of thymomas received in our department as per the WHO 2015, (2) to correlate the WHO subtype with Masaoka–Koga stage, and (3) to study the variations in demography of thymomas in Indian patients as compared to those reported in the literature. SETTING AND DESIGN: This retrospective study was done at a tertiary care teaching hospital with huge surgical oncology patient load, also pertaining to the cardiothoracic surgeries. It is predominantly an interobserver agreement design to study the reproducibility of the WHO 2015 classification on thymic epithelial tumors. METHODS: Four pathologists have independently reviewed histopathology slides of 65 cases of thymomas and classified them into predefined categories. Kappa statistics was applied to the observations. RESULTS: There was a substantial interobserver agreement in overall classification of thymomas with a Cohen's kappa score of 0.66. A better score was achieved for the classification of Group B thymomas. The WHO subtypes correlate well with the Masaoka–Koga staging system, and this finding is statistically significant. This article also presents the clinical details of a large number of thymoma cases. CONCLUSION: The new WHO classification has good reproducibility among pathologists in thymoma reporting.

Introduction: Leukemia is the most common childhood malignancy accounting for 30%–40% of cases. Acute lymphoblastic leukemia is the most common leukemia in children with peak incidence in 2–6 years of age. The present study aims to assess the incidence of acute leukemia in patients presenting with musculoskeletal manifestations. Materials and Methods: This is a retrospective study conducted in a tertiary center from January 2014 to December 2018. A total of 63 children presented with musculoskeletal manifestations and underwent bone marrow examination. Based on final marrow diagnosis, the study group was divided into leukemic and nonleukemic groups. Results: Fever was the most common presenting complaint and was present in all the patients of both the groups. The occurrence of hepatosplenomegaly was comparatively higher in the leukemic group than in patients with juvenile idiopathic arthritis (JIA). The predominant type of arthritis was oligoarticular (68.15%) in the leukemic group and polyarticular (77.27%) in the nonleukemic group. Rheumatoid rash was noted in 20% of JIA patients, and none of the patients in the leukemic group had rash. The percentages of anemia, leukopenia, and thrombocytopenia were statistically higher in leukemia patients than in JIA patients. Conclusion: Bone marrow studies are a prerequisite in diagnosing leukemias. However, based on the presence of few atypical clinical and laboratory features, leukemia can be excluded in JIA patients.

Objective: To assess P63 expression in giant cell-containing lesions of the bone (GCLB) and to determine its utility in differentiating giant cell tumor of the bone (GCTB) from other GCLBs. Material and Method: Cases diagnosed as GCLB on histopathology were included in the study. P63 immunohistochemistry was performed in all the cases. The percentage of cells showing nuclear positivity was assessed in the non-giant cell component. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the total 53 cases studied, the majority were GCTBs (23), followed by 12 cases of chondroblastomas (CBL) and 18 other giant cell lesions (GCLs). All giant cell-containing lesions except one case of CBL and brown tumor of hyperparathyroidism (BTH) showed P63 staining in the non-giant cell component. However, the mean P63 labeling of GCT (52.6%) was higher compared to CBL (28.3%), aneurysmal bone cyst (ABC) (15.2%), non-ossifying fibroma (NOF) (24.5%), giant cell lesion of small bones (GCLSB) (11%), BTH (6.8%) and chondromyxoid fibroma (CMF) (12.3%), with a p-value of 50% is applied.

Background: Non chronic myelogenous leukemia (non-CML)/BCR-ABL-negative myeloproliferative neoplasms (MPNs) include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) (apart from chronic neutrophilic leukemia and chronic eosinophilic leukemia, which are rare). They are uncommon clonal disorders of adults, with an incidence ranging from 0.5 to 3/100,000 persons, BCR-ABL negative, and characterized by the activation of Janus-associated kinase 2 (JAK2). Very few studies have been reported from India. Aims and Objectives: The aims and objectives of this study were to analyze the clinicopathological spectrum and to determine the frequency of JAK2 mutation in patients of non-CML/BCR-ABL negative MPNs. Materials and Methods: Clinical and morphological features and frequency of JAK2 mutation in patients with PV, ET, and PMF were studied at a tertiary care hospital. The material was retrieved from the hematopathology records and reviewed. Results: JAK2V617F mutation was found in 10 of 14 cases (71%) of MPNs, 100% in PV, 50% in ET, and 71% of idiopathic myelofibrosis. The presence of JAK2V617F mutation was associated with a higher hemoglobin level (P < 0.05), a higher TLC (P < 0.05), and higher age (P < 0.05). Results showed that there are morphologic differences, and megakaryocytic morphology represents a useful clue for the differential diagnosis of these three BCR-ABL-negative MPN subtypes. Conclusion: The JAK2 V617F mutation was detected in 71% of patients with MPN disorders. Peripheral blood mutation screening for JAK2 V617F should be incorporated into the initial evaluation of patients suspected to have MPNs. Differences in megakaryocytic morphology provide the histomorphological hallmark of BCR-ABL-negative MPN subtypes.

Soft tissue tumors, including sarcomas are complex and diagnostically challenging tumors. This is as a result of their heterogeneity and overlapping clinicopathological, immunohistochemical and also molecular features, the latter to some extent. More than 80 types of sarcoma have been described. Current management, which is best offered at centers with active multidisciplinary care, is based on balancing oncologic and functional outcomes in such cases. This has transcended into the types of specimens received for grossing these rather uncommon tumors. Over the years, diagnostic specimens have reduced in their sizes from, open biopsies to core needle biopsies. These specimens need to be adequately and judiciously triaged for ancillary techniques, such as molecular testing. Conservative surgeries have led to resected specimens for marginal assessment. Lately, post neoadjuvant (chemotherapy or radiation therapy)-treated resection specimens of soft tissue sarcomas are being submitted for surgical pathology reporting. This article focuses on the grossing of soft tissue tumors, including sarcomas, in terms of types of specimens, grossing techniques including rationale, tissue triage, reporting, and recommendations from the surgical pathologists actively engaged in reporting musculoskeletal tumors, based on current evidence.

Primary bone tumors, including sarcomas, are rare tumors and require a multidisciplinary approach, including inputs from a radiologist, pathologist, medical oncologist, and surgical and radiation oncologist, for optimal management. Over the years, there has been a paradigm shift toward the treatment of bone sarcomas, from radical resections to conservative surgical procedures, to achieve improved clinical and functional outcomes. This has led to receiving and processing various types of specimens in orthopedic oncopathology. Grossing and reporting of bone tumors require expertise. This review focuses upon the types of biopsies, grossing techniques of various specimens in orthopedic oncology and reporting, with rationale and recommendations from pathologists, actively involved in reporting and pursuing a special interest in bone tumors, based on current evidence. Furthermore, there is a section on some of the updates in the diagnosis of bone tumors, based on the recent fifth edition of the World Health Organization classification of tumors of soft tissues and bone.

Objective Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinico-patho-radiological diagnosis which rarely presents as a pulmonary manifestation of lupus. In this concise report, organizing pneumonia was found as the sole pulmonary manifestation of SLE in different age groups. Method All three patients diagnosed with SLE according to SLICC 2012 classification criteria, were admitted in rheumatology ward of NIMS hospital, Hyderabad, India from May to November, 2018. Their diagnosis of BOOP was either biopsy proven or imaging guided. Review of literature was done with MeSH terms (SLE, BOOP) in PubMed and approximately 10 articles were reviewed including latest of 2019 published in Scientific Reports. Result There were three patients – one juvenile lupus and two adults. Two patients were male and one female. All three patients had SLE with high disease activity. They all had organising pneumonia as pulmonary manifestation with other organ involvement. Juvenile patient had a fatal outcome while the others had a good recovery with steroid and immunosuppressive. Conclusion BOOP is a rare pulmonary manifestation in lupus. It can be diagnosed early with more precision using computerised tomography of lung without waiting for biopsy report. This will result in a better prognosis by rapid initiation of corticosteroid and immunosuppressive treatment.

Ectopic hamartomatous thymoma is a rare neoplasm with classic anatomical location and characteristic histological and immunohistochemical features. Awareness of ectopic hamartomatous thymoma is essential to accurately diagnose these lesions which clinically mimics lipoma. Based on the morphologic and immunophenotypic features, the authors stress the need to discontinue the existing term of ectopic hamartomatous thymoma and replacing it with suitable nomenclature that aptly denotes its phenotype and possible histogenesis. The authors propose a new terminology “Triphasic Epithelial Myoepithelial Mesenchymal Branchial Anlage Tumor” as it encompasses three important constituents of the lesion (epithelial, myoepithelial, and mesenchymal) and its possible histogenesis in relation to branchial remnants.

Lung cancers commonly occur in the sixth to eighth decades of life. They are extremely uncommon in first two decades of life. We describe the clinical, radiological, and pathological findings in a 19-year-old female diagnosed with an invasive mucinous adenocarcinoma that was initially mistaken and treated as tuberculosis. This case is being presented to emphasize inclusion of this entity in the differential diagnosis of multifocal consolidations and nodules that do not resolve or persist after treatment, and also to create awareness of the occurrence of lung cancers in young patients.

The manifestations of tuberculosis (TB) are myriad and can affect any organ. Involvement of breast by TB is rare and the condition is often mistaken with breast cancer or pyogenic breast abscess. We report the case of a 75-year-old woman with long standing type 2 diabetes mellitus who presented with a swelling in the left breast. Core biopsy of the swelling showed necrotizing epithelioid granulomas with acid-fast bacilli. The patient responded well to short-course anti-TB treatment. The present case documents the uncommon isolated occurrence of TB of the breast in a patient with long standing type 2 diabetes mellitus.

Objectives: The objective of this study is to evaluate the diagnostic yield of endobronchial biopsy in various neoplastic and nonneoplastic lung lesions. Patients and Methods: A total number of 204 consecutive cases of fiberoptic bronchoscopic-guided endobronchial biopsies was analyzed. The bronchial wash (BW) samples collected simultaneously during the biopsy were correlated with final histopathology diagnosis. Results: The bronchoscopic findings mainly included endobronchial mass, increased mucosal vascularity, and mucosal irregularities. Of the 184 adequate biopsy samples, 32.3% were neoplastic, 20.5% nonneoplastic, and remaining 41.3% revealed normal histology. The nonneoplastic lesions included mainly nonspecific inflammation, granulomatous inflammation followed by few cases of squamous metaplasia, one case each of tracheobronchopathia osteochondroplastica, mycobacterium spindle cell pseudotumor, and cytomegalovirus infection. Among the malignant tumors, adenocarcinoma (ADC) was the most common followed by squamous cell carcinoma (SQCC) and non-small cell carcinoma-not otherwise specified. On immunohistochemistry, Napsin-A showed better sensitivity than thyroid transcription factor-1 for ADC. P40 was found to be most sensitive and specific markers for SQCC. Neuroendocrine tumors included seven small cell carcinoma and three carcinoids. Both chromogranin and synaptophysin were found to be equally sensitive neuroendocrine markers. The bronchoscopically normal airways mostly revealed normal histology with few showing mild nonspecific inflammation. On the contrary, all except one case of neoplasm had mass lesions on bronchoscopy. Conclusion: EBB provides sufficient tissue for morphological and immunohistochemical characterization of malignant lesions. BW cytology has poor concordance with EBB in the diagnosis of malignancies with nearly 70% cases being false negative.

A 66-year-old man presented with dry cough and shortness of breath on exertion of 6 months' duration. There were no complaints of fever and hemoptysis. His history was significant for recurrent episodes of respiratory tract infections over the previous 4 years. He had also had episodes of recurrent otitis media and pus discharge from the left ear for 3 years, with progressive loss of hearing. There was no history of recurrent skin infections or diarrhea. He was treated symptomatically with antibiotics by local general practitioners. He was a nonsmoker and did not drink alcohol, and there was no history of environmental or occupational exposure. He had been known to have diabetes for 10 years. He had negative results for the presence of HIV and hepatitis B surface antigen.

Introduction: The diagnosis of Hodgkin lymphoma (HL) is defined in terms of its microscopic appearance (histology) and the expression of cell surface markers (immunophenotype). Aims and objectives: This study aims to analyze the clinical features, histomorphology, and immunoprofile of over 200 patients of HL diagnosed over a period of 4 years at our institute and to determine relative frequency of various histological subtypes (based on WHO classification) in relation to age and sex distribution in this part of the country. Materials and Methods: All HL cases diagnosed between January 2006 and December 2009 were retrieved from hospital records. The histopathology of both lymph node and bone marrow biopsy (where ever available) along with immunohistochemistry (CD15, CD30, CD20, and ALK) were reviewed. Results: There was a bimodal age distribution. HL affected people a decade earlier than in the western population. The most common presenting complaint was cervical lymphadenopathy. Mixed cellularity was the most frequent subtype (67%), followed by nodular sclerosing subtype (23.5%). Group A (CD15+, CD30+, CD20−), which represents the archetypical immunophenotype of classical HL (CHL) was the most common type (60.6%). The number of CD15 negative CHL was 35.8% and CD20 positive CHL was 17.5%. CD15 negativity with CD20 positivity was seen in 5% CHL. One out of seven CD20 positive CHL patients showed relapse. Conclusion: In this paper, we have discussed in detail about various clinical and histopathological parameters of HL and their relative frequency in various histological subtypes. This paper is being presented as it is a rather large study from India taking into consideration the clinical, pathologic, and immunophenotypic profile of the patients.

Metachronous multicentric giant cell tumour (GCT) of bone is rare. We report a case of a 21-year-old man with metachronous multicentric GCTs, with five (including one recurrence) documented lesions reported over a span of 9 years involving various sites, which included the fifth metacarpal bone of the right hand, the intermediate cuneiform bone of the right foot, the left proximal humerus and the lateral malleolus of the right tibia. The radiological appearance of these lesions in these various sites with correlation among clinical history, histopathology and the treatment approach is described in this report. He is undergoing regular follow-up and has now once again presented with recurrence of the right tibial lesion. The case is reported for its rarity.

Endobronchial metastasis from extrapulmonary malignant tumors is rare. The clinical and radiological features of endobronchial metastases and primary bronchogenic carcinoma are indistinguishable. Here, we report a case of isolated endobronchial metastasis of renal cell carcinoma almost a decade after initial presentation. The importance of histopathology and immunohistochemistry has been emphasized in this case. It is thereby worthwhile to consider endobronchial metastases as a differential diagnosis in patients with persistent pulmonary symptoms having a previous history of non-pulmonary malignancy.

Identification based on histology alone has limitations as Aspergillus species share morphology with other filamentous fungi. Differentiation of Aspergillus species from hyalohyphomycetes and dematiaceous fungi is important as the antifungal susceptibility varies among different species and genera. Given these problems, ancillary techniques are needed to increase specificity. Our aim was to study the utility of immunohistochemistry (IHC) with anti-Aspergillus antibody in the identification of Aspergillus species and to differentiate them from other filamentous fungi. Fifty formalin fixed, paraffin embedded tissue sections including 47 from cases of culture proven filamentous fungi, 3 from colonies of cultures of hyalohyphomycetes, and 11 smears from cultures were subjected to IHC studies using polyclonal rabbit anti-Aspergillus antibody (Abcam, UK) after antigen retrieval. The IHC on tissue sections was positive in 88% cases involving culture proven Aspergillus species. There was no cross reactivity with Mucorales species, Candida species, dematiaceous fungi and hyalohyphomycetes. Hence immunohistochemistry can be used as an ancillary technique for the diagnosis of Aspergillus species.

Background: The clinicopathological and immunohistochemical data of solid-pseudopapillary neoplasm (SPN) from India are limited. Our objectives were to evaluate various histopathological parameters and immunomarkers to elucidate the best possible immunomarker combination that can accurately diagnose these tumors. Materials and Methods: Clinicopathological features of 33 consecutive cases of SPN were retrospectively analyzed. Immunohistochemistry (IHC) was performed on a tissue microarray of 31 of these cases with antibodies to pan-cytokeratin (CK), vimentin, CD 10, E-cadherin, β-catenin, estrogen receptor (ER), progesterone receptor (PR), chromogranin. Results: Totally, 32 of 33 patients were females with a mean age of 26 years (range 12-62 years). Majority presented with abdominal pain (93.93%) and/or abdominal mass (48.48%). Location in pancreas included tail (14), head (7), body and tail (6), body (5) and neck (1). The mean diameter of the tumor was 8.6 cm (range 0.5-16 cm). Surgical exploration was done in all cases. On IHC, tumor cells were consistently positive for vimentin and negative for chromogranin (100%). CK was positive in 12 cases (38.7%), CD 10 showed perinuclear dot positivity in 14 (45.16%) cases and cytoplasmic positivity in 05 (16.12%) cases. All cases showed loss of membranous staining for both β-catenin and E-cadherin with nuclear positivity in 90.32% and 70.16% cases, respectively. PR was positive in 20 (64.51%) cases, while all of them were negative for ER. Conclusion: Solid-pseudopapillary neoplasm is a tumor commonly affecting young females. Loss of membrane expression of β-catenin and E-cadherin with nuclear positivity can be used confirm the diagnosis of SPN.

Context: Lung cancer is an important cause of cancer-related deaths worldwide. There is an increasing incidence of lung cancer in never smokers and a shift of histology from squamous cell to adenocarcinoma globally in the recent past. Data on treatment outcomes with newer platinum doublets is scant from India. Aims: To study the clinicopathological features, response rates (RRs), progression-free survival (PFS), overall survival (OS), and the 1, 2, and 3 years survival, in patients with advanced nonsmall cell lung cancer (NSCLC). Materials and Methods: Data of all patients who received chemotherapy for Stage IIIB and IV NSCLC between January 2010 and June 2014 were retrospectively analyzed. Statistical Analysis Used: Univariate analysis for OS was done by plotting Kaplan–Meier curves and the log-rank test was used to calculate P values. Logistic regression analysis for OS was carried out using MedCalc statistical software. Results: A total of 353 patients received chemotherapy. Of these, 256 were evaluable for outcome parameters. The median age at presentation was 58 years with a male:female ratio of 2.53:1. The smoker:nonsmoker ratio was 1:1. Adenocarcinomatous histology was the most common both in smokers and nonsmokers reported in 70.8% patients. Epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocation were seen in 35% and 3% of patients, respectively. The RR, median PFS, OS, 1, 2, and 3 years survival were 80%, 8 months, 12.1 months, 51.5%, 12.7%, and 4.2%, respectively. There was no significant survival difference among the treatment regimen used but the response to I line chemotherapy impacted survival. Female gender, performance status, and nonsquamous histology were significant predictors of OS (P = 0.0443, P = 0.0003, P = 0.048, respectively). Conclusions: There was an increase in the incidence of nonsmokers. Adenocarcinoma was the most common histology in both smokers and nonsmokers. Treatment outcomes in advanced lung cancer were better compared to the past with the advent of newer platinum doublets and EGFR tyrosine kinase inhibitors. The response to first-line chemotherapy significantly impacts outcomes in advanced NSCLC.

Background: The gastroenteropancreatic neuroendocrine tumors (GEPNET) have a characteristic histologic appearance unrelated of the exact site of origin. However the behavior of these tumors are different in each of these sites. In this article we study the clinicopathological features of GEPNET. These tumors were classified and graded according to WHO 2010 criteria. The immunohistochemical (IHC) features were evaluated and the grade of the tumor was correlated with Ki67. Methods: A total of 40 cases of GEPNET diagnosed on biopsies as well as resected specimens were analyzed from January 2012 to June 2015. Results: There were 28 resected specimens and 12 biopsies. Majority of the gastric neuroendocrine tumors (NET) showed classic morphology of cells arranged in islands. There were 3 cases each of grade 1 and grade 2 and one was diagnosed as mixed adenoneuroendocrine carcinoma (MANEC). All the duodenal NET were well differentiated (grade 1). There were 8 cases in colon and rectum, of which 4 cases were grade 3 and 3 cases were grade 2. Majority of the pancreatic tumors were grade 1. The mean mitotic count along with ki67 had good correlation in NET of stomach, duodenum colon and rectum. Conclusions: The most common site was small intestine followed by pancreas. Majority of the tumors were NET G1. Tumors from colorectal region were mostly NEC G3. There was a strong correlation by spearman correlation analysis between Ki67 and mitotic count and moderate correlation between ki67 and tumor grade as well as mitotic rate and tumor grade. Ki67 was helpful in grading these tumors.

Lynch syndrome (LS), the most common form of familial CRC predisposition that causes tumor onset at a young age, is characterized by the presence of microsatellite instability (MSI) in tumors due to germline inactivation of mismatch repair (MMR) system. Two MMR genes namely MLH1 and MSH2 account for majority of LS cases while MSH6 and PMS2 may account for a minor proportion. In order to identify MMR genes causing LS in India, we analyzed MSI and determined expression status of the four MMR genes in forty eight suspected LS patient colorectal tumor samples. Though a majority exhibited MSI, only 58% exhibited loss of MMR expression, a significantly low proportion compared to reports from other populations. PCR-DNA sequencing and MLPA-based mutation and exonic deletion/duplication screening respectively, revealed genetic lesions in samples with and without MMR gene expression. Interestingly, tumor samples with and without MMR expression exhibited significant differences with respect to histological (mucin content) and molecular (instability exhibited by mononucleotide microsatellites) features. The study has revealed for the first time a significant proportion of LS tumors not exhibiting loss of MMR expression.

Background: Parachordomas are rare soft tissue tumors commonly occurring in limbs, chest, Abdomen, and back. The World Health Organization (WHO) classification includes parachordomas in the same group as mixed tumors and myoepitheliomas. Exact histogenesis of this tumor is unclear. Case Description: A 52‑year‑old male presented with headache and blurring of vision since one month. Preoperative computed tomography (CT) scan of brain revealed left parieto‑occipital tumor extending up to the trigone. Total excision of the tumor was done. Histopathologically, the tumor was composed of relatively uniform cells with eosinophilic cytoplasm in a myxoid stroma and with cartilaginous and osseous metaplasia. The tumoral cells were immunoreactive for cytokeratin, epithelial membrane antigen (EMA), S‑100, and vimentin. The constellation of findings revealed the tumor to be parachordoma. Magnetic resonance imaging (MRI) brain during follow‑up at one year showed no recurrent tumor. No adjuvant therapy was given to this patient. Conclusion: This is the first reported case of primary intracranial parachordoma. It is difficult to diagnose the lesion preoperatively by imaging alone. Long‑term follow‑up is necessary in view of few reports in literature of recurrence and metastasis, of parachordomas in other anatomical locations.

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.

Hepatosplenic T cell lymphoma is a rare form of extra nodal and systemic neoplasm derived from cytotoxic T cells and represents less than 1 % of all non Hodgkins lymphoma. Here we present a case of hepatosplenic T cell lymphoma in a 30 year old male who presented with icterus, pancytopenia and hepatosplenomegaly, highlighting the diagnostic conundrum and pointers towards an accurate diagnosis. Histologically the sinusoids of liver and splenic red pulp were infiltration by CD 3 positive neoplastic lymphoid cells. The pattern of marrow involvement was very subtle and diagnosis was difficult to establish without the help of immunohistochemistry. This case highlights the importance of considering hepatosplenic T cell lymphoma as differential diagnosis in the clinical setting of pancytopenia with hepatosplenomegaly to allow timely diagnosis of these aggressive neoplasms.

Background: The role played by cytology in primary diagnosis is undeniable. With improved management protocols and targeted therapy, the need for accurate diagnosis has become mandatory. Immunochemistry and molecular techniques are increasingly being used on limited tissue samples. Aims: This study was conducted to find out the impact of immunocytochemistry (ICC) on cytology material in cytology practice. Materials and Methods: Immunochemistry was done on alcohol-fixed smears and cell-block preparations. It was done with i6000 BioGenex autostainer using BioGenex reagents. Results: A total of 148 cases occurring over a period of 3 years (September 2010-June 2013) were analyzed. Staining was done on cytology smears in 77 cases and on cell-block sections in 71 cases. ICC helped in diagnosis in 8 cases, confirmed the diagnosis in 26 cases, helped in subtyping in 60 cases, and helped in prognostication in 6 cases. ICC has altered the diagnosis in two cases. It was noncontributory in 43 cases, and the material was inadequate in three cases. Conclusion: In 102 cases (69%), ICC proved to be a useful adjunct in the diagnosis and prognostication; hence, its use is recommended in practice to aid in cytology services.

Carcinosarcomas of the lung are uncommon neoplasms and are presently categorized along with sarcomatoid carcinomas in the WHO 2004 classification. Morphological recognition of individual components in a surgical specimen is usually straightforward. The respiratory epithelium is also a rare site for salivary gland type tumors. A 72-year-old lady who was investigated for an episode of hemoptysis was found to have a well circumscribed intraluminal tumor. The histo-morphological features were unique and composed of mucoepidermoid carcinoma and undifferentiated sarcoma. To the best of our knowledge, this unusual morphological combination has never been reported in literature.

Context: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. Aim: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. Materials And Methods: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. Results: There were 61 such cases (51 males, 10 females). The age range was 7–78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). Conclusion: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.

Background and Objective: Zygomycosis is an emerging infection worldwide. Pulmonary zygomycosis (PZ) is uncommon with only few reported series from India. Materials and Methods: All cases of PZ diagnosed on histopathology between 1995 and 2008 were included. Clinical and imageological findings were noted in all cases. Routine hematoxylin and eosin-stained sections were studied to assess the pathology; Gomori's methenamine silver (GMS), periodic acid Schiff were done for delineating fungal morphology. Culture reports were collected wherever available. Treatment and outcome details were noted. Results: Seven patients were diagnosed with PZ during the study period, which included six males and one female patient. Six of these had diabetes mellitus (DM) and one patient was on chemotherapy for the treatment of Hodgkin's lymphoma. Fever and cough were the most common presenting features. Consolidation with or without cavitation was seen in six patients and lung abscess with fungal ball in one patient. All six patients with DM had upper lobe involvement and four had multiple lesions. Histological sections revealed necrotizing inflammation, hemorrhagic infarcts and angioinvasion. Culture was available in two patients, which grew Rhizopus oryzae. Five patients succumbed to disease and remaining two were lost to follow-up. Conclusion: Diabetes mellitus is the most common predisposing factor for PZ and carries high mortality.

Skeletal metastasis from a cardiac myxoma is rare. We describe an extremely unusual case of a cardiac myxoma metastasing to the femur in a 46-year-old female presenting with pain in the right hip. Radiographs showed an expansile lytic lesion with pathological fracture involving the neck and proximal shaft of the right femur. Histology revealed features of cardiac myxoma with heterologous glandular elements, which was initially mistaken for a metastatic mucin-secreting adenocarcinoma.

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.

Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. Because there are few reports about these tumors from India, we aimed to study the clinico-pathological and immunohistochemical features of CNS HPC. During 2000 to 2008 all 23 patients diagnosed with HPC of CNS at our Institution were reviewed in the study (11 males and 12 females, mean age of 46 years). Clinical, radiological and histopathological features were reviewed. There were 14 patients with grade II and nine with grade III tumors. Immunohistochemistry with antibodies to epithelial membrane antigen (EMA), vimentin, S-100, CD34 and Ki-67 was done on routinely processed, paraffin-embedded sections of 20 tumors. All patients were EMA and S-100 negative, and vimentin positive. CD34 was positive in only five out of 20 patients. The mean Ki-67 labeling index was 4.25% in grade II tumors and 7.8% in grade III tumors. We concluded that HPC are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior, although they resemble each other clinically and radiologically, HPCs need to be differentiated from meningiomas.

BACKGROUND: Malignant mesotheliomas are histologically heterogeneous neoplasms. Definite diagnosis requires a varied panel of immunohistochemical (IHC) markers to differentiate these from histological mimics. Only a few case series have been reported in the Indian literature where mesotheliomas have been analyzed on routine histology and IHC. AIM: To evaluate the histological features of malignant mesothelioma and to elucidate the best possible immunomarker combination useful in different scenarios. MATERIALS AND METHODS: A total of 24 cases of malignant mesotheliomas of different sites encountered over a 6-year period were retrospectively analyzed with regard to their histomorphology and IHC findings. RESULTS: The pleura was the most common site of involvement (16 cases) followed by peritoneum (5 cases) and pericardium (3 cases). Epithelioid mesothelioma was the most common histological type (15 cases, 62.5%) followed by sarcomatoid (5 cases, 20.84%), deciduoid (2 cases, 8.34%), and 1 case each of desmoplastic and biphasic mesothelioma. Among the mesothelial markers, WT1 was positive in 17 of 20 (85%) cases and calretinin was positive in 20 of 21 (95.23%) cases. D2-40 and CK5/6 were positive in all cases where they were studied. Adenocarcinoma markers TTF-1, napsin A, and CEA had very high negative predictive value in ruling out mesothelioma. CONCLUSION: The differential diagnosis of mesotheliomas varies with histological type and tumor location. Judicious use of various combinations of IHC markers in different situation has been highlighted in this article.

Ewing's sarcoma is the second most common malignancy of bone among children. It commonly affects the diaphysial region of long bones, while small bones of hands and foot are rarely affected. We report a case of calcaneal Ewing's sarcoma which was misdiagnosed as fungal chronic osteomyelitis and treated inappropriately. High index of suspicion is required in diagnosing tumors at rare sites to avoid undue delay in initiating appropriate therapy.