Myeloid sarcoma: Experience from a tertiary care center in southern India - A series of eight unusual cases.

BACKGROUND: Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm. MATERIALS AND METHODS: This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details. RESULTS: These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate. CONCLUSION: Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.

Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults: A Multicenter Study From India.

PURPOSE: Colorectal cancer (CRC) in young adults is a rising concern in developing countries such as India. This study investigates clinicopathologic profiles, treatment patterns, and outcomes of CRC in young adults, focusing on adolescent and young adult (AYA) CRC in a low- and middle-income country (LMIC). METHODS: A retrospective registry study from January 2018 to December 2020 involved 126 young adults (age 40 years and younger) with CRC. Patient demographics, clinical features, tumor characteristics, treatment modalities, and survival outcomes were analyzed after obtaining institutional ethics committees' approval. RESULTS: Among 126 AYA patients, 62.70% had colon cancer and 37.30% had rectal cancer. Most patients (67%) were age 30-39 years, with no significant gender predisposition. Females had higher metastatic burden. Abdominal pain with obstruction features was common. Adenocarcinoma (65%) with signet ring differentiation (26%) suggested aggressive behavior. Limited access to molecular testing hindered mutation identification. Capecitabine-based chemotherapy was favored because of logistical constraints. Adjuvant therapy showed comparable recurrence-free survival in young adults and older patients. For localized colon cancer, the 2-year median progression-free survival was 74%, and for localized rectal cancer, it was 18 months. Palliative therapy resulted in a median overall survival of 33 months (95% CI, 18 to 47). Limited access to targeted agents affected treatment options, with only 27.5% of patients with metastatic disease receiving them. Chemotherapy was generally well tolerated, with hematologic side effect being most common. CONCLUSION: This collaborative study in an LMIC offers crucial insights into CRC in AYA patients in India. Differences in disease characteristics, treatment patterns, and limited access to targeted agents highlight the need for further research and resource allocation to improve outcomes in this population.

Blastoid Variant of Mantle Cell Lymphoma with Extranodal Presentation and Aberrant CD10 Expression.

Mantle cell lymphoma (MCL) constitutes 3%-10% of non-Hodgkin lymphoma and is characterized by t (11:14)(q13;q32). The common presentation is generalized lymphadenopathy with weight loss, infrequently night sweats, and fever. Among histological subtypes of MCL, the blastoid variant of MCL constitutes 10%-15% of all the cases. It is challenging to diagnose the blastoid variant of MCL based on its morphology alone as it mimics large B-cell lymphoma. Hence, the immunophenotyping and molecular studies aid in its correct diagnosis. We report an elderly man diagnosed with blastoid variant MCL. He presented with disseminated soft-tissue and subcutaneous nodules, and showed aberrant CD10 expression. Presentation of the extranodal site and aberrant CD10 expressions carries an overall poor prognosis. CD10-positive MCL can be mistaken for large B-cell lymphoma.

Algorithmic approach utilizing histology and immunohistochemistry for the current classification of diffuse glioma.

INTRODUCTION: Diffuse glioma constitutes 28% of primary brain tumors. Until recently morphologic appearance was the only criterion for classifying these tumors. However, WHO 2016 incorporates molecular information in the primary diagnosis of gliomas such as Isocitrate dehydrogenase 1 (IDH1), Alpha thalassemia/mental retardation syndrome X inked (ATRX) as well as 1p/19q codeletion on FISH. In a resource-limited setup where FISH is not available, Alpha internexin (INA) has been suggested as a surrogate IHC marker. MATERIAL AND METHODS: Cross-sectional study conducted in the Department of Pathology for two years. Tissue blocks and clinical as well as radiological details were obtained from departmental archives. After assessing the morphologic details, routine IHC markers such as GFAP, Ki67 and P53 along with molecular markers like IDH-1, ATRX, and lNA were applied. RESULTS: Out of 55 cases of diffuse glioma, 23 cases of astrocytoma and 32 cases of oligodendroglioma with an overall mean age of presentation of 41.49 ± 12.47 years. IDH-1 expression among diffuse glioma was 89.1% in our study. Alteration in the ATRX gene expression was observed in 95.7% of astrocytomas. 75% of oligodendrogliomas expressed INA with no significant difference in expression between the two grades. Based on the algorithmic approach using molecular surrogate markers, diffuse gliomas were categorized into six distinct groups. IDH-mutant, ATRX loss of expression astrocytoma and IDH-mutant, INA positive oligodendroglioma are two categories that do not require further molecular testing. This comprises 72.7% of the cases and these do not warrant further workup. CONCLUSION: Implementation of combined phenotypic-genotypic diagnosis with the use of histomorphology and immunohistochemical surrogates for molecular genetic alterations will yield more homogeneous and narrowly defined diagnostic entities which will provide better prognostication and definitive treatment. It also is cost-effective in a resource-limited setup.

Concomitant Diagnosis of Plasmablastic Lymphoma and Chronic Lymphocytic Leukemia: A Rare Phenomenon.

Plasmablastic lymphoma (PBL) is a rare, aggressive non-Hodgkin lymphoma which shows blastic morphology and an immunophenotype of plasma cell differentiation while chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma is an indolent B-cell lymphoma and has a variable clinical course. A CLL transforming into a PBL and the coexistence of CLL with PBL are both extremely rare findings. We report an unusual case of a 72-year-old HIV-negative male who presented with a gingival swelling which was diagnosed as PBL with simultaneous CLL in the blood and bone marrow. Further, in this case, the PBL spontaneously regressed postbiopsy adding to the peculiarity and rarity of this case. This could be due to immune system modulation and can open up a new window to the treatment strategies of PBL in the future.

Performance of HScore in Reactive Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life threatening systemic hyperinflammatory disorder that leads to multiple organ damage. The most widely used diagnostic guidelines are the HLH 2004 guidelines proposed by the Histiocyte society. Recently, Fardet et al. has proposed a Scoring system, "HScore" for diagnosis of reactive HLH. To test the performance of "HScore" in diagnosis of reactive HLH and compare the credibility of the same with the existing gold standard 2004 guidelines in a cohort of Indian patients. This was a descriptive study of cases referred to the department of Pathology for bone marrow examination with suspicion or diagnosis of HLH from Jan 2015 to June 2017. The clinical records of these patients were analysed and diagnosed as positive and negative for HLH using the HLH 2004 guidelines and HScore, the scoring system developed by Fardet et al. Fifty cases fulfilled the inclusion criteria. The variables fever, hepato and /or splenomegaly, high triglyceride levels and marrow hemophagocytosis are highly significant to predict an individuals risk of HLH. We propose a cut-off of ≥ 166 for the diagnosis of HLH by using HScore. If 4 of the 7 criteria are fulfilled by HLH 2004 guidelines, there is an 80% probability of having HLH by HScore. The HScore is less restrictive in confirming a diagnosis of HLH compared to the HLH 2004 guidelines. HScore is a simple, and cost effective tool for diagnosis of reactive HLH. The higher the HScore, more is the probability of HLH.

IgG4-related lymphadenopathy masquerading as Hodgkin lymphoma: lessons from a pathologist's desk.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder affecting multiple organ systems. The awareness of this disease has tremendously increased over the last decade leading to effective treatment and decreased morbidity to the patients. Histopathology plays an important role in the diagnosis of IgG4-RD, and definite histologic criteria are proposed in clinically suspected patients. We report a patient with multiple organ system involvements of the salivary gland, lymph node and kidney. IgG4-related lymphadenopathy (IgG4-RL) in this patient was misdiagnosed as nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). Refractoriness to treatment for NLPHL and subsequent manifestations of renal involvement lead us to the correct diagnosis of this potentially treatable condition. IgG4-RL can mimic reactive proliferation as well as lymphomas. We report the clinical presentation and discuss the problems faced by pathologists in diagnosing IgG4-RL. We believe that awareness of this rare presentation will enhance the knowledge in diagnosing IgG4-RD.

Subcutaneous Phaeohyphomycosis: A Clinical Mimic of Skin and Soft Tissue Neoplasms-A Descriptive Study from India.

BACKGROUND: Phaeohyphomycosis is a fungal infection caused by heterogenous group of fungi known as phaeoid or dematiaceous fungi. It manifests in four clinical forms-cutaneous, subcutaneous, systemic and cerebral phaeohyphomycosis. The subcutaneous form is the most common presentation. Clinically these subcutaneous swellings resemble benign skin and soft tissue neoplasms like lipoma, sebaceous cyst or neurofibroma. Histopathology serves as a very useful tool in diagnosing these cysts by identifying the fungal elements. METHODS: A retrospective review of all cases diagnosed as phaeohyphomycosis in the department of Pathology at a tertiary care centre in South India over 9 years (January 2009-December 2017) was done. The clinical, histopathological findings of these cases were reviewed and analysed. RESULTS: Sixty-six cases of subcutaneous phaeohyphomycosis were reported during the 9 year period. Sixty-two per cent of these patients were diagnosed as skin and soft tissue neoplasms. In 94% cases, the extremities were affected. Multiple cysts were seen in 11% of patients. Fine needle aspiration cytology was done in 29 cases with fungal hyphae identified in all cases on cytology. CONCLUSION: Subcutaneous phaeohyphomycosis mimics benign skin and soft tissue neoplasms clinically. Histopathological examination along with cytology plays a major role in diagnosis of phaeohyphomycosis and thus helps in appropriate patient management.

Granulomatous Response in Intracranial Germinomas: Diagnostic Problems.

Intracranial germinomas are rare and account for <0.5% of primary intracranial tumors. In contrast to the gonadal germinomas, these do not show granulomatous response within the tumor. In rare cases, the granulomatous component may obscure the tumor proper and lead to diagnostic difficulties/dilemmas. We report a case of suprasellar germinoma in a 17-year-old boy which showed granulomatous response. We discuss the differentials to be considered in such a scenario and discuss the utility of squash cytology and immunohistochemistry in these lesions.

Emphasizing the pivotal role of fine-needle aspiration cytology in a case of recurrent malignant chondroid syringoma.

Fine-needle aspiration cytology (FNAC) features of malignant chondroid syringoma (MCS) are rarely documented. Here, we report a case of recurrent MCS, highlighting its interesting clinicopathologic features. Initially, we received cytology and histopathology slides (for review) of a 57-year-old woman who had undergone resection for an occipital MCS and later presented with recurrence. On reviewing the slides, cytology was consistent with recurrent MCS. However, tissue sections showed features of a malignant epithelial tumor with comedonecrosis and sebaceous differentiation owing to which a diagnosis of metastatic adenocarcinoma/malignant adnexal tumor was suggested. Due to an ambiguous histology, a repeat FNA was performed to perform immunocytochemistry (ICC) and oil-red O stains, which confirmed the diagnosis of MCS with sebaceous differentiation. Thus, in a situation where histology was inconclusive due to lack of representative sections, FNAC played a major role in resolving the diagnostic dilemma and facilitating an appropriate clinical management.

A rare case of congenital Ewing sarcoma/PNET of the scapula.

Ewing sarcoma (ES)/primitive neuroectodermal tumors (PNET) are known to occur at both central and peripheral locations, as well as at skeletal and extraskeletal sites. They most commonly occur in the first 2 decades of life. We report a rare case of congenital Ewing sarcoma/primitive neuroectodermal tumor arising from the scapula.

Basal like carcinoma of breast in patient with neurofibromatosis I: an association or co-existence?

Neurofibromatosis I (NF I), an autosomal dominant disorder is associated with increased risk of benign and malignant peripheral nerve sheath tumors and central nervous system tumors. There are only few case reports of breast carcinoma in known patients of NF I. We report a case of basal like carcinoma of the breast in a 69-year-old lady who had NF I. Considering the rare association of carcinomas with NF I and finding that both the NF I gene and a breast cancer pre-disposition gene, BRCA 1 are located in close proximity on chromosome 17q makes the association of these two conditions intriguing.