ALK-Negative Primary Cutaneous Anaplastic Large Cell Lymphoma With Systemic Involvement or Systemic ALCL With Cutaneous Lesion. A Diagnostic Dilemma.

ABSTRACT: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.

Mucosal Schwann Cell Hamartoma of the Gall Bladder.

Mucosal Schwann cell hamartoma (M-SCH) of the intestinal mucosa is a rare entity and incidental finding in histological examination. Histological characteristics are Schwannonian cell proliferation in lamina propria with S100-positivity. M-SCH-like lesion in the gall bladder is even rarer and is a recently reported entity. We report this extremely rare lesion in a cholecystectomy specimen of a 4-year-old boy, which makes it the youngest patient to be having M-SCH-like lesion in the gall bladder.

Primary extranodal NK/T cell lymphoma of stomach: A case report and review of literature.

ABSTRACT: Extranodal Natural killer/T (NK/T) cell lymphoma nasal type is an aggressive non-Hodgkin lymphoma and has a constant association with Epstein-Barr virus (EBV) infection. Approximately more than 75% cases are located in upper aero-digestive tract, of which stomach is a very rare site. Very few cases of gastric extranodal NK/T cell lymphoma have been reported in the literature. A 22-year-old male patient presented with complaints of abdominal pain and hematemesis. Endoscopy showed a large ulcer in the stomach. Partial gastrectomy done and histopathology showed transmural infiltration by intermediate size atypical lymphoid cells which are immunopositive for CD3, CD56, TIA, EBV-encoded RNA (EBER) and negative for CD4, CD8, CD20. A diagnosis of extranodal NK/T cell lymphoma nasal type was made.

Malignancy-Associated Sarcoid-Like Reaction in a Case of Triple-Negative Breast Cancer on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

We describe the case of a 54-year-old woman with triple-negative breast cancer whose baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed hypermetabolic left breast primary, ipsilateral axillary lymphadenopathy, lung nodules, and mediastinal lymph nodes. Histopathological examination of tissue from mediastinal lymph nodes confirmed a diagnosis of sarcoid-like reaction. Chemotherapy may induce or cause a flare-up of malignancy-associated sarcoid-like reaction. However, in our patient's post-chemotherapy F-18 FDG PET/CT, there was reduction in size and uptake of the mediastinal lymph nodes along with partial response shown by the other lesions. We aim to describe this rare course of malignancy-associated sarcoid-like reaction and highlight the role of F-18 FDG PET-CT in such cases.

Splenic Lymphomas: A Tertiary Care Center Experience and Review of Literature.

Primary splenic lymphomas are rare with the majority of lymphomas in spleen being secondary to an extra-splenic lymphoma. We aimed to analyze the epidemiological profile of the splenic lymphoma and review the literature. This was a retrospective study including all splenectomies and splenic biopsies from 2015 to September 2021. All the cases were retrieved from Department of Pathology. Detailed histopathological, clinical and demographic evaluation was done. All the lymphomas were classified according to WHO 2016 classification. A total of 714 splenectomies were performed for a variety of benign causes, as part of tumor resections and for the diagnosis of lymphoma. Few core biopsies were also included. A total of 33 lymphomas diagnosed in the spleen, primary splenic lymphomas constituted 84.84% (n = 28) of the cohort with 5 (15.15%) having the primary site elsewhere. The primary splenic lymphomas constituted 0.28% of all the lymphomas arising at various sites. Adult population (19-65 years) formed the bulk (78.78%) with a slight male preponderance. Splenic marginal zone lymphomas (n = 15, 45.45%) comprised of major proportion of cases followed by primary splenic diffuse large B-cell lymphoma (n = 4, 12.12%). Splenectomy was the main course of treatment for SMZL with a good overall outcome, with chemotherapy ± radiotherapy forming the mainstay in other lymphomas. Lymphomas in spleen can be infiltrative or a primary, hence proper clinic-radiological and pathological evaluation is required. Appropriate management is guided by the precise and detailed evaluation by the pathologist, requiring understanding of the same.

Follicular Helper T-Cell-derived Nodal Lymphomas: Study of Histomorphologic, Immunophenotypic, Clinical, and RHOA G17V Mutational Profile.

The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.

Neoplasms of follicular helper T-cells: an insight into the pathobiology.

T-follicular helper cells (TFH) are a unique subset of T-cells with varied transcriptional profiles and functions. In the last 2016 WHO classification, lymphomas arising from TFH were included as a broad category and emphasis was given to separating them from other peripheral T cell lymphomas. The neoplasms derived from these mainly comprise angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma with T-follicular helper cell phenotype, follicular T-cell lymphoma, and cutaneous CD4+ small-medium sized lymphoproliferative disorders. The TFH lymphomas comprise both indolent and aggressive forms. Additional immunohistochemistry to identify TFH cells like CD10, BCL6, ICOS, PD1, CXCL13 and mutations like RHOA, IDH2 is required for diagnosis and prognostication. The understanding of these has evolved over the years, and currently we review the updates and pathobiology of the above.

Plasma cells in oral lesion: A clue to diagnosis or a diagnostic dilemma.

Objective: Plasma cells can just represent a part of host inflammatory response or form the cornerstone of diagnosis such as IgG4-related disease (IgG4RD) and plasma cell dyscrasias and sometimes create a diagnostic dilemma. The study aims to discuss a series of plasma cell lesions which we encountered in the oral cavity, discuss the diagnostic conundrum of plasma cell lesions. We also propose a working classification for their interpretation. Materials and Methods: All plasma cell lesions affecting the oral and maxillofacial region were retrieved from the archives of the Department of Oral and Maxillofacial Pathology. The cases were analyzed on the basis of histomorphology and immunohistochemical markers along with clinical, imaging and laboratory findings. Results: Thirteen (0.64%) of 2026 oral lesions were diagnosed with plasma cell lesions. Out of 13 cases, 9 were plasma cell gingivitis, 2 IgG4-RD, 1 plasma cell myeloma and 1 plasmablastic lymphoma. Representative case from each category is discussed along with one case of well-differentiated squamous cell carcinoma (WDSCC) masquerading as plasma cell dyscrasias. Conclusion: We discuss the practical difficulties faced during the diagnosis of these oral plasma cell entities along with a working classification and propose an efficient diagnostic scheme for the correct characterization of these lesions.

Small cell variant anaplastic large cell lymphoma presenting as leukemia: A case report and review of Literature.

Anaplastic large cell lymphoma (ALCL) is a subcategory of the mature T-cell neoplasm characterized by sheets of cluster of differentiation (CD)30-positive pleomorphic large cells mostly present as lymphadenopathy. Here, we describe a case of Small cell variant ALCL with leukemic presentation without lymphadenopathy. A 68-year-old male presented with fatigue and weakness; examination revealed a total leukocyte count of 295,000/uL. The peripheral smear showed cells having cerebriform nuclei comprising 90% of the leukocytes. The flow cytometry showed that the cells were immunopositive for CD3 (weak), CD4, CD7, and negative for the rest of the markers. The cell blocks from the peripheral blood showed cells with immunopositivity for CD30, anaplastic lymphoma kinase (ALK), and Epithelial membrane antigen (EMA). A diagnosis of the small cell variant of ALK-positive ALCL was made. Due to the presence of atypical pleomorphic cells without lymphadenopathy, the case has a diagnostic dilemma with differential diagnosis of Sezary syndrome, T-cell prolymphocytic leukemia, and adult T-cell leukemia/lymphoma. Karyotyping and additional immunohistochemistry help for the confirmation of the diagnosis.

Cytology of Castleman's disease (hyaline-vascular type) masquerading as Hodgkin's lymphoma.

Castleman disease (CD) is a rare benign disorder presents as a lymph nodal mass in mediastinum, cervical, axillary or abdomen. Due to the presence of dysplastic dendritic cell in a background mature lymphocyte and plasma cell, it mimics Hodgkin disease (HD). Synchronous and metachronous occurrence in HD and CD can also occur. An 11-year-old male presented with cervical lymphadenopathy (3.5 × 3.5 cm). Fine needle aspiration shows atypical binucleate cell in a background of small lymphocytes, a diagnosis of Hodgkin disease is suggested. Excisional biopsy showed classical features of Hyaline vascular Castleman disease. Careful cytological evaluation and clinical correlation is required for definitive diagnosis.

Incidentally Detected High SSTR Expression in Uterine Leiomyoma on DOTANOC PET/CT.

ABSTRACT: A 38-year-old woman with a 2-month history of per vaginal bleeding and episodes of palpitations, headache, and vomiting underwent 68Ga-DOTANOC PET/CT for evaluation, which revealed a left suprarenal mass and a large uterine mass, both of which were intensely tracer avid. Histopathology of the masses after surgery revealed a left pheochromocytoma and uterine leiomyoma. SSTR-expressing leiomyoma is an uncommon finding and must be kept in mind as a differential diagnosis of DOTANOC-avid uterine mass.

Renal Epithelioid Angiomyolipoma in Children.

Renal angiomyolipoma is a rare cause of renal tumor in children. Most are associated with tuberous sclerosis, and the classic type is observed more commonly. Epithelioid angiomyolipoma is even rarer with only limited case reports and series published in literature, most of which are of adult patients. We describe a 12-year-old boy, a diagnosed patient of tuberous sclerosis, who presented with pain in the left flank. On evaluation, it was found to have a left renal mass with the clinical picture suggestive of renal cell carcinoma. Partial nephrectomy was performed and histopathology revealed epithelioid angiomyolipoma. The child was asymptomatic at follow-up after 3 months. Only a few such cases in children are found in literature, which are discussed alongside. Differential diagnosis of this rare tumor must be kept in mind in a renal tumor as surgery is generally curative in this possibly malignant tumor. Metastasis confers a poor prognosis. Chemotherapy is generally not effective, although various regimens have been tried. Tumor recurrence must be kept in mind and a follow-up after apparent complete remission is of paramount importance.

Lymphoma subtypes in India: a tertiary care center review.

Lymphomas are a group of neoplasm arising from immune cells with varied clinical presentation, molecular profile, morphology and immunophenotype. The epidemiology and response to treatment varies among patients from different geographical locations. We analyze the demographic characteristics of lymphomas in a tertiary care center of India over a period of five years. This was a retrospective study including cases from 2015 to 2019 which were classified according to WHO classification 2017. A total of 4115 lymphoma cases were diagnosed. Hodgkin lymphomas (HL) comprised 30.35% (n = 1249), and non-Hodgkin lymphoma (NHL) was 69.65% (n = 2866). Site of presentation was nodal in 64.76% cases, and 35.23% were extranodal. There was an overall male predominance. Among the NHLs, B-cell type comprised of 84.08% and 15.38% was T- and NK cell lymphomas. Mature B cell lymphomas comprised 82.41% with predominant being diffuse large B cell lymphoma type (42.53%) followed by follicular lymphoma (10.81%) and small lymphocytic lymphoma (6.10%). Among the T-cell type, PTCL NOS (2.65%) was the predominant subtype followed by ALK positive anaplastic large cell lymphoma (ALCL-ALK+) (2.44%), extranodal NK-T cell lymphoma (2.02%) and others. Classical type was predominant type (97.91%) among HL, and 2.08% were nodular lymphocyte predominant type. Among the classical HL, nodular sclerosis (28.1%) and mixed cellularity (32.18%) co-dominated. Our study indicates that the Indian population differs in the prevalence, presentation and the subtyping among various lymphomas. Higher prevalence of Hodgkin lymphoma, DLBCL, ALK + ALCL and immature cell neoplasm was noted.

Pediatric mediastinal lymphoma.

The mediastinum is the visceral compartment of thoracic cavity divided into the superior and inferior mediastinum, further inferior compartmentalize into anterior, middle, and posterior mediastinum. Lymphoma in the mediastinum may be primary or secondary to systemic disease. Lymphoma may arise from lymphoid organs-like thymus, mediastinal lymph nodes or other mediastinal organs like heart, lung, pleura, and pericardium. It comprises about 12% of all the mediastinal tumors in adults however, it constitutes 50% of the pediatric mediastinal mass. Anatomically lymphoma most commonly involves anterior mediastinum. Among the pediatric mediastinal lymphomas, lymphoblastic lymphoma (LBL) predominate followed by Hodgkin lymphoma (HL), primary mediastinal large B cell lymphoma (PMBCL) and very rarely Grey zone lymphoma. Other types of non-HLs (NHLs) are rare among pediatric population. Radiologically and clinically present as an anterior mediastinal mass with symptoms of dyspnea, cough, and superior vena cava syndrome. Also, clinically and radiologically all the pediatric mediastinal mass shares the overlapping features, hence, for treatment and prognostic points of view its essential to differentiate the three entities, i.e., LBL, HL and PMBCL. The pathological diagnosis of pediatric mediastinal lymphomas is quite challenging for general histopathologists. In this review, we describe the pathology, genetics, differential diagnosis, treatment, prognosis, and a simplified histopathological and immunophenotypical approach to differentiate the pediatric mediastinal lymphomas.

Lymphoma versus thymoma: A diagnostic challenge.

T-cell acute lymphoblastic lymphoma is a common hematological malignancy of childhood. It can involve the bone marrow, blood, or tissues like the thymus, lymph nodes as well as extra-nodal sites. Two aspects of the disease make early diagnosis critical - the clinically aggressive nature of the neoplasm, and availability of effective chemotherapy against the disease. Diagnosis is largely based on clinical suspicion and confirmation by histopathological examination of the affected tissue. However, biopsy results may not always be helpful in establishing the diagnosis. We describe the case of an 18-year old patient presenting with fever and an anterior mediastinal mass suspected to have a T-cell lymphoma where an initial biopsy from the mass had features of a thymoma. The patient was kept in close follow up for 2 months when there was a recurrence of symptoms and a repeat bone marrow evaluation revealed a T-cell lymphoma.

Perineuritis or infiltration of optic nerve sheath? A presentation of diffuse large B cell Gastric lymphoma.

Optic perineuritis is an inflammatory disorder involving the optic nerve sheath. It is currently considered as a part of idiopathic orbital inflammatory disease which also includes dacryoadenitis, orbital myositis, superior orbital fissure, and cavernous sinus syndrome (Tolosa hunt syndrome). As it is idiopathic, it is considered a diagnosis of exclusion. Another important differential is optic nerve lymphoma. Isolated optic nerve lymphoma associated with systemic involvement has been described in literature. We report a case that presented as third nerve palsy but later on developed central retinal vein occlusion and was ultimately diagnosed as primary gastric lymphoma of diffuse large B cell type.

Clinicopathological Profile of Castleman's Disease in Indian Population: Experience From a Tertiary Care Center.

Castleman's disease (CD), also known as angiofollicular lymph node hyperplasia, a rare, non-malignant chronic lymphoproliferative disease characterized by, uni or multicentric lymphadenopathy. There is limited information about the clinicopathological variations and associations of this entity. A total of 50 cases of CD were retrieved from the archives, between the years 2005-2017. The cases were divided into pediatric (0-18 years), young adult (age ≤ 40 years) and older adult groups (age > 40 years respectively). Detailed clinicopathological correlation was done. The age range was 6-74 years. There was a male predominance (M: F-1.6:1). The majority (72%; 36/50) of the patients were adults; 46% young adult and 28% older adult, while only 28% (14/50) were of pediatric. Majority (78%) showed features of unicentric Castleman disease (UCD) while rest 22% presented with multi centric Castleman disease (MCD). Systemic symptoms were more frequent in MCD as compared to UCD cases (p = 0.06). The majority of the cases (40/50; 80%) were of the hyaline vascular type. Two of the cases showed mixed histological feature. Out of 50 patients 29 patient's treatment details are available. Majority unicentric cases were cases surgically excised 14/17 (82.3%). Three patients 3/17 (17.6%) were treated with chemotherapy. In multicentric Castleman's disease group, six of the 12 cases with MCD were managed by chemotherapy. One patient died of progressive disease. Castleman disease has varied clinical presentation and is often associated with other diseases. A high degree of suspicion and careful histological examination is required in order not to miss this entity.

Role of Voriconazole in the Management of Invasive Central Nervous System Aspergillosis: A Case Series from a Tertiary Care Centre in India.

Invasive central nervous system (CNS) aspergillosis is acquired by either hematogenous dissemination or direct spread from a sinus infection. We describe a series of nine patients with CNS aspergillosis from a tertiary care teaching institute in North India who were treated with voriconazole alone or in combination with surgery. All patients who had clinical and radiological features consistent with fungal CNS infection, showed the presence of septate hyphae on histopathology/microscopy and were either culture positive for Aspergillus spp. or had serum galactomannan positivity were diagnosed as CNS aspergillosis. Clinical features, risk factors, diagnostic modalities, treatment details and outcome at last follow-up were recorded for all patients diagnosed with CNS aspergillosis. A total of nine patients were diagnosed with CNS aspergillosis. The median duration of presentation at our hospital was six months (IQR-2-9 months). Six patients had concomitant sinus involvement, while two patients had skull-base involvement as well. All patients were treated with voriconazole therapy, and three of these patients underwent surgery. All but one patient survived at the last follow-up (median duration was 14 months (IQR- 8-21.5). Two patients had complete resolution, and voriconazole was stopped at the last follow-up, and the rest of the patients were continued on voriconazole. Of the six patients who were continued on voriconazole, all but one had more than 50% radiological resolution on follow-up imaging. Invasive CNS aspergillosis is an important cause of CNS fungal infection that is often diagnosed late and requires long-term voriconazole-based therapy.

Brain abscess in patients with chronic kidney disease: A case-based approach to management in resource-limited settings.

The management of patients with brain abscess poses a significant challenge to clinicians in patients with chronic kidney disease. Obtaining a biopsy sample from the affected area is the mainstay in the diagnosis, but it is often unavailable. In most cases, therapy is guided by clinical findings and imaging alone. We discuss three cases of brain abscess- each with a different scenario and discuss the issues faced in management. The first case was a 32-year-old post-renal transplant male patient with a brain abscess due to dematiaceous fungi and was treated with amphotericin. The second case was a 42-year-old female patient with stage 5 chronic kidney disease on maintenance hemodialysis who presented with a brain abscess due to suspected fungal infection based on imaging findings and was managed with antibiotics and voriconazole. The third case was a 42-year-old post-renal transplant male patient who presented with a brain abscess due to nocardiosis and was managed with cotrimoxazole, meropenem and linezolid. We also summarize the approach to the management of brain abscess in resource-limited settings.