Assessing IgG4-related ophthalmic disease and its mimics: a comparison of ACR/EULAR, organ-specific and revised comprehensive diagnostic criteria.

AIMS: Diagnosis of IgG4-related ophthalmic disease (IgG4-ROD) rests on the correlation of clinical features, serological testing and histopathology, using internationally accepted diagnostic criteria for objective interpretation; however, several mimickers of IgG4-RD overlap in clinical presentation and histopathology. We assess histopathological features in a series of presumptive IgG4-ROD cases, with emphasis on histopathological mimics and comparison of three IgG4-ROD diagnostic/classification criteria (organ-specific (OS), revised comprehensive diagnostic (RCD) and American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria). METHODS: The histopathology database was screened for cases with clinical/histopathological suspicion of IgG4-ROD. Slides were reviewed, OS, RCD and ACR/EULAR criteria were applied, and the final clinicopathological diagnosis was recorded. RESULTS: 37 patients (24 females, 13 males; 19-73 years) were diagnosed as either IgG4-ROD (n=18) or non-IgG4-related disease (n=19). Non-IgG4-related disease group showed elevated serum IgG4 (55.5%), fibrosis (100%), dense lymphoplasmacytic inflammation (92.8%), with an increase in tissue IgG4+plasma cells (57.1%) and elevated IgG4:IgG+plasma cell ratio (14.3%). ACR/EULAR missed 50% (9/18, sensitivity-52.8%) of true IgG4-ROD cases, while OS and RCD criteria missed 11.1% (2/18, sensitivity-88.9%) of IgG-ROD cases. ACR/EULAR criteria mislabelled 7.14% (1/14, specificity-90.9%) while OS and RCD criteria wrongly categorised 71.4% (10/14, specificity-47.4%) and 50% (7/14, specificity-63.2%) specific non-IgG4-ROD cases as IgG4-ROD. Storiform fibrosis, obliterative phlebitis, increased IgG4:IgG+plasma cell ratio and elevated serum IgG were statistically significant in distinguishing IgG4-ROD from its mimics. CONCLUSION: ACR/EULAR criteria showed high specificity but were cumbersome and sensitivity was low, while RCD and OS criteria showed low specificity. Stringent clinicopathological correlation to exclude mimics is critical in avoiding diagnostic errors in IgG4-ROD.

Benign Lesion of the Common Bile Duct Mimicking a Malignant Tumor: an Entity Commonly Overdiagnosed Clinically.

Adenomyomatous hyperplasia and adenomyoma are rare benign inflammatory pseudotumors of the gallbladder arising from Rokitansky-Aschoff sinuses. Occurrence of these hyperplastic conditions in the Vaterian and biliary system is extremely rare and is a concern for gastroenterologists and surgeons in distinguishing them from primary malignancies of the biliary system. Definitive diagnosis by imaging or cytopathological examination is difficult; thus, surgical resection becomes the only choice in such cases to relieve the obstruction. Here, we report two extremely rare cases of adenomyomatous hyperplasia of the extrahepatic bile duct after an extensive diagnostic workup, followed by Whipple's procedure.

Evaluation of the follicular patterned thyroid lesions based on the WHO 2022 criteria with an emphasis on the grey-zone lesions.

Follicular-patterned thyroid nodules (FPTN) are classified byWHO-2022 into benign, borderline and malignant categories. There are however, grey-zone lesions that pose a diagnostic challenge due to ambiguity in defining criteria and inter-observer variability. WHO-2022 has enumerated specific diagnostic criteria for these lesions. Accurate categorization of morphologically similar TNs is vital to reduce overtreatment of indolent lesions. In this study, we have reclassified FPTNs according to WHO-2022 criteria, emphasizing on grey-zone lesions. We studied the utility of immunohistochemistry (IHC)-CD56, HBME-1 and CK19 in distinguishing benign from malignant nodules and BRAFV600E IHC to better distinguish the (widely-invasive) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) from infiltrative FVPTC. Only those cases with dominant nodule having follicular pattern histology were included and re-evaluated for following histopathological features-focality, encapsulation, circumscription, nuclear PTC features, capsular-invasion, angio-invasion, papillae and necrosis. IHC findings for above-mentioned markers were noted. Seventy-nine cases met the inclusion criteria. Amendment of original diagnosis was done in 19 % cases. BRAFV600E IHC was positive in the two cases of infiltrative FVPTC while it was negative in all nine IE (invasive encapsulated) FVPTCs. Diffuse HBME1 was noted in most malignant nodules (61 %) while CD56 was expressed more often in benign lesions (70 %). CK19 was positive in lesions displaying nuclear PTC features (86 %). Using WHO 2022 criteria, we were able to re-classify follicular thyroid lesions with greater confidence. Appropriate IHC panel in adjunct to histology aids in categorizing challenging cases.

A Case of Medullary Carcinoma of Colon Morphologically Resembling Non-Hodgkin's Lymphoma.

Medullary carcinoma of the colon is an unusual and unique histologic subtype of colorectal cancer. It is strongly associated with microsatellite instability, most commonly loss of MLH1 indicative of deficient mismatch repair proteins. Diagnosis is challenging as they do not display the usual histological pattern. Immunohistochemical staining also shows unusual findings like negativity for CD20 and CDX2. Here, we explore an intriguing case of medullary carcinoma of colon which showed loss of MSH2 and MSH6 and a morphology reminiscent of Non-Hodgkin's lymphoma.

A Curious Case of Omental Oxalate Crystals in a Patient With Struma Ovarii: Pointers to an Unusual Clinicopathological Scenario.

Percutaneous image-guided biopsies are becoming increasingly common in routine pathology practice, with the greater omentum emerging as a common target. We present herein an account of a middle-aged lady with a complex ovarian mass, omental thickening, and raised serum CA125; clinically suspected to have advanced ovarian malignancy. Fine needle aspiration cytology (FNAC) from the ovarian mass was inconclusive. Omental biopsy revealed only refractile, birefringent crystalline material with surrounding foreign body giant cell reaction; thus surprising the clinical team. Subsequent resection of the ovarian mass showed a teratoma composed exclusively of thyroid tissue, diagnosed as struma ovarii. The omental crystals, interpreted as calcium oxalate crystals, were possibly a consequence of colloid seeding during the ovarian mass FNAC.

Concomitant Langerhans and Interdigitating Reticulum Cell Hyperplasia in a Reactive Lymph Node of an Infant with Omenn Syndrome: A Diagnostic Pitfall for Langerhans Cell Histiocytosis.

Omenn syndrome, a rare form of combined immunodeficiency in infants, presenting with recurrent infections, erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and increased serum IgE levels. It is a fatal condition unless treated by hematopoietic stem cell transplant. Hence, an early diagnosis and a prompt treatment can lead to better outcome in these unfortunate babies afflicted with Omenn syndrome. Here, we present an 8-week-old infant with typical features of Omenn syndrome, both clinically as well as on laboratory analysis, but surprising immunohistochemical findings on lymph node biopsy.

Extrapelvic "Uterus Like Mass" Following Laparoscopic Morcellation Hysterectomy - a Consequence of Iatrogenic Implantation?

Uterus-like mass is a rare form of endometriosis, which shows striking structural similarity to the normal uterus. Formation of a mass lesion raises clinical concern for malignancy, and pathologic examination is necessary for accurate diagnosis. We describe herein, a middle aged woman who presented with a mesenteric mass six years post hysterectomy, which was initially suspected to be a gastrointestinal stromal tumor. The resected was specimen was grossly pear shaped with microscopy showing a central endometrial glands and stroma lined cavity, surrounded by a thick muscular wall reminiscent of uterine myometrium. Histogenesis of this entity is unclear, and several theories are proposed regarding the etiology, including congenital anomaly theory, metaplasia and heterotopia theories. Our clinical scenario developed a few years after uterine morcellation, indicating a possibility of another "iatrogenic implantation" theory behind the pathogenesis of this rare lesion.

Liver abscesses caused by visceral larva migrans: Aimless wanderer separated from the host.

Visceral larva migrans (VLM) is a systemic zoonotic parasitic disease caused by migration of the second stage larva through viscera of humans. Despite being a foremost public health problem in low- and middle-income countries (LMICs) such as India, larva migrans remains an untended zoonosis. Here, we report two cases of VLM who presented with fever and abdominal pain for a prolonged duration. On further investigation, marked peripheral eosinophilia with multiple confluent necrotizing eosinophilic granulomas were identified on histopathological examination of the liver.

Inflammatory myofibroblastic tumor of colon and duodenum: Metachronous, metastatic or local recurrence? An unusual presentation.

ABSTRACT: Inflammatory myofibroblastic tumor (IMT) is a tumefactive proliferation of spindled myofibroblastic cells admixed with inflammatory infiltrate. This tumor has a predilection for the involvement of visceral soft tissues and has a tendency for local recurrence. Occurrence of metastatic or metachronous IMTs is a rare presentation. We report a rare case of a 50-year-old man with metastatic IMTs in the colon and duodenum.

Retrospective histopathology audit of thymectomy specimens: A clinicopathological study of 303 cases spanning the non-neoplastic, benign and malignant spectrum.

Aims: Thymectomy specimens are uncommon in routine histopathology practice. However, awareness of various pathologic entities and definite reporting of these specimens is paramount to optimal patient management. Our objective was to determine the histomorphologic spectrum of thymectomy specimens spanning the non-neoplastic, benign to malignant spectrum. Methods and Results: Thymectomies received over an 8-year period were retrospectively analyzed by reviewing clinical details and histologic findings in detail, incorporating the latest World Health Organization (WHO) 2015 histologic classification. A total of 303 thymectomy specimens (179 males/124 females, mean age 45.3 years [3-84 years]) were included. Around 51.2% (n = 155) patients had associated myasthenia gravis (MG), while 17.5% (n = 53) had incidentally detected anterior mediastinal mass (AMM). Non-neoplastic and benign pathologies comprised 31% (n = 94) cases and showed stronger association with MG (P = 0.009). Thymic follicular hyperplasia (TFH) was the commonest non-neoplastic pathology (n = 32), while the benign tumor group included thymic hemangioma/lymphangioma, thymolipoma, and ectopic parathyroid adenoma. Thymic epithelial tumors (TETs) comprised 64.7% cases, with majority being thymomas (185/303; 61.1%). Thymoma type B2 was the commonest histologic subtype and Stage I/T1 was the most frequent stage. Type A and AB thymomas affected older patients (P = 0.005) and were in lower stage (both Masaoka and American Joint Committee on Cancer [AJCC]) than type B thymomas (P = 0.007). No significant association between MG and thymoma subtype, patient sex or Masaoka stage was seen (P > 0.05). Thymic carcinomas comprised 11 cases and showed no association with MG (0/11, P < 0.001); squamous cell carcinoma was the commonest histologic type (8/11; 72.7%). Conclusion: TETs are the commonest thymic lesions; however, a diverse spectrum of pathologic processes can affect the thymus.

Glomus Tumor of Scrotum and Stomach: Usual Tumor at Unusual Locations.

Glomus tumor is a rare benign neoplasm, accounting for less than 2% of all the soft tissue tumors. Although they can develop in any part of the body, they commonly do so in upper extremities, most commonly in fingers. Here, we report two cases of glomus tumor at rare locations, in order to increase the awareness of this tumor entity in unusual sites. We also highlight the clinicopathological features and differential diagnoses of this tumor.

Common Variable Immunodeficiency Enteropathy and Its Unpredictable Biopsy Findings: Not Everything Is Black and White.

Common variable immunodeficiency syndrome (CVID) is a diverse entity characterized by hypogammaglobinemia and a propensity for recurrent infections. Involvement of the gastrointestinal tract has a variable manifestation ranging from asymptomatic involvement to florid signs and symptoms. Due to these incongruous findings, multiple concurrent biopsies are to be done for tissue diagnosis. Here, we present two cases diagnosed with CVID on the basis of clinical findings, lab investigations, and morphological features on biopsy.

Diverse liver morphology in two cases of visceral leishmaniasis: Same face, different expressions.

Two cases of visceral leishmaniasis are presented; one patient was from an endemic region and visceral leishmaniasis was suspected clinically, while the other was from a non-endemic region and it was not suspected clinically. Bone marrow examination was negative in both cases and both showed different morphological pictures in the liver biopsies. These are discussed. Importance of travel history is also highlighted even if it is in distant past.

Proliferative fasciitis arising from the abdominal wall: A rare tumour excised by laparoscopy.

Proliferative fasciitis (PF) is a rare pseudosarcomatous lesion arising from the subcutaneous fascia and the fibrous septa. Only few hundred cases have been reported in the literature. In the largest series of 53 patients, only two patients had PF lesion arising from the flank. The most common site of origin is extremities followed by abdomen and head and neck. Its origin from the abdominal wall layer and presentation as the fever has been rarely reported in the literature. A PF lesion larger than 5 cm dimension has been sparsely noted. We report the presence of this rare entity in a 68-year-old gentleman who presented to us with low-grade fever and the presence of large lump arising from the abdominal wall. In our patient, the lesion was arising from transervsalis fascia and was excised in toto laparoscopically without damaging the abdominal muscles. It is imperative to differentiate both these lesions from sarcoma on histopathological examination as the follow-up treatment protocols for both vary.

Cutaneous ectopia of lung, located on back and neck: Hitherto undescribed presentation.

Ectopia is defined as the presence of a normal-appearing tissue in an abnormal location, where it is not normally found. In the literature, it is also referred to as heterotopia and is described as choristoma when it forms a mass. Lung tissue ectopia is a rare anomaly and is characterized by the presence of mature lung tissue comprising well-formed bronchi, bronchioles, and alveoli at an abnormal location. Occurrence of ectopic lung tissue in the skin is an extremely rare entity and the diagnosis is mostly established by histopathologic examination. This report documents a rare occurrence of cutaneous ectopic lung tissue at two locations (neck and back). Cutaneous ectopia at multiple sites has not been described in the literature till date.

Spectrum of presentation in primary anorectal malignant melanoma and its management.

The article presents a series of four patients with primary anorectal melanoma presenting to our institute between 2016 and 2021. The primary objective of the series is to give an overview of the variable presentation of this rare entity from a high-volume colorectal tertiary care centre in a developing country. The patients ranged in age from 55 to 73 years and were mostly women (except one). The clinical presentation varied from bleeding per rectum to tenesmus and mucus in stools, overlapping with those of inflammatory bowel disease and primary anorectal adenocarcinoma. All patients were treated with surgery (laparoscopic or open), ranging from local excision to abdominoperineal resection. All our patients had a good outcome after surgery with no mortality at 30 or 90 days after surgery. The article aims to present a comprehensive overview of the various options of management with evidence from the surgical literature.

Interdigitating dendritic cell sarcoma of pleura, diagnostic challenges of a rare disease.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare subtype of dendritic cell tumour. The solitary lymph node disease is most commonly seen, but may occasionally present extranodally in skin, intestines, soft tissue, liver or spleen. Here we present a case of IDCS in pleura in 53-year-old man, who presented with loss of appetite and chest pain. The initial biopsy was inconclusive. The patient was started on anti-tubercular treatment considering the higher prevalence of the disease in this part of the world. However, the symptoms worsened after 2 months and repeat PET-CT scan revealed extensive FDG avid lesions in the multiple sites in the body. Repeat PET guided biopsy confirmed this rare IDCS neoplasm. Diagnostic challenges of this rare tumour are discussed.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Evaluation of Anorectal Malignant Melanoma: A Case Series.

Melanomas are the malignancies that can affect any anatomic region where melanocytes exist (such as the epidermis, eyes, nasal cavity, and anus). Anorectal melanoma is a rare mucosal melanocytic malignancy, comprising 0.8% of all anorectal malignancies. Here, we report a case series of three patients of anorectal melanoma and role of positron emission tomography/computed tomography in diagnosis and follow-up to evaluate the local recurrence and distant metastases. Of three patients, two presented with rectal bleeding and one with obstruction. One patient had recurrence after 10 months, other after 24 months, and third remained disease free post surgery till 9 months.