A scoping review of vasculitis as an immune-related adverse event from checkpoint inhibitor therapy of cancer: Unraveling the complexities at the intersection of immunology and vascular pathology.

BACKGROUND/PURPOSE: Vasculitis as an immune-related adverse event (irAE) from checkpoint inhibitor therapy (ICI) to treat cancer is a rare clinical event, and little is known regarding its nosology, clinical manifestations, or response to treatment and outcomes. METHODS: To address these gaps, we used the Preferred Reporting Items for Systemic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework to further define this complication. Two independent PUBMED searches in September and November of 2022 revealed 127 publications with 37 excluded from title by relevance, 43 excluded by article type, and 23 excluded due to lack of biopsy results, or biopsy negative for vasculitis. Twenty-nine documented cases from 24 publications were included for final analysis. Basic demographics, ICI details, timing of onset of vasculitis symptoms, irAE treatment and outcomes were collected. The vasculitides were classified using 2022 ACR/EULAR Vasculitis Classification Criteria as well as 2012 Revised Chapel-Hill Nomenclature. Adaptations from Naidoo et al. 2023 [1] consensus definitions for irAEs were used and efforts were made to classify steroid-responsive versus unresponsive irAEs. RESULTS: Of the 29 cases reviewed, the average age of patients was 62.1 ± 11.0, composed of 58.6 % (n = 17) male and 41.3 % (n = 12) female. Prominent cancer types were lung cancer (41.4 %; n = 12), melanoma (41.4 %; n = 12), and renal cancer (10.3 %; n = 3), with majority being stage 4 (75.9 %, n = 22) and stage 3 (10.3 %, n = 3). Only 8 cases met the ACR/EULAR criteria, and by Chapel-Hill Nomenclature, approximately a third were small-vessel vasculitis (31.0 %; n = 9) with n = 4 positive for ANCA. Most biopsies were taken from the skin (37.9 %, n = 11) and kidney (24.1 %, n = 7). Patients were either treated with single (65.5 %, n = 19), dual (17.2 %; n = 5), or sequential (17.2 %; n = 5) ICI regimen which included anti-PD-1 therapy in all but one case, with mean of 8.7 ± 10.5 cycles received. Mean time to onset of symptoms from start of ICI was 7.2 ± 7.8 months, with 55.2 % occurring >3 months since the initial immunotherapy. Vasculitis treatment included glucocorticoids in 96 % of cases and immunotherapy was often discontinued (44.8 %; n = 13). Clinical improvement of irAE was documented in 86.2 % (n = 25). Data were missing in terms of fate of ICI (34.5 %; n = 10) and tumor outcomes (41.4 %; n = 12). Cancer progressed in 20.7 % (n = 6), stable in 34.5 % (n = 10) cases, and 6 patients died of all-causes. CONCLUSION: Vasculitis as an irAE appears clinically heterogeneous and rare. Among reported cases with adequate documentation, vasculitis is of delayed onset following the initiation of immunotherapy. Outcomes of ICI-vasculitis were generally favorable, responding to glucocorticoids and immunotherapy withdrawal. There is an urgent need for more standardized reporting of rare irAEs such as vasculitis to clarify clinical risks, classification, relationship to immunotherapy and outcomes.

Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium.

PURPOSE: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS. CONCLUSION: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Acute Liver Failure From Sickle Cell Hepatopathy Treated With Exchange Transfusion.

Sickle cell disease (SCD) is a qualitative hemoglobinopathy that can cause widespread sickling and vaso-occlusive events in all organ systems. Sickle cell hepatopathy is an umbrella term for various acute and chronic pathologies of the liver as a result of sickling in SCD patients. We present below the case of a 49-year-old woman who had an acute liver failure in the setting of a hepatic crisis with recovery after exchange transfusion. Hepatic involvement in SCD may be life-threatening. Understanding the etiology and severity of hepatic involvement by sickling is necessary for appropriate treatment.

Yet another utility for isocitrate dehydrogenase.1: Can it serve as an immunomarker to assess tumor margins in gliomas?

BACKGROUND: Isocitrate dehydrogenase-1 (IDH1) mutation is now an established early event in gliomagenesis. The ability to detect this mutation by several techniques including immunohistochemistry makes it a significant marker for diagnosing and prognosticating gliomas. This study was done to assess the expression of mutant IDH1 in different grades of gliomas and evaluate its utility in differentiating reactive gliosis from glioma and defining surgical margins of these tumors in the operative specimens. MATERIALS AND METHODS: A total of fifty cases including equal number of Grade I, II, III, and IV gliomas and gliosis were included in the study. Formalin-fixed, paraffin-embedded tissue sections from these lesions were immunostained with IDH1 and Ki-67 antibody, and percentage of tumor cells that stained positive with these markers was assessed. RESULTS: Grades II, III, and IV showed consistent immunopositivity for IDH1. No immunostaining was noted in Grade I glioma and gliosis. Mean Ki-67 labeling index correlated with grades of gliomas with low activity in Grade I and high activity in Grade IV. Individual tumor cells infiltrating into adjacent normal brain parenchyma also stained positive with IDH1 antibody. CONCLUSION: Immunostaining for IDH1 mutation can be utilized as a reliable marker in the precise diagnosis of diffuse gliomas and also in objective assessment of surgical margins to differentiate gliomas from gliosis.

Olmesartan Associated Enteropathy: A Rare Underdiagnosed Cause of Diarrhea and Weight Loss.

BACKGROUND Olmesartan, an angiotensin receptor blockade class of antihypertensive medication has recently been associated with a seronegative sprue like enteropathy. Patients typically present with diarrhea and weight loss often prompting exhaustive diagnostic workup. Discontinuation of the drug leads to dramatic recovery and hence, physicians need to be aware of olmesartan associated enteropathy (OAE) in order to avoid unnecessary testing. CASE REPORT A 59-year-old Caucasian male was admitted to the hospital with complaints of intractable diarrhea, vomiting and considerable weight loss. Medical history was notable for hypertension being treated with olmesartan. Workup for all potential infectious causes and celiac disease was negative. Eventually, a colonoscopy was performed due to his persistent symptoms and biopsy revealed lymphocytic colitis. An upper endoscopy was also performed, and histopathology of the duodenum revealed total villous blunting. In light of negative serology for celiac disease and after a detailed review of the patient's medications, the possibility of olmesartan induced enteropathy was considered. Olmesartan was stopped and his symptoms resolved. A follow-up endoscopy done a few months later showed normal small bowel mucosa. CONCLUSIONS This case demonstrates the need for a thorough medication review by healthcare providers especially after a full workup for the patient's symptoms has already been performed. It also reiterates that having an awareness of rare side effects of common medications mitigates the need for extensive diagnostic testing.

Spinal epidural abscess caused by a community acquired extended spectrum beta lactamase producing Klebsiella pneumonia.

Spinal epidural abscess (SEA) can be a medical and surgical emergency. It is encountered in patients with epidural catheter placement, paraspinal injections, diabetes mellitus, alcoholism, HIV infection, trauma, contiguous bony or soft tissue infection, intravenous drug use, hemodialysis, or overt bacteremia, but may occur spontaneously associated with a presumed silent bacteremia. We report here, a case of extensive SEA due to a community-acquired extended spectrum beta lactamase (ESBL)-producing Klebsiella pneumoniae in a diabetic patient. This case highlights the importance of stringent antimicrobial stewardship and also the need for prompt diagnostic evaluation, and early surgical decompression in order to prevent morbidity and mortality.

Gall Bladder Agenesis: A Rare Embryonic Cause of Recurrent Biliary Colic.

BACKGROUND Gallbladder agenesis (GA) is an extremely rare anatomic anomaly with a reported incidence of less than 0.5%. It is usually asymptomatic, but can present with features of biliary colic and cholecystitis. We present here a case of GA in a patient with recurrent biliary colic.  CASE REPORT A 24-year-old African American woman presented with recurrent episodes of right upper-quadrant abdominal pain. During her first episode, she was found to have elevated transaminases and clinical features of cholecystitis, but ultrasound did not visualize a gallbladder and she was discharged with a diagnosis of biliary colic. She returned within a week with worsening liver enzymes, severe pain, and vomiting. A hepatobiliary iminodiacetic acid (HIDA) scan was done, which again did not show the gall bladder. On clinical suspicion of acute cholecystitis, she underwent laparoscopic surgery. Intraoperatively, the gall bladder fossa was empty and a diagnosis of gall bladder agenesis was made. She presented a third time with similar complaints and magnetic resonance cholangiopancreatography (MRCP) was done, which showed normal biliary tract anatomy and absent gall bladder. A diagnosis of sphincter of Oddi dysfunction was made and she was discharged on antispasmodics. CONCLUSIONS Diagnosing GA is challenging. The rarity of this entity combined with classic clinical features of cholecystitis and non-visualization of the gall bladder on routine investigation prompts unnecessary surgical intervention. Awareness of this condition, along with use of better imaging modalities like preoperative MRCP, can aide physicians to appropriately manage this uncommon clinical condition.

Persistent or recurrent Castleman's disease - Look out for a lurking lymphoma!

Castleman's disease, a rare condition of uncertain etiology clinically presents in isolated form or as a multicentric disease. The multicentric form can develop malignancies such as Kaposi's sarcoma or lymphomas. We present a case of Castleman's disease with coexisting interfollicular Hodgkin's lymphoma that was confirmed by immunohistochemistry. This case report highlights the fact that an occult lymphoma has to be ruled out in persistent or recurrent Castleman's disease.

Study of endometrial pathology in abnormal uterine bleeding.

INTRODUCTION: Abnormal uterine bleeding (AUB) is the commonest presenting symptom in gynaecology out-patient department. Endometrial sampling could be effectively used as the first diagnostic step in AUB, although at times, its interpretation could be quite challenging to the practicing pathologists. This study was done to evaluate histopathology of endometrium for identifying the endometrial causes of AUB. We also tried to observe the incidence of various pathology in different age groups presenting with abnormal uterine bleeding. MATERIAL AND METHODS: This was a study done at Sri Ramachandra Medical College and Research Institute, Chennai, India on 620 patients who presented with AUB from June 2005-June 2006. Out of which 409 cases of isolated endometrial lesions diagnosed on histopathology were selected for the final analyses. A statistical analysis between age of presentation and specific endometrial causes was done using χ(2) test. RESULTS: The most common age group presenting with AUB was 41-50 years (33.5%). The commonest pattern in these patients was normal cycling endometrium (28.4%). The commonest pathology irrespective of the age group was disordered proliferative pattern (20.5%). Other causes identified were complications of pregnancy (22.7%), benign endometrial polyp (11.2%), endometrial hyperplasias (6.1%), carcinomas (4.4%) and chronic endometritis (4.2%). Endometrial causes of AUB and age pattern was statistically significant with P value <0.05. CONCLUSION: There is an age specific association of endometrial lesions. In perimenopausal women AUB is most commonly dysfunctional in origin and in reproductive age group, one should first rule out complications of pregnancy. The incidence of disordered proliferative pattern was significantly high in this study, suggesting an early presentation of these patients.

Pathology of synovial lipomatosis and its clinical significance.

BACKGROUND: Synovial lipomatosis is a rare disorder of the synovium, commonly affecting the knee joint, resulting in joint pain, swelling, and effusion. The etiology of this condition still remains unclear. AIM: This was a study done to evaluate the disease process in synovial lipomatosis, with respect to the clinical parameters and pathological features. MATERIALS AND METHODS: Case files of synovial lipomatosis diagnosed on histopathology between 2007 and 2009 were perused, to study the case history, and tissue sections were reviewed for the histomorphological changes. RESULTS: Eight cases of synovial lipomatosis were diagnosed on histopathology from year 2007 to 2009, of which one occurred in the wrist joint and the rest were localized to the knee joint. Age ranged from one year to seventy-three years, with a male preponderance. Pain and swelling were major complaints. Three had a significant past history, one occurring post-trauma, one following chikungunya, and another with septic arthritis. Three of the cases had osteoarthritis. Body mass index was elevated in four cases and one case had protein energy malnutrition. On histopathological examination, all the cases showed villous proliferation of the synovium, with focal and diffuse infiltration by mature adipocytes. Four cases showed focal hyperplasia of the lining epithelium and five cases revealed variable fibrosis. CONCLUSION: Synovial lipomatosis may mimic tumorous, lesion-like synovial lipoma or hemangioma and its distinct histomorphology helps in distinguishing it from these lesions. It possibly represents a secondary phenomenon following the degenerative process of articular disease of the joints.

Solid variant of papillary carcinoma of nipple: an under recognized entity.

Papillary lesions of the breast represent a heterogeneous group with differing biological behavior. Solid papillary carcinomas are uncommon tumors composed of circumscribed large cellular nodules separated by bands of fibrosis. Correct diagnosis is crucial but may be difficult, as many other benign and malignant lesions have similar histological appearances. Immunohistochemistry plays a useful role in their differentiation. We describe one such case of a solid variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had no other palpable mass in rest of the breast tissue. The case is documented for the rarity of its occurrence and significance of recognition of this lesion.

Challenges in neurosurgical intraoperative consultation.

BACKGROUND: Intraoperative consultation for neurosurgical specimens can be difficult at times, despite the use of both frozen section and squash preparation. Various factors influence the diagnostic accuracy of these procedures. This study was conducted to evaluate reasons for discordant case results in neurosurgical intraoperative consultations and make a comparative analysis of these two commonly used methods to identify the possible pitfalls, errors, and limitations. MATERIALS AND METHODS: All the neurosurgical cases received in the Department of Pathology for intraoperative consultation over a period of 3 years were studied retrospectively. The slides of frozen sections and squash preparation were retrieved and the diagnosis was compared with the final diagnosis given on paraffin-embedded sections. RESULTS AND OBSERVATIONS: A total of 6% of the cases were found to be discordant; these included angiomatous meningioma, Non-Hodgkins lymphoma, metastatic renal cell carcinoma, cerebellopontine angle fibrous meningioma, and craniopharyngioma. Highly vascular lesions, unavailability of squash preparation in a few cases and technical errors like thick smears, excessively crushed specimen, freezing, and cautery induced and crushing artifacts contributed to misdiagnosis. CONCLUSION: The discrepant cases need to be reviewed regularly by pathologists to familiarize themselves with the morphological changes and artifacts. The knowledge of possible errors could minimize misinterpretation and help in providing a more conclusive opinion to the operating surgeon.

Autofluorescence: a screening test for mycotic infection in tissues.

Fungal infection is a major health concern as the clinical features are not very distinctive. Lack of rapid diagnostic techniques results in delay in diagnosis, which may even culminate in a fatal outcome. The fact that many pathogenic fungal organisms autofluoresce in hematoxylin and eosin (H and E)-stained sections under ultraviolet illumination led us to evaluate the role of autofluorescence as a rapid screening technique for fungal infections. The aim of the present study was to assess the value of autofluorescence as a screening method for detecting fungi on tissue sections and to compare the results of autofluorescence with conventional histochemical stains for fungi. Hematoxylin and eosin-stained slides of mycotic lesions were examined under fluorescent microscope and the findings were compared with results of Gomori's methenamine silver and periodic acid-Schiff stains. We found fungal autofluorescence in 63 out of 64 cases studied, with a sensitivity of 97.8% and specificity of 100% in comparison with fungal stains. This was statistically significant (P < 0.05). We conclude that autofluorescence can be used as a rapid screening method for identification of fungi in tissue sections as it does not require any other specialized staining procedure.

Sellar lesion: not always a pituitary adenoma.

Inflammatory lesions of the hypophysis account for 0.5% of all symptomatic diseases of the pituitary, which include lymphocytic hypophysitis, granulomatous hypophysitis with or without specific etiology and pituitary abscess. Sellar tuberculoma is a rare type of granulomatous hypophysitis. We document a case of a postmenopausal lady who presented with galactorrhea, headache and blurring of vision. Based on preliminary investigations, a clinical diagnosis of pituitary adenoma was made and the pituitary gland was surgically excised. Histopathological examination showed caseating granulomas, along with normal areas of preserved pituitary gland and a final diagnosis of tuberculous hypophysitis was made. This case is being documented due to the extremely rare involvement of the pituitary gland by granulomatous lesions such as tuberculosis and to emphasize the role of intraoperative consultation to obviate the need for radical surgery in such lesions.

Angiomatous meningioma: a diagnostic dilemma.

Angiomatous meningioma accounts for 2.1% of all meningiomas. It has features of a typical benign meningioma with many small or large vascular channels which may predominate over its meningothelial elements. We present here a series of three cases of angiomatous meningioma, which posed diagnostic difficulty to clinicians, radiologists, and pathologists. All the three cases showed a tumor entirely composed of thin-walled vascular channels and cells with bland morphology in the background. The diagnosis was confirmed by immunohistochemistry. We present series of three cases to highlight the histomorphological features of this uncommon variant of meningioma that could help in distinguishing it from hemangioblastoma and hemangiopericytoma.