Multifocal Oral Epstein–Barr Virus-Positive Mucocutaneous Ulcers Associated with Dual Methotrexate and Leflunomide Therapy: A Case Report

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unique clinicopathologic entity of lymphoproliferative disorder, occurring in immunosuppressed patients. Due to its rarity, EBVMCU may be under-recognized by clinicians as well as pathologists. In addition, its clinical and histopathologic features overlap with other benign and malignant conditions, making a diagnosis challenging. This report presents an unusual case of multifocal oral EBVMCUs in a 52-year-old female patient with rheumatoid arthritis, receiving the combination of methotrexate and leflunomide for 5 years. The patient presented with persistent multiple large painful ulcers involving her palate and gingiva for 6 months. The histopathologic examination revealed extensive ulceration with diffuse polymorphic inflammatory infiltrate admixed with scattered atypical lymphoid cells showing occasional Hodgkin and Reed/Sternberg-like cell features. These atypical cells showed immunoreactivity for CD20, CD30 and MUM1/IRF4. EBV-encoded small RNA in situ hybridization was positive, validating the presence of EBV-infected cells. Two months after discontinuation of both immunosuppressive medications, oral lesions gradually regressed. At 9-month follow-up, no evidence of relapsing oral EBVMCU has been observed. The multifocal presentation of EBVMCU is rare and could be resulted from the overwhelming immune suppression by long-term use of dual immunosuppressants. Its diagnosis requires comprehensive correlation of patient history, clinical findings, histopathologic, and immunophenotypic features. The ability of EBVMCU to regress following removal of immunosuppressive causes is in drastic contrast to a variety of its potential clinical and histopathologic mimics. Therefore, accurate diagnosis is crucial to avoid unnecessary patient management and achieve optimal patient outcomes.

Psoriasiform Mycosis Fungoides Involving the Face- A Rare Case Report

Mycosis fungoides is represented as the most common epidermotropic cutaneous T-cell lymphoma, which is mainly characterized by the proliferation of atypical cells within the epidermis. We report a rare presentation of mycosis fungoides in a 60-year-old male presenting with chronic psoriasiform plaque involving the face. Punch biopsy of the lesion from the forehead was taken for routine histological examination and immunohistochemical stains. Results of biopsy and immunohistochemical findings were consistent with mycosis fungoides and diagnosed as psoriasiform presentation of mycosis fungoides involving the face.

Pleomorphic lipoma: A rare entity

Pleomorphic lipoma is a rare neoplasm that is considered as a variant of spindle cell lipoma. It predominantly occurs in the dermis or subcutis of the posterior neck, upper back, and shoulders. Pleomorphic lipoma may clinically present as a slow-growing and well-circumscribed subcutaneous mass. Though it is a benign tumour it may contain atypical cells for which it may mimick sarcoma or other malignant soft tissue tumours. So histopathological diagnosis is vital for preventing unnecessary surgery. Here we report a case of a pleomorphic lipoma on upper back in a 55yr old patient.

Deciduoid Mesothelioma of Peritoneum Masquerading as Peritoneal Carcinomatosis.

Mesothelioma is an insidious neoplasm that develops from mesothelial cells. About 80 % of mesotheliomas originate in the pleural cavity. Other sites where it has been reported are the peritoneal cavity, tunica vaginalis, and the pericardium. A 45-year-old female presented with complaints of abdominal distention and pain for three months. Physical examination revealed signs of wasting of the appendicular and axial skeleton muscles, loss of subcutaneous fat, and hollowing of the eye sockets. There was pitting edema in the bilateral lower limbs. Per abdomen, examination revealed abdominal distension with umbilicus in the midline. On palpation, gross ascites was present, and no organomegaly, definitive mass, or lump was palpable. On percussion, the dull note was heard all over the abdomen, and fluid thrill was appreciated. The ascitic fluid examination revealed the presence of atypical cells. Omentectomy was done and sent for histopathological examination.The specimen of omentectomy was in multiple fragments and measured 17x16x3cm. Few of the fragments were nodular, soft to firm. On serial slicing, the cut section was gray-white with areas of necrosis. Microscopic examination showed sheets of malignant cells. These tumor cells were immunoreactive to EMA, Cytokeratin, Vimentin, Calretinin, WT-1, and D2-40 and immunonegative to Desmin (highlighting only the entrapped reactive mesothelial cells), Inhibin, BerEP4, TTF-1, CD 68, Napsin, ER, CEA, CDX2, PR, PAX-8, and SALL4. Ki 67 labelling index was 15%. The features were of Malignant Mesothelioma, Deciduoid variant. Deciduoid mesothelioma is a rare subtype with a poor prognosis. So, the mesothelioma should be distinguished from deciduosis.

Absolute Lymphocyte Count Expansion Kinetics Can be Utilized to Assess Response to CAR T Cell Products

Introduction CAR T-cell therapies are utilized to treat relapsed/refractory B-lymphoblastic leukemia (B-ALL), diffuse large B cell lymphoma, mantle cell lymphoma, and multiple myeloma. CAR T cell expansion kinetics after infusion impact response. However, these CAR T cell products vary in their target epitope and constituent molecules that makes it difficult to validate broad molecular or flow cytometric assays for use in the clinical setting. The lack of commercially available reagents also limits the ability of clinical laboratories to validate separate CAR T cell specific assays. We investigated the utility of common hematology laboratory parameters to measure CAR T cell expansion and response. Methods Clinical hematology laboratory parameters after infusion of autologous and allogeneic CAR T cell products directed were assessed. Concurrent CBC and cell population data (CPD) parameters from the Sysmex XN 3000 automated hematology analyzer were available in 82 patients. Absolute lymphocyte count (ALC) kinetics after infusion of autologous CD19, allogeneic CD19, CD22, CD33, allogeneic CD123-directed CAR T cell products were analyzed. Patients who received bone marrow transplant served as controls. CPD parameters included X (lateral light scatter-granularity), Y (fluorescence-nuclei acid content), Z (forward scatter-size), and their distribution widths WX, WY, WZ. Archived CellaVision cell morphology images from 118 patients who received CD19-directed CAR T cell products and 25 patients who received other CAR T cell products were analyzed. Response was determined from 1 month post-CAR bone marrow disease assessment. Results Absolute Lymphocyte Counts, lymphocyte morphology and cell population data after infusion of CAR T cell products CD19-CAR, UCAR19, and CD22-CAR all showed a distinct lymphocyte expansion phase post-infusion in responders (Figure 1A) that was absent in non-responders and controls(Figure 1B). ALC showed characteristic lag, expansion, and contraction phases in responders. CD19-CAR had a peak at day 8 while CD22-CAR and allogenic Universal(U)CAR19 had relatively delayed peak times occurring near day 15 (Figure 1B). The stem cell transplant control patients did not show ALC expansion in the first two weeks and instead showed normal lymphocyte regeneration that occurs in the third to fourth weeks. CD33-CAR and allogeneic UCAR123 non responders did not show ALC expansions. CAR T cell responders showed a distinct sequence of changes in lymphocyte morphology that was absent in non-responders and stem cell transplant controls (Figure 1C). This pattern was noted uniformly across various CAR T cell products (Figure 1D-1F). The morphological changes were categorized as: early, mid, and late. Early atypical cells were noted around days 4-8 after infusion and showed immunoblastic morphology that was present in 89% (n=105) of patients. Mid atypical cells were noted around days 5-14 after infusion and showed atypical large granular lymphocyte morphology that were seen in 95% (n=112) of patients. Late atypical cells showed the typical LGL morphology and was seen in 82% (n=97) of patients. WY fluorescence, which is a measure of nucleic acid content, was most useful in assessing changes in lymphocytes after CAR T cell infusion. WY was low (mean 402, n=57) at baseline pre-infusion timepoint and peaked (mean 1207) approximately 1 week after infusion (mean 7.9 days, n = 59). Peak WY was observed 3.7 days prior to peak ALC (mean day 11.6, n = 59). Conclusion We demonstrate for the first time that common clinical laboratory parameters can be used to follow CAR T cell expansion after infusion in various autologous and allogeneic CAR T cell products. ALC expansion is a measure of CAR T cell expansion after infusion and correlates with response. Responders showed higher peak ALC compared to non-responders in all CAR T cell products. Timing of peak ALC expansion was determined by other factors such as expression of target antigen and CAR T-cell product used. Lymphocyte morphology followed ALC changes and showed a consistent sequence of changes that was seen across multiple CAR T cell products. Finally, CPD parameter WY which is a measure of nuclei acid content and activation, was an early harbinger of ALC expansion. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

PATHOLOGICAL STUDY OF BODY FLUIDS IN A TERTIARY CARE CENTER IN SOUTH INDIA.

Body cavities uid analysis is done routinely in both clinical pathology and cytology departments of Pathological laboratory. Any imbalance between uid 1. formation and removal leads to effusion, as stated by Starling's law The peritoneal, pleural, cerebrospinal and pericardial uids comprise the major chunk of 2 body uids . Accumulation of uid in various body cavities can occur in vast range of benign conditions and it also a frequent clinical presentation and complication of malignant disorder. METHODS: A prospective study was conducted in the Department of Pathology, Osmania general hospital Hyderabad, Telangana, India, during January 2020 to December 2020 and analyzed 880 uid samples collected from patients for cell count and cytology. The data collected was tabulated using Microsoft excel and analyzed using standard statistical tools. RESULTS -Of total 880 uids analyzed peritoneal uid (42%) constitutes the major type of uid sent frequently for analysis followed by cerebrospinal uid (41%) with male to female ratio of 1.9:1. 62.7% of uids had clear gross appearance . Of total 880 uid samples analyzed 649 samples (73.7%) had shown lymphocyte predominance. Of total 880 uids samples analyzed 9 samples (1%) were found positive for atypical cells, conrmed on cytology suggesting there malignant origin. CONCLUSION: uid aspiration from body cavities constitutes one of the common day care procedures for clinicians. Effusion uid analysis is key in delineating the background cause in the patient ranging from reactive, inammatory and malignant conditions. Fluid cell count coupled by cytological analysis of uids in pathology laboratory is a time tested tool having good sensitivity and specicity when interpreted along with biochemical parameters.

Case report of three distinctive pulmonary toxicities related to durvalumab (PD-L1 inhibitor) consolidation therapy in locally advanced non-small cell lung cancer

Immunotherapy has become part of the standard of care in the treatment of locally advanced non-small cell lung cancer. However, immunotherapy is associated with immune-related pneumonitis and radiation-related adverse effects. Pulmonary-related toxicity after definitive chemoradiotherapy can be challenging to distinguish from disease progression, especially in the setting of additional immunotherapy after radiation. Our patient is a 61-year-old male that was diagnosed with stage IIIA lung adenocarcinoma of the right upper lobe that underwent treatment with concurrent chemoradiation and adjuvant durvalumab. He was found to have fevers, shortness of breath, generalized body aches and dry cough. His influenza test was positive for Influenza A. On imaging, there was significant hypermetabolic enlargement of multiple lymph node stations underwent bronchoscopy with biopsies of the right upper lobe, station 4R and 7 lymph node. Pathology of the right upper lobe biopsy showed fragments of bronchial epithelium with rare atypical cells present. Pathology of the station 7 lymph node showed small non-necrotizing granulomas, and station 4R showed rare atypical cells, consistent with squamous metaplasia. The patient was started on high dose prednisone for treatment of immune related pneumonitis and continue follow up in clinic. His symptoms continued to improve continued interval improvement seen on serial imaging in the right upper lobe soft tissue changes within the field of prior radiation in addition to improvement in the mediastinal and hilar lymphadenopathy, consistent with immunotherapy related Sarcoidlike granulomatous reactions.

Apoptosis of Circulating Heterophils; Implications for the Interpretation of the Heterophil/Lymphocyte Ratio

The aim is to demonstrate a variety of apoptotic heterophils (equivalents of mammalian neutrophils) occurring in hemograms of 50 apparently healthy pullets housed in cages. These atypical cells are found in blood with normal total white cell levels (TWBC, ~20K) and in those ranging up to 100(K) a leukocytosis/leukemoid reaction level. Conversely heterophil/lymphocyte (H/L) ratios in all hens ranged between 0.14 – 0.50 (homeostasis). The Arneth index (a heterophil age measure) of 1.8 computed using only intact heterophils indicated a “left-shift”, suggesting inflammation even in the context of a normal hemogram.

Rice Bodies In The Wrist

Rice bodies are a rare finding in medicine and remain to be a challenge to provide adequate treatment. As occurrence varies over multiple rheumatic as well as infectious diseases, multiple hypotheses have been made about their origin. While rice bodies are most frequently reported in the shoulder and knee joints, flexor tendon synovitis with accompanying rice bodies is more rare. We report a case of extensive flexor tenosynovitis with rice bodies in the wrist in a 90-year old patient with seronegative rheumatoid arthritis. The patient reported a 5 month history of painful swelling of the right wrist. Ultrasound showed pronounced swelling of the synovial tissue of the flexor digitorum tendons as well as the flexor pollicis longus tendon. Laboratory test were negative for rheumatology tests with normal CRP and sedimentation rates. T2 weighted MRI demonstrated an extensive synovitis reaching from the distal forearm into the hand with inclusions, better known as rice bodies. Synovectomy including carpal tunnel release was performed with dissection of the mass revealing an extensive synovitis with a multitude of rice bodies. Histopathology showed lymphohistiocytic infiltrates consistent with rheumatoid nodules, no atypical cells were discovered. After surgery the patient regained full function of the wrist within two weeks without any remaining pain or mass in the affected limb.

Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis

Background: Adipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL) comprising the majority of cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL.Methods: Fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog (MDM2) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Papanicolaou, and evaluated for 12 cytological parameters by six cytotechnologists.Results: The findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with MDM2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in the lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%), and therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting the diagnosis of ALT/WDL. FISH of MDM2 on Papanicolaou-stained specimens was performed in four cases. In two cases, the results were similar to those of MDM2 FISH performed on FFPE sections and were reproducible, whereas in two other cases, the signal could not be evaluated because of the strong background coloration. Conclusions: Cytology specimens may be useful for preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Papanicolaou-stained specimens and the detection accuracy of MDM2 amplification can be improved.