Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

OBJECTIVE: Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. METHODOLOGY: 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. RESULTS: The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. CONCLUSION: Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

Unveiling the Rarity: CD20 Expression in Mycosis Fungoides and Its Clinical Significance.

ABSTRACT: Although CD20 expression is typically scarce in mycosis fungoides (MF), it is more commonly associated with T-cell lymphomas. Nevertheless, isolated instances of CD20-positive MF have been documented infrequently. Here, we present a unique case of CD20-positive MF in a 30-year-old man who manifested with a hypopigmented patch on the anterior chest. Histopathological examination revealed epidermotropic infiltrates of small- to medium-sized lymphocytes with hyperchromatic and cerebriform nuclei aligned along the basal and low-mid layers of the epidermis. Immunophenotypic analysis demonstrated neoplastic T cells expressing CD4+, CD8+, and CD3+ with the loss of CD7. Intriguingly, a notable subset of the neoplastic T cells exhibited CD20 expression. This case contributes to the sparse literature on CD20-positive MF and underscores its diagnostic and clinical ramifications. The role of B cells has been more thoroughly characterized in T-cell lymphomas other than MF. However, its significance in MF remains unclear due to the scarcity of reported cases. Some hypotheses propose that the B cells' expression might indicate immune dysregulation or complex interactions within the tumor microenvironment. Another perspective suggests it could signify a progression of the disease towards a more aggressive lymphoma phenotype. Further investigation and documentation of similar cases is imperative to elucidate the clinical features, prognosis, and optimal therapeutic strategies. The long-term prognosis and outcomes in patients with hypopigmented MF and CD20 positivity remain ambiguous, underscoring the necessity for continued research and scrutiny of analogous cases.

Navigating Diagnostic and Therapeutic Challenges in Primary Cutaneous Gamma/Delta T-Cell Lymphoma: A Case Study of Fatal Outcomes Within Two Months.

ABSTRACT: Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is a rare yet highly aggressive subtype of primary cutaneous lymphoma. Characterized by its challenging diagnosis and poor prognosis, PCGD-TCL presents unique clinical and histopathological features that distinguish it from other primary cutaneous lymphoma subtypes. Here, we report the case of a 75-year-old man who initially presented with multiple erythematous indurated plaques over his back and bilateral lower extremities. The initial biopsy suggested primary cutaneous T-cell lymphoma (PCTCL) with a CD30-negative phenotype. However, within a 2-month interval, the disease progressed rapidly, manifesting as extensive skin involvement across the chest and upper extremities. A repeat skin biopsy was performed, revealing dermal atypical lymphocytes without epidermotropism. Immunohistochemical analysis demonstrated positivity for CD3, CD5, and CD4, as well as T-cell receptor delta (TCR delta) expression, along with the loss of CD8 and CD30 expression. These findings were consistent with a diagnosis of PCGD-TCL. Despite therapeutic interventions, including systemic treatments, the patient's condition deteriorated rapidly, ultimately leading to his demise within a month of receiving the PCGD-TCL diagnosis. This case highlights the diagnostic complexities associated with PCGD-TCL, emphasizing the importance of careful histopathological examination and immunophenotypic characterization. Given its aggressive nature and propensity for rapid dissemination, early recognition of PCGD-TCL is paramount for initiating appropriate therapeutic interventions. However, effective treatment options for PCGD-TCL remain limited, and the disease typically carries an unfavorable prognosis. Further research is needed to elucidate the underlying molecular mechanisms driving the pathogenesis of PCGD-TCL, to identify novel therapeutic targets, and to improve patient outcomes. In addition, increased awareness among clinicians and pathologists regarding the clinical presentation and diagnostic criteria of PCGD-TCL is crucial for facilitating timely diagnosis and management of this challenging malignancy.

Fumarate Hydratase-Deficient Abdominal Wall Leiomyoma Presenting a Decade Post-Fumarate Hydratase-Deficient Uterine Leiomyoma Excision: An Incidental or Syndromic Association?

Background. The occurrence of fumarate hydratase-deficient leiomyoma of the abdominal wall is exceptionally rare. Case Presentation. A 50-year-old female patient with a past medical history of fumarate hydratase-deficient uterine leiomyoma presented with a left lower quadrant abdominal mass that has been present for the past 2 years. An ultrasound revealed a 3.5 cm oval hypoechoic mass. A subsequent CT scan showed a 3.5 cm hyperdense mass within the left internal oblique musculature. No family history is noted. A biopsy of the mass exhibited bundles of spindle cell neoplasm exhibiting bizarre ovoid nuclei and eosinophilic cytoplasm. No evidence of mitotic figures or tumor necrosis was noted. Immunohistochemical staining showed positive staining for desmin and smooth muscle actin (SMA), but negative staining for MART-1, S100, and CD34. Lesional cells showed expression of 2-succinocysteine and loss of fumarate hydratase expression. A diagnosis of fumarate hydratase-deficient leiomyoma was rendered. Conclusion. This report reinforces the importance of considering genetic testing for fumarate hydratase mutations in the evaluation of extra-uterine leiomyomatous lesions. Comprehensive follow-up and clinical screening in individuals with new lesions and a known history of fumarate hydratase-deficient neoplasms is mandatory. Recent recommendations support the integration of morphology-based evaluation along with immunohistochemical staining and genetic testing as a part of the standard evaluation for all uterine leiomyomas.

Unveiling the Uncommon: Gastrointestinal Basidiobolomycosis of the Colon and its Distinctive Splendore-Hoeppli Phenomenon.

BACKGROUND: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. CASE PRESENTATION: A 53-year-old man from Saudi Arabia with a known history of diverticulosis presented with severe abdominal pain and diarrhea. A CT scan revealed circumferential wall thickening of the descending and sigmoid colon with surrounding fat stranding, suggesting a diagnosis of complicated diverticulitis. Additional thick fluid was observed around the affected area. Surgical excision was pursued. A gross examination of two received large bowel segments disclosed marked ulcerated mucosa and wall thickening with exudate-covered serosal surfaces and adhesions. Microscopic examination unveiled significant infiltration by eosinophils, polymorphonuclear leukocytes, and granulomatous inflammation. Thin-walled, broad fungal hyphae of Basidiobolus, surrounded by eosinophilic material, were identified. Granulomas displayed abundant multinucleated giant cells and palisading histiocytes around central necrosis or abscess formation. Thin-walled, broad fungal hyphae of Basidiobolus, with sparse septations, are surrounded by a radiating, intensely eosinophilic cuff (Splendore-Hoeppli phenomenon). These hyphae, visible with hematoxylin and eosin staining, were further highlighted with periodic acid-Schiff and Gomori methenamine silver staining. DISCUSSION: Basidiobolomycosis may mimic neoplastic lesions. Histologically, the characteristic features include broad, thin-walled septate hyphae surrounded by eosinophilic material, a finding that is accentuated by the Splendore-Hoeppli phenomenon. Microscopic examination, along with special stains such as periodic acid-Schiff (PAS) and Gomori methenamine silver, is essential for accurate diagnosis. CONCLUSION: Prompt recognition and appropriate antifungal therapy are vital for favorable patient outcomes. This report highlights the distinctive features of Basidiobolomycosis to raise awareness and understanding of this infrequent yet clinically significant fungal infection.

Delayed Diagnosis of SMARCA4-Deficient Undifferentiated Tumor in a Heavy Smoker Male Patient: Discovered Through Bone Sampling, with Extensive Distant Metastases and Concurrent Granulomatous Disease, Leading to Patient Fatality.

Background. SMARCA4-deficient undifferentiated tumors are rare and pose a diagnostic challenge. This study delves into the intricate diagnostic terrain of SMARCA4-deficient undifferentiated tumors, providing insights into their diverse clinical presentations and diagnostic approaches. Case Presentation. A 69-year-old heavy-smoker man with adalimumab-treated rheumatoid arthritis presented with multiple lesions. A CT scan revealed a spiculated lung mass, enlarged mediastinal lymph nodes, and hepatic lesions. A whole-body FDG-PET/CT scan revealed heterogeneous hypermetabolic lesions in the lung, liver, and bone. Initial two core needle liver biopsies and a left upper lobe lung wedge resection initially indicated steatohepatitis and granulomatous formation with no evidence of malignancy. Several months later, the patient returned with left-sided flank pain and significant weight loss. CT scan identified a thigh mass, adrenal lesion, and extensive multiple skeletal lesions. A biopsy of the thigh mass revealed an extensively necrotic, epithelioid-to-spindled cell neoplasm with positive staining for pan keratin, focal staining for CD56, and a loss of nuclear expression of SMARCA4. A final diagnosis of SMARCA4-deficient undifferentiated tumor was rendered. Unfortunately, the patient's condition deteriorated, and he died a few weeks after receiving the final diagnosis. Conclusion. SMARCA4-deficient undifferentiated tumors have emerged as recent subjects of medical study, distinguished by their unique morphology and SMARCA4-deficient immunohistochemistry. These tumors present diverse clinical manifestations, affecting multiple organ systems. This report underscores the diagnostic complexities associated with complex clinical presentation and highlights the importance of multidisciplinary collaboration in addressing challenging clinical scenarios, particularly among heavy smoker male patients and intricate radiological presentations.

Pulmonary Langerhans Cell Histiocytosis Post-Hodgkin Lymphoma Completely Resolved With Vinblastine in a Heavy Smoker: Coincidence or Causation?

The association among Langerhans cell histiocytosis, hematolymphoid malignancies, and heavy smoking has been addressed in medical literature to identify a possible potential link. Such occurrence can pose diagnostic challenges, as well as important clinical implications for disease progression and treatment approaches. We present pulmonary Langerhans cell histiocytosis instance in a 35-year-old male patient, with a 34-pack-year smoking history and nodular sclerosing Hodgkin lymphoma stage IIB who developed multiple bilateral lung nodules. The patient completed 6 cycles of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine chemotherapy and radiotherapy 2 years earlier. CT chest scans revealed numerous micronodules scattered randomly throughout the upper and lower left lung lobes. Subsequent wedge resection exhibited cellular proliferation with grooved nuclei, eosinophilic cytoplasm, and surrounding inflammatory components. Immunohistochemical staining showed positive staining for S100 and CD1a confirming a diagnosis of pulmonary Langerhans cell histiocytosis. The patient responded to a 6-week treatment with vinblastine and prednisolone. A subsequent CT scan of the lungs revealed complete resolution after 3 years. This report underscores the importance of identifying pulmonary Langerhans cell histiocytosis in heavy smokers with Hodgkin lymphoma presenting with multiple nodular pulmonary lesions. For patients with Hodgkin lymphoma and a possible genetic predisposition, smoking may contribute to the overt development of pulmonary Langerhans cell histiocytosis. Therefore, smoking cessation and careful follow-up examinations are required. Further research is recommended to elucidate the underlying mechanisms of this intriguing association.

Cutaneous Syncytial Myoepithelioma: An Uncommon and Distinct Variant of Cutaneous Epithelioid Neoplasm.

BACKGROUND: Cutaneous syncytial myoepithelioma (CSM) is an uncommon and distinct variant of cutaneous myoepithelioma. We aim to present a case of CSM to enhance the recognition of this unique variant, encompassing its clinical characteristics, histopathological features, immunohistochemical staining, and therapeutic approaches. CASE PRESENTATION: A 10-year-old girl presented with a dome-shaped nodule located on the skin of her left medial distal arm. Microscopic examination of the skin biopsy revealed a well-defined dermal nodular lesion, surrounded by an epidermal collarette. Tumor cells were composed of epithelioid to spindle-shaped cells with round-to-oval nuclei, small nucleoli, and abundant eosinophilic cytoplasm with a syncytial-like growth pattern. A moderate degree of nuclear pleomorphism was noted. Mitotic activity was not prominent. Immunohistochemical staining revealed positive staining for epithelial membrane antigen, GLUT1, collagen IV, and S100. Smooth muscle actin, CD10, and CD68 showed patchy positivity. CD31, CD34, p63, SOX10, anaplastic lymphoma kinase (ALK), glial fibrillary acidic protein, pankeratin (AE1/AE3/PCK26), Melan-A, and CD1a were negative. Fluorescence in situ hybridization targeting TFE3 and ALK genes was negative. The differential diagnosis included ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, and CSM. Based on the above findings, a diagnosis of CSM was rendered. DISCUSSION: CSM is a benign cutaneous neoplasm composed of sheets of histiocytoid or short spindle cells with pale eosinophilic cytoplasm with a syncytial-like growth pattern. Clinically, CSM often presents as a painless, slow-growing nodule or plaque in a broad anatomical distribution with a preference for the distal extremities. CSM is characteristically positive for epithelial membrane antigen (EMA) and S100 protein and negative for keratins. In challenging cases, molecular testing for EWSR1 gene rearrangement and EWSR1-PBX3 gene fusion aid in confirming the diagnosis. CONCLUSIONS: The histologic features of CSM present a unique set of challenges posing a diagnostic dilemma, as they can bear resemblance to a range of benign and malignant cutaneous neoplasms including ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, malignant or nevoid melanoma, and epithelioid sarcoma. An accurate diagnosis is crucial for guiding proper clinical management considering that this entity typically demonstrates an excellent prognosis following a complete surgical excision.

Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man.

ABSTRACT: Melanoma with lymphatic invasion has been associated with increased risk of metastasis, but the mechanisms and clinical implications are poorly understood. Although current reports have documented angiotropic spread of melanoma and suggest lymphatic spread of melanoma to increase the likelihood of metastasis, to our knowledge, lymphangitic metastatic melanoma resembling cutaneous carcinomatosis or presenting with facial hyperpigmentation has not been described. In this case report, we describe extensive cutaneous intralymphatic spread of melanoma, or lymphangitic melanomatosis, producing macular skin pigmentation in a 66-year-old man.