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.

Cytopathology in the era of social media.

In today's medical landscape, social media (SoMe) platforms have expanded their reach beyond mere communication and entertainment, making a significant impact in the pathology field, including cytopathology. In recent years, SoMe platforms have become increasingly adopted by cytopathologists, facilitating continued education, professional networking, enhancing patient engagement, and entertainment. This adoption has influenced the professional growth of cytopathologists, and at its best, has led to the establishment of a robust professional online presence and ultimately contributed to leadership positions, fellowship opportunities, and academic promotions. Moreover, the integration of SoMe into the academic field has shown a profound impact on the visibility of academic journals and has provided a platform for lower-impact factor journals to expand their reach, ultimately increasing article citation rates and positively contributing to journal impact factor growth. SoMe platforms created a modern avenue for conference networking that has revolutionized knowledge dissemination and enhanced real-time engagement. The advantages of SoMe have extended to a global scale, positively enhancing professional expertise sharing, facilitating effective communication and teleconsultation worldwide, and reaching developing countries. Drawing insights from the recent medical literature and the practical insight from the experts' personal experience, this article provides a comprehensive review of how SoMe and cytopathology intersect to create new opportunities, facilitating informed discussions, global collaboration, and advancements in the field of cytopathology. This article also delves into the challenges surrounding SoMe platform navigation and addresses ethical and regulatory concerns, providing guidelines on what to post and what not to post on SoMe platforms.

Anti-cytokine Storm Activity of Fraxin, Quercetin, and their Combination on Lipopolysaccharide-Induced Cytokine Storm in Mice: Implications in COVID-19.

Background: Cytokine release syndrome (CRS) is the leading cause of mortality in advanced stages of coronavirus patients. This study examined the prophylactic effects of fraxin, quercetin, and a combination of fraxin+quercetin (FQ) on lipopolysaccharide-induced mice. Methods: Sixty mice were divided into six groups (n=10) as follows: control, LPS only, fraxin (120 mg/Kg), quercetin (100 mg/Kg), dexamethasone (5 mg/Kg), and FQ. All treatments were administered intraperitoneally (IP) one hour before induction by LPS (5 mg/Kg) IP injection. Twenty-four hours later, the mice were euthanized. Interleukin one beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA), and lung and kidney tissues were examined for histopathological alterations. This study was conducted at Al-Nahrain University, Baghdad, Iraq, in 2022. Results: FQ reduced IL-1ß (P<0.001). All treatments significantly suppressed IL-6, fraxin, quercetin, dexamethasone, and FQ, all with P<0.001. The TNF-α level was reduced more with dexamethasone (P<0.001) and quercetin (P<0.001). Histopathological scores were significantly reduced mainly by quercetin and FQ in the lungs with scores of 12.30±0.20 (P=0.093), and 15.70±0.20 (P=0.531), respectively. The scores were 13±0.26 (P=0.074) and 15±0.26 (P=0.222) for quercetin and FQ in the kidneys, respectively. Conclusion: All used treatments reduced proinflammatory cytokine levels and protected against LPS-induced tissue damage.

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.

Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-ß1/Smad2/3 pathways.

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-ß1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.

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.

Erythema Multiforme-Like Fixed Drug Eruption During Azathioprine and Hydroxychloroquine Treatment for Systemic Lupus Erythematosus Mimicking Rowell Syndrome: A Rare and Challenging Clinical Scenario.

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing.

Automated imaging analysis of Ki-67 immunohistochemistry on whole slide images of cell blocks from pancreatic neuroendocrine neoplasms.

INTRODUCTION: Accurate grading of pancreatic neuroendocrine tumors (PanNETs) relies on the assessment of Ki-67 immunohistochemistry (IHC). While digital imaging analysis (DIA) has been employed for Ki-67 IHC assessment in surgical specimens, its applicability to cytologic specimens remains underexplored. This study aimed to evaluate an automated DIA for assessing Ki-67 IHC on PanNET cell blocks. MATERIALS AND METHODS: The study included 61 consecutive PanNETs and 5 pancreatic neuroendocrine carcinomas. Ki-67 IHC slides from cell blocks were digitally scanned into whole slide images using Philips IntelliSite Scanners and analyzed in batches using the Visiopharm Ki-67 App in a digital workflow. Ki-67 scores obtained through DIA were compared to pathologists' manual scores. RESULTS: The Pearson correlation coefficient of the percentage of Ki-67-stained nuclei between DIA reads and the originally reported reads was 0.9681. Concordance between DIA Ki-67 grades and pathologists' Ki-67 grades was observed in 92.4% (61/66) of cases with the calculated Cohen's Kappa coefficient of 0.862 (almost perfect agreement). Discordance between DIA and pathologists' consensus reads occurred in 5 PanNET cases which were upgraded from G1 to G2 by DIA due to contaminated Ki-67-stained inflammatory cells. CONCLUSIONS: DIA demonstrated excellent concordance with pathologists' assessments, with only minor grading discrepancies. However, the essential role of pathologists in confirming results is emphasized to enhance overall accuracy.

Myxoid neurofibroma masquerading as lymphatic-venous malformation and poses a diagnostic challenge on fine needle aspiration biopsy.

BACKGROUND: Myxoid neurofibromas (NF) are uncommon, benign spindle cell tumors that originate from peripheral nerve sheaths, often posing a diagnostic challenge due to their hypocellularity on cytology specimens. Distinguishing myxoid spindle cell lesions can be challenging, given the broad range of potential differential diagnoses. CASE PRESENTATION: A 26-year-old female with a past medical history of embolized inguinal, flank, and retroperitoneal venolymphatic malformation presented with a left pelvic pain causing significant disability. CT scan showed an extensive 8.7 cm × 6.6 cm retroperitoneal mass. FNA was performed and alcohol-fixed papanicolaou-stained smears showed a hypocellular specimen with loosely arranged clusters of bland spindle cell proliferation in the background of a mucoid matrix. Spindle cells showed scant cytoplasm and elongated oval-shaped regular nuclei. Prominent nucleoli were not seen. An excisional biopsy revealed a bland spindle cell proliferation in a myxoid background associated with shredded collagen bundles. Immunohistochemical staining showed diffuse positivity for S100 and CD34. Based on the overall findings, a definitive diagnosis of myxoid neurofibroma was rendered. DISCUSSION: Cytological features of myxoid neurofibroma include the presence of hypocellular spindle-shaped cells arranged in small, loosely organized groups within a myxoid matrix background. Cells exhibit scant cytoplasm with regular oval and elongated nuclei. Nucleoli are typically not identified. The differential diagnosis includes myxoid neurofibroma, myxoma, myxoid liposarcoma, myxoid chondrosarcoma, myxoid dermatofibrosarcoma protuberans, low-grade fibromyxoid sarcoma, and low-grade myxo-fibrosarcoma. CONCLUSION: We aim to highlight the importance of considering myxoid neurofibroma in the differential diagnosis of hypocellular myxoid spindle cell lesions encountered on fine-needle aspiration cytology.

Lipoprotein Glomerulopathy With Complete Resolution With Fenofibrate: Report of First Case From Pakistan.

Background: Lipoprotein glomerulopathy is an infrequent glomerular disorder that culminates in nephrotic syndrome and often progresses to kidney failure. Whereas most patients have been reported in Japan and China, limited reports have been documented outside these regions. This patient represents the first report of lipoprotein glomerulopathy in Pakistan. Case Presentation: A 25-year-old male patient, hypertensive for 2 years, presented with progressive body edema, frothy urine, and fatigue. Examination revealed elevated blood pressure, bilateral pedal edema, and positive shifting dullness. Laboratory results showed significant proteinuria and elevated cholesterol and triglyceride levels. Renal biopsy revealed enlarged glomeruli with a dilated capillary lumen filled with pale-staining mesh-like material "lipoprotein thrombi." Mild tubular atrophy and interstitial inflammation were observed. No interstitial fibrosis was evident. Electron microscopy detailed the lipoprotein thrombi with lipid granules and vacuoles of various sizes. A diagnosis of lipoprotein glomerulopathy was rendered. Treatment with fenofibrate, rosuvastatin, and captopril led to notable improvements in symptoms, blood pressure, and lipid levels during a 6-month follow-up. Subsequent biopsy showed complete resolution of the lipoprotein thrombi and a significant reduction in subendothelial granular densities. However, the flocculent subendothelial material persisted to some extent despite the complete resolution of lipoprotein thrombi. Conclusion: This report underscores the rarity of lipoprotein glomerulopathy in Pakistan and contributes valuable insights into its histopathologic features and global epidemiology. This unique instance aims to raise awareness among healthcare professionals, aiding in improved recognition of this rare entity. The favorable response to fenofibrate treatment underscores its effectiveness in managing lipoprotein glomerulopathy.

Malignant Para-Testicular Mesothelioma: A Rare Presentation in the Tunica Vaginalis of an Elderly Male With No Prior Asbestos Exposure.

Malignant mesothelioma of the tunica vaginalis is an extremely rare and aggressive tumor that is frequently encountered in elderly patients. The diagnosis of malignant mesothelioma of the tunica vaginalis poses a diagnostic challenge due to its infrequency and nonspecific clinical presentation. Histopathological examination and immunohistochemical staining are essential in differentiating this tumor from other para-testicular masses and establishing a definitive diagnosis. Early detection and comprehensive treatment planning are crucial for improving the prognosis and overall outcomes for patients with this rare malignancy. We present a report of malignant mesothelioma of the tunica vaginalis in a 78-year-old male patient with no history of asbestos exposure who presented with a large infiltrative left para-testicular mass. Histopathological examination revealed a biphasic proliferation composed of epithelioid and spindle cells with infiltrative features, foci of necrosis, and increased mitotic figures. Immunohistochemical staining exhibited positive staining for WT1, D2-40, and calretinin, supporting the mesothelial origin of the tumor. Notably, BerEP4 staining was negative, arguing against carcinoma. Immunostaining for keratin 5 was positive, supporting the mesothelial differentiation. The Ki67 proliferation index was high. The differential diagnosis included adenomatoid tumors, germ cell tumors, and pleomorphic sarcoma. We aim to discuss the clinical presentation, diagnostic approach, and therapeutic approaches of this rare entity.

Extra-Ocular Sebaceous Carcinoma in Situ of the Arm of an Elder Male: An Unusual Presentation in an Atypical Location.

Background. Sebaceous carcinoma in situ outside the ocular region is an exceedingly uncommon. It is an intraepidermal neoplasm originating from sebaceous glands limited to the epidermis with no invasion into the underlying dermis or beyond. Although sebaceous carcinoma in situ is predominantly observed in ocular regions, particularly the eyelids, instances of its occurrence in extraocular locations are infrequent, with only a limited number of examples reported in the literature. Case Presentation. A 63-year-old man presented with a left posterior arm lesion. Microscopic examination revealed a proliferation of poorly differentiated atypical neoplastic sebocytes confined to the epidermis with pleomorphic nuclei, prominent nucleoli, and clear cell changes. The neoplastic cells demonstrated positive staining for adipophilin, androgen receptor, epithelial membrane antigen, P63, BerEP4, and keratin 7. Microsatellite instability markers showed preserved nuclear staining for MLH1, PMS2, MSH2, and MSH6. A definitive diagnosis of sebaceous carcinoma in situ was rendered. Discussion. The distinctive histopathologic characteristics typically involve the presence of atypical sebaceous cells confined within the epidermis. Atypical cells often exhibit enlarged nuclei, increased mitotic activity, and prominent nucleoli. A panel of epithelial membrane antigen, adipophilin, and androgen receptors is essential for ensuring an accurate diagnosis. Conclusion. This report underscores the importance of considering sebaceous carcinoma in situ in diagnosis in atypical locations, emphasizing the need for a comprehensive histopathologic examination and immunohistochemical staining panel. This article aims to demonstrate the rarity of sebaceous carcinoma in situ in extraocular sites to broaden our understanding of its diverse clinical presentations.

Pulmonary Histoplasmosis Complicated by Nonvalvular Right Ventricular Wall Histoplasma capsulatum Endocarditis.

Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is uncommon. In this report, we provide a detailed description of severe pulmonary histoplasmosis complicated by the disease involvement of the free wall of the right ventricle. A 55-year-old female presented with cough, fevers, dyspnea, and 30-pound unintentional weight loss in 6 months. Her past medical history was significant for supraventricular tachycardia with permanent pacemaker implantation. Imaging studies revealed an intracardiac mass accompanied by mediastinal lymphadenopathy and bilateral lung nodules. Endobronchial ultrasound-guided transbronchial needle aspiration of station 4R lymph nodes revealed numerous yeast forms, morphologically consistent with Histoplasma capsulatum. The diagnosis was further corroborated by the elevated titers of serum antibodies against Histoplasma capsulatum. The right ventricular mass debulking with biopsy showed necrotizing granulomatous inflammation involving nonvalvular endocardium and myocardium of the free wall of the right ventricle. The report documents an unusual presentation of pulmonary histoplasmosis accompanied by nonvalvular endocarditis and suggests a possible association between the site of the cardiac infection and the presence of a permanent intravascular pacer device.