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.

Cutaneous Atypical Fibroxanthoma With Osteoclast-Like Giant Cell: A Rare but Diagnostic Pitfall.

BACKGROUND: Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. CASE PRESENTATION: A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. CONCLUSION: Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

Immunohistochemical Markers With Potential Diagnostic, Prognostic, and Therapeutic Significance in Uterine Carcinosarcoma: A Clinicopathologic Study of 43 Cases.

Uterine carcinosarcomas (UCS) are rare and highly aggressive tumors. Although it is currently accepted that the majority of UCS are metaplastic carcinomas, their aggressive behavior is unparalleled to that of any other high-grade endometrial neoplasms. Therefore, the search for the distinct immunohistochemical and molecular features that could help in the development of new treatment strategies continues. We evaluated the expression of PDL-1, growth hormone releasing hormone receptor, p53, WT1, PAX-8, estrogen receptor, HNF-1, and mismatch repair proteins in 43 UCS. Tumors were selected from the archives of the Magee-Womens Hospital University of Pittsburgh Medical Center Department of Pathology. Seventeen were stage I, 4 were stage II, 15 were stage III, and 7 were stage IV. The median age was 67 yr and median overall survival was 3.2 yr. Immunostaining for PAX8, HNF-1, and estrogen receptor showed statistically significant difference between epithelial and stromal components. Expression of p53 was significantly associated with clinical high stage, but other markers did not correlate with stage or survival. Immunostaining for programmed death ligand-1 was strongly positive in 30 UCS (70%), including 24 cases with tumor cell positivity, 12 cases with tumor cell and tumor-infiltrating immune cell positivity, and 6 cases with tumor-infiltrating immune cell positivity only. Of 27 tumors tested for mismatch repair expression, 12 (44%) showed loss of expression, 7 of which were PDL-1 positive. Growth hormone releasing hormone receptor was positive in 38 tumors (88%) and predominantly expressed in the epithelial component. The range of positivity for programmed death ligand-1 and growth hormone releasing hormone receptor suggests a possible potential adjuvant treatment that may be considered for UCS.

Cutaneous neoplasms composed of melanoma and carcinoma: A rare but important diagnostic pitfall and review of the literature.

We report two cases of combined cutaneous tumors composed of melanoma and carcinoma. The first tumor presented as a 5-mm pink-blue macule over the right zygomatic arch in an 85-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of melanoma (highlighted by SOX10 and MART-1, with high Ki-67 proliferative index) intermixed with nodular basal cell carcinoma (highlighted by pan-cytokeratin and Ber-EP4). The neoplastic melanocytes were confined to the basal cell carcinoma nodules, and a diagnosis of combined melanoma in situ and basal cell carcinoma was rendered. After therapeutic excision, the patient was disease-free at 9 months after the initial diagnosis. The second tumor presented as a 6-mm pink-brown crusted papule on the right forehead in an 89-year-old man. Shave biopsy and immunohistochemical studies revealed that the tumor was composed of malignant melanoma (MM) (highlighted by S100 and MART-1) intermixed with squamous cell carcinoma (SCC) (highlighted by cytokeratin and p63), and a diagnosis of combined MM-SCC was rendered. These two cases highlight the importance of recognizing these rare types of melanocytic-epithelial cutaneous neoplasms to arrive at an accurate diagnosis that may inform appropriate disease stage and therapy.

Superficial Basal Cell Cancers Demonstrate Higher Rates of Mixed Histology on High-Risk Anatomical Sites.

BACKGROUND: The Mohs Appropriate Use Criteria (MAUC) have come into question recently regarding the most appropriate treatment for superficial basal cell carcinoma (sBCC). At the heart of this debate is the limited body of evidence describing tumor behavior of sBCC based on clinical factors relevant to the MAUC. OBJECTIVE: To determine whether sBCC is more likely to harbor aggressive subtypes in high-risk anatomical locations and in immunocompromised patients. MATERIALS AND METHODS: A single institution retrospective review produced 133 evaluable Mohs cases performed on sBCC over a 10-year period. All slides from the respective cases were reviewed for the presence of histologic patterns other than known sBCC. Cases were then grouped by both MAUC anatomical zone (H, M, and L) and patient immune status for statistical analysis. RESULTS: A significantly higher rate of mixed histology (MH) was observed when comparing Zone H with Zone L across all patients, healthy patients, and immunocompromised patients. The same was true when comparing Zone M with Zone L for all patients and healthy patients (immunocompromised did not reach significance). CONCLUSION: The authors' data very clearly demonstrate a higher rate of MH in sBCC of the head and neck which provides strong support to the current MAUC scoring.

Prevalence and Outcome of Preterm Births in the National Referral Hospital in Bhutan: An Observational Study.

INTRODUCTION: Preterm birth-related complications are the leading cause of under-5 mortality globally. Bhutan does not have a reliable preterm birth rate or data regarding outcome of preterm babies. AIM: To determine the preterm birth rate at the Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu, Bhutan, and assess their outcomes. METHODS: All live preterm births at JDWNRH from 1 January 2017 to 31 December 2017 were followed from birth till hospital discharge. Maternal demographic data, pregnancy details and delivery details were collected. Morbidity and mortality information as well as discharge outcome were collected on babies admitted to neonatal intensive care unit (NICU). RESULTS: Preterm birth rate among live births was 6.4%. Most mothers were younger than 30 years, housewives and had secondary education. Pregnancy registration rate and adequacy of antenatal visits were high. Most preterm births were singleton and the predominant mode of delivery was cesarean section. More than half of the births were initiated spontaneously, and the male:female ratio was 1.2:1. Most babies were late preterm and low birth weight. Half of them required NICU admission. Overall mortality rate was 11% and 21.6% for admitted preterm neonates. Preterm small-for-gestational-age neonates, and those born after provider-initiated preterm birth had significantly increased risk of mortality. Most preterm neonates were discharged without complications. The rate of extrauterine growth restriction was high. CONCLUSION: This is the first study on the prevalence of preterm births and their outcomes in the largest tertiary-care hospital in Bhutan.

Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma.

Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes. Genomic profiles of 25 HGUCs and 25 colorectal adenocarcinomas using next-generation sequencing of 50 genes were compared with primary bladder adenocarcinoma. Genomic profiles were visualized using JavaScript library D3.js. A striking finding was the distinct lack of genomic alterations across the 51 genes assessed in mucinous subtype of primary bladder adenocarcinoma. Eleven of 15 primary bladder adenocarcinoma harbored at least one genomic alteration in TP53, KRAS, PIK3CA, CTNNB1, APC, TERT, FBXW7, IDH2 and RB1, many of which are novel findings and of potential therapeutic significance. CTNNB1 and APC mutations were restricted to enteric subtype only. While genomic alterations of primary bladder adenocarcinoma showed substantial overlap with colorectal adenocarcinoma, FGFR3 and HRAS mutations and APC, CTNNB1 and IDH2 alterations were mutually exclusive between primary bladder adenocarcinoma and high-grade urothelial carcinoma. These alterations affecting the MAP kinase, PI3K/Akt, Wnt, IDH (metabolic) and Tp53/Rb1 signaling pathways may provide the opportunity for defining targeted therapeutic approaches.

Hypopigmented Mycosis Fungoides with Large Cell Transformation in a Child.

Hypopigmented mycosis fungoides (HMF) is the most common variant of mycosis fungoides (MF) in children. Large-cell transformation in HMF has never been reported. Herein we report a case of HMF in an 8-year-old boy who presented with a 6-year history of hypopigmented patches on the bilateral arms, lower back, buttocks, posterior thighs, and lower legs. Biopsy revealed an abnormal CD8+ epidermotropic T-cell infiltrate consistent with the diagnosis of MF. The T-cell clonality study was positive. The patient was started on narrowband ultraviolet B (NBUVB) phototherapy and topical steroids. He had a 50% reduction in his patches after 10 months of treatment, after which he developed a single annular plaque on his left thigh. The biopsy specimen demonstrated large cells that were diffusely CD8+ and CD30- . Clobetasol propionate ointment was prescribed, which led to complete resolution of the plaque within 2 weeks. NBUVB phototherapy was continued and the patient had a complete response within the following 5 months. The case is an example of exceptionally rare large-cell transformation in pediatric MF and stresses the importance of regular follow-up of these patients.

BRCA-mutated Invasive Breast Carcinomas: Immunohistochemical Analysis of Insulin-like Growth Factor II mRNA-binding Protein (IMP3), Cytokeratin 8/18, and Cytokeratin 14.

To evaluate the expression of insulin-like growth factor II mRNA-binding protein (IMP3), CK8/18, and CK14 in BRCA mutated and sporadic invasive breast carcinoma. Immunohistochemistry for IMP3, CK8/18, and CK14 was performed on 39 cases of invasive breast carcinomas with BRCA mutation (24 BRCA1, 14 BRCA2, and 1 dual BRCA1/BRCA2) and 54 cases of sporadic invasive breast carcinomas. The relationship between the IMP3, CK8/18, and CK14 and the tumor grade and molecular phenotypes were analyzed. IMP3, CK8/18, and CK14 positivity were present in 20 (51%), 22 (56%), and 14 (36%) of 39 BRCA-mutated breast carcinomas, and 11 (20%), 53 (98%), and 24 (44%) of 54 sporadic breast carcinomas respectively. The rates of IMP3 expression and absence of CK8/18 (44% versus 2%) in BRCA-mutated breast carcinomas was significantly higher than the sporadic breast carcinomas (p = 0.002 and p < 0.001). No significant difference was observed for CK14 among the two groups (p = 0.408). No significant difference was observed among BRCA1-related and BRCA2-related breast carcinomas in the immunoprofile for IMP3, CK8/18, and CK14. No significant correlation was identified between the expression of IMP3 and CK8/18 and the tumor grade in both BRCA-mutated and sporadic breast carcinomas (p > 0.05). In cases with luminal A and B phenotypes, the rates of expression of IMP3 and loss of CK8/18 were significantly higher in BRCA-mutated as compared to sporadic breast carcinoma (p < 0.001). In cases with basal-like phenotype, the absence of CK8/18 expression was significantly higher in BRCA-mutated breast carcinomas (54% versus 0%, p = 0.001), while no difference was observed for IMP3 expression (p = 0.435). Regardless of mutation type, histologic grade, or molecular phenotype, the absence of CK8/18 expression and presence of IMP3 expression are seen at much higher rate in BRCA mutated breast carcinomas.

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.

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.

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.

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.