Pub Date : 2024-04-23DOI: 10.1097/dad.0000000000002718
Anne Lynn S Chang, Ryanne Brown, Shufeng Li, Nicolas Betancourt, Joyce Teng
Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.
{"title":"Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.","authors":"Anne Lynn S Chang, Ryanne Brown, Shufeng Li, Nicolas Betancourt, Joyce Teng","doi":"10.1097/dad.0000000000002718","DOIUrl":"https://doi.org/10.1097/dad.0000000000002718","url":null,"abstract":"Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1097/dad.0000000000002719
Badr AbdullGaffar, T. Keloth
Rhabdomyomatous mesenchymal hamartoma (RMH) typically presents as a congenital midline head and neck cutaneous polyp in infants. Perianal and mucocutaneous lesions have been reported, and recently, acquired adult-onset variants have been proposed. This makes the true prevalence, etiopathogenesis, and clinicopathologic distribution and classification of RMHs in children compared with those in adults uncertain. We performed a retrospective review to highlight the salient histopathologic, histochemical, and immunohistochemical features in RMHs and to emphasize their specific clinicopathologic criteria to avoid diagnostic pitfalls. We found 4 (0.3%) infants [2 female infants and 2 male infants, average age: 4 months] with mental, nasal, lingual, and perianal midline RMHs (average size: 1.0 cm) of 1303 patients with cutaneous polypoid lesions. Three were isolated, and 1 was associated with Goldenhar syndrome. The cutaneous polyps demonstrated intermixed skeletal muscle, adipose, and fibrocollagenous core stroma that extended into the dermis and around the dermal appendages. The lingual lesion demonstrated skeletal muscle and fibrocollagenous stroma with prominent nerve bundles and little adipose tissue. All showed interstitial loose mesenchyme. Masson trichome demarcated the triphasic stromal components. Alcian blue demonstrated the loose myxoid mesenchyme. Elastic van Gieson did not show elastic fibers. Desmin demonstrated the skeletal muscle bundles, S100 highlighted the adipose tissue lobules and the nerve bundles, and CD34 displayed the mesenchymal stroma. Ki67 showed a low proliferation index in the loose mesenchyme. Smooth muscle actin did not reveal smooth muscle bundles, but with CD31, they highlighted the thick blood vessels. CD117 revealed prominent mast cells. From our retrospective review series, 4 cases that originally diagnosed as RMHs were excluded. Likewise, we found some examples of the reported cases in the English literature that might have been mistaken for RMHs. This is because they did not fulfill the diagnostic clinicopathologic criteria. RMH constitutes a rare entity with specific clinicopathologic features. Most lesions are isolated. Some are associated with congenital anomalies and syndromes. Strict clinicopathologic diagnostic criteria should be applied to avoid mislabeling look-alike lesions for RMHs.
{"title":"Rhabdomyomatous Mesenchymal Hamartoma: Report of 4 Cases With Histochemical and Immunohistochemical Findings and Emphasis on Potential Pitfalls","authors":"Badr AbdullGaffar, T. Keloth","doi":"10.1097/dad.0000000000002719","DOIUrl":"https://doi.org/10.1097/dad.0000000000002719","url":null,"abstract":"\u0000 Rhabdomyomatous mesenchymal hamartoma (RMH) typically presents as a congenital midline head and neck cutaneous polyp in infants. Perianal and mucocutaneous lesions have been reported, and recently, acquired adult-onset variants have been proposed. This makes the true prevalence, etiopathogenesis, and clinicopathologic distribution and classification of RMHs in children compared with those in adults uncertain. We performed a retrospective review to highlight the salient histopathologic, histochemical, and immunohistochemical features in RMHs and to emphasize their specific clinicopathologic criteria to avoid diagnostic pitfalls. We found 4 (0.3%) infants [2 female infants and 2 male infants, average age: 4 months] with mental, nasal, lingual, and perianal midline RMHs (average size: 1.0 cm) of 1303 patients with cutaneous polypoid lesions. Three were isolated, and 1 was associated with Goldenhar syndrome. The cutaneous polyps demonstrated intermixed skeletal muscle, adipose, and fibrocollagenous core stroma that extended into the dermis and around the dermal appendages. The lingual lesion demonstrated skeletal muscle and fibrocollagenous stroma with prominent nerve bundles and little adipose tissue. All showed interstitial loose mesenchyme. Masson trichome demarcated the triphasic stromal components. Alcian blue demonstrated the loose myxoid mesenchyme. Elastic van Gieson did not show elastic fibers. Desmin demonstrated the skeletal muscle bundles, S100 highlighted the adipose tissue lobules and the nerve bundles, and CD34 displayed the mesenchymal stroma. Ki67 showed a low proliferation index in the loose mesenchyme. Smooth muscle actin did not reveal smooth muscle bundles, but with CD31, they highlighted the thick blood vessels. CD117 revealed prominent mast cells. From our retrospective review series, 4 cases that originally diagnosed as RMHs were excluded. Likewise, we found some examples of the reported cases in the English literature that might have been mistaken for RMHs. This is because they did not fulfill the diagnostic clinicopathologic criteria. RMH constitutes a rare entity with specific clinicopathologic features. Most lesions are isolated. Some are associated with congenital anomalies and syndromes. Strict clinicopathologic diagnostic criteria should be applied to avoid mislabeling look-alike lesions for RMHs.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140670157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Information regarding the genetic alterations in extramammary Paget disease (EMPD) is scarce. This study investigated the significance of CDKN2A and MTAP alterations in EMPD progression using immunohistochemistry and panel DNA sequencing. In total, 24 invasive/metastatic EMPD cases were included in this study. The immunoexpression of p16 and MTAP in the primary in situ, primary invasive, and metastatic tumor components was evaluated. Panel DNA sequencing was performed for metastatic tumor components in 5 of the 24 cases. Immunoexpression of p16 in the in situ tumor component was at least partially preserved in all 19 tested cases (100%). By contrast, the invasive tumor component was diffusely or partially lost in 18 (81.8%) of 22 tested cases. Regarding the foci of lymph node metastasis, 13 (81.2%) of the 16 patients showed a significant loss of p16 expression. Loss of MTAP immunoexpression was observed less frequently compared with the loss of p16 expression. CDKN2A homozygous deletions were confirmed in all 5 tested cases by sequencing, whereas MTAP deletions were detected in only 2 cases. In conclusion, p16 expression loss and CDKN2A deletions can be frequently seen in invasive/metastatic cases of EMPD.
{"title":"Loss of p16 Immunoexpression and Deletions of CDKN2A in the Progression of Extramammary Paget Disease: An Immunohistochemical and Genetic Study of 24 Invasive/Metastatic Cases.","authors":"Tsubasa Hiraki, Takuma Oishi, Shusuke Yoshikawa, Keiichiro Honma, Shuichi Ohe, Taiki Isei, Yoji Kukita, Toshihiro Takai, Keiji Shimada, Yusuke Takei, Keisuke Goto","doi":"10.1097/dad.0000000000002726","DOIUrl":"https://doi.org/10.1097/dad.0000000000002726","url":null,"abstract":"Information regarding the genetic alterations in extramammary Paget disease (EMPD) is scarce. This study investigated the significance of CDKN2A and MTAP alterations in EMPD progression using immunohistochemistry and panel DNA sequencing. In total, 24 invasive/metastatic EMPD cases were included in this study. The immunoexpression of p16 and MTAP in the primary in situ, primary invasive, and metastatic tumor components was evaluated. Panel DNA sequencing was performed for metastatic tumor components in 5 of the 24 cases. Immunoexpression of p16 in the in situ tumor component was at least partially preserved in all 19 tested cases (100%). By contrast, the invasive tumor component was diffusely or partially lost in 18 (81.8%) of 22 tested cases. Regarding the foci of lymph node metastasis, 13 (81.2%) of the 16 patients showed a significant loss of p16 expression. Loss of MTAP immunoexpression was observed less frequently compared with the loss of p16 expression. CDKN2A homozygous deletions were confirmed in all 5 tested cases by sequencing, whereas MTAP deletions were detected in only 2 cases. In conclusion, p16 expression loss and CDKN2A deletions can be frequently seen in invasive/metastatic cases of EMPD.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1097/dad.0000000000002712
Advaita S Chaudhari, Jason R McFadden, Jessica Bentz, Rebecca H Evans, Maria A Selim, Aravindhan Sriharan
Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she "does not always remember to apply" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.
分化型外阴上皮内瘤变（d-VIN）是一种与 HPV 无关的外阴鳞状细胞癌的前驱病变。d-VIN病变的组织学很难与非肿瘤性上皮病变，尤其是硬皮病（LS）区分开来。作者介绍了一例 LS 病例，仅依靠组织病理学可能会导致误诊。患者是一名 17 岁的女性，临床特征为外阴皮炎和 LS，已有两年之久。医生建议她每天在患处涂抹0.05%的氯倍他索，但6个月后仍不见好转。右侧大阴唇的活组织检查发现了典型的 d-VIN 组织学特征和近乎连续的 p53 表达。这些特征是 d-VIN 的特征。然而，d-VIN 在年轻患者中极为罕见。6 位皮肤病理学家和妇科病理学家对该病例进行了审查，他们认为炎症的程度在氯倍他索治疗后并不常见，可能是由于患者未遵医嘱所致。查看患者病历后发现，她 "并不总是记得使用 "氯倍他索。患者的临床医生证实她存在依从性问题，随访活检结果显示 d-VIN 阴性。该病例被签出为 LS 病例，并附注说明了上述情况，如果仍有疑虑，将重新活检。作者推测，活检区域的炎症浸润导致反应性非典型性，原因是患者没有坚持治疗。虽然患者的年龄有助于排除 d-VIN 的可能性，但老年患者中也可能出现类似病例。病理学家必须意识到，未经治疗的反应性 LS 可模拟 d-VIN，以避免误诊。
{"title":"A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy.","authors":"Advaita S Chaudhari, Jason R McFadden, Jessica Bentz, Rebecca H Evans, Maria A Selim, Aravindhan Sriharan","doi":"10.1097/dad.0000000000002712","DOIUrl":"https://doi.org/10.1097/dad.0000000000002712","url":null,"abstract":"Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she \"does not always remember to apply\" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1097/dad.0000000000002648
Serra Kayaçetin, Devrim Tuba Öcalan, Ülker Gül
The aim of this study was to investigate whether the histopathological findings of psoriasis varied by the biopsied lesion location. Age, gender, age at disease onset, lesion locations, presence or absence of a preliminary diagnosis of psoriasis, and histopathological findings of 307 patients were recorded. The sections prepared from the patients' paraffin blocks were reexamined microscopically, the severity of the observed findings was graded, and various histopathological features were recorded. The female-to-male ratio was 1.2 to 1. Family history for psoriasis was positive in 30% of patients. A clinically preliminary diagnosis of psoriasis was present in 232 patients. The most common histopathological features included hyperkeratosis, parakeratosis, Munro/Kogoj microabscesses, suprapapillary thinning-hypogranulosis, and vascular dilation-capillary proliferation. Hyperkeratosis was least common in the trunk. A linear and moderately strong correlation was found between the histopathological findings of inflammation, capillary proliferation, and suprapapillary thinning. For the first time, the clinical and demographic features of psoriasis are evaluated and the severity of the histopathological findings is compared by the biopsied lesion location in a large number of patients.
{"title":"Comparison of Histopathological Findings in Psoriasis According to the Lesion Location From Biopsy.","authors":"Serra Kayaçetin, Devrim Tuba Öcalan, Ülker Gül","doi":"10.1097/dad.0000000000002648","DOIUrl":"https://doi.org/10.1097/dad.0000000000002648","url":null,"abstract":"The aim of this study was to investigate whether the histopathological findings of psoriasis varied by the biopsied lesion location. Age, gender, age at disease onset, lesion locations, presence or absence of a preliminary diagnosis of psoriasis, and histopathological findings of 307 patients were recorded. The sections prepared from the patients' paraffin blocks were reexamined microscopically, the severity of the observed findings was graded, and various histopathological features were recorded. The female-to-male ratio was 1.2 to 1. Family history for psoriasis was positive in 30% of patients. A clinically preliminary diagnosis of psoriasis was present in 232 patients. The most common histopathological features included hyperkeratosis, parakeratosis, Munro/Kogoj microabscesses, suprapapillary thinning-hypogranulosis, and vascular dilation-capillary proliferation. Hyperkeratosis was least common in the trunk. A linear and moderately strong correlation was found between the histopathological findings of inflammation, capillary proliferation, and suprapapillary thinning. For the first time, the clinical and demographic features of psoriasis are evaluated and the severity of the histopathological findings is compared by the biopsied lesion location in a large number of patients.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1097/dad.0000000000002696
Shantanu Srivatsa, Collin-Jamal Smith, Omar P Sangüeza, Jayson Miedema, Frances A Collichio, Paul B Googe
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.
{"title":"Lymphangitic Melanomatosis: Case Report of Intralymphatic Spread of Melanoma in a 66-year-old Man.","authors":"Shantanu Srivatsa, Collin-Jamal Smith, Omar P Sangüeza, Jayson Miedema, Frances A Collichio, Paul B Googe","doi":"10.1097/dad.0000000000002696","DOIUrl":"https://doi.org/10.1097/dad.0000000000002696","url":null,"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.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1097/dad.0000000000002691
Nada Shaker, Robert Phelps, George Niedt, Omar P Sangueza, Julie Youngs, Scott Lauer, Dinesh Pradhan
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.
{"title":"Cutaneous Syncytial Myoepithelioma: An Uncommon and Distinct Variant of Cutaneous Epithelioid Neoplasm.","authors":"Nada Shaker, Robert Phelps, George Niedt, Omar P Sangueza, Julie Youngs, Scott Lauer, Dinesh Pradhan","doi":"10.1097/dad.0000000000002691","DOIUrl":"https://doi.org/10.1097/dad.0000000000002691","url":null,"abstract":"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.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1097/dad.0000000000002697
Filipa Galante Pereira, Gonçalo Esteves, Joaninha Costa Rosa, José Cabeçadas, Mariana Cravo, Maria Inês Matos Silva Barbosa Pereira, Alistair Robson
Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.
肉芽肿性皮肤松弛症（GSS）是真菌病的一种罕见亚型，很少有病例会扩散到血液、淋巴结或内脏。我们介绍了一例早期扩散到肺部的病例。一名 27 岁的女性患者之前身体健康，出现散在的播散性鳞屑斑块，伴有外阴和臀部间坚实肿胀和腹股沟皮肤压痕，病程长达 1 年。她还报告了轻度疲劳和中度劳累时呼吸困难的症状。患者接受了血液化验、皮肤活检和计算机断层扫描。皮肤活检显示，真皮层/表皮层有轻度非典型 T 细胞淋巴细胞浸润，局灶性表皮增生，伴有肉芽肿浸润和弹性吞噬细胞增多。计算机断层扫描显示双侧肺部结节性不透明，呈磨玻璃状。正电子发射断层扫描显示，臀部周围皮肤和皮下、腹股沟和纵隔淋巴结以及肺部信号增强。肺部活检证实有密集的 T 细胞浸润，并伴有大量多核巨细胞。随后，活检还发现食管受累。分子分析表明，皮肤和肺部存在相同的 T 细胞克隆。经过 6 个周期的化疗/局部体外放疗后，患者皮肤出现部分反应，肺部疾病稳定。根据临床/组织学/分子研究结果，在考虑了肉芽肿性真菌病和外周T细胞淋巴瘤（未另作说明）后，首选诊断为伴有全身扩散的GSS。该病例凸显了将 GSS 与炎性肉芽肿性皮炎区分开来的诊断难度。肺部和食管受累在 GSS 中并不多见，同时出现特征性皮肤 GSS 和全身性疾病也给分类带来了额外的挑战。
{"title":"Granulomatous Slack Skin With Lung and Esophagus Involvement: A Case Report and Molecular Analysis.","authors":"Filipa Galante Pereira, Gonçalo Esteves, Joaninha Costa Rosa, José Cabeçadas, Mariana Cravo, Maria Inês Matos Silva Barbosa Pereira, Alistair Robson","doi":"10.1097/dad.0000000000002697","DOIUrl":"https://doi.org/10.1097/dad.0000000000002697","url":null,"abstract":"Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides, and few cases have been known to spread to the blood, lymph nodes, or viscera. We present a case with early dissemination to the lung. A 27-year-old woman, previously healthy, presented with scattered disseminated scaly patches, associated with vulvar and intergluteal firm swelling and groin-skin induration for 1 year. She also reported mild fatigue and breathlessness on moderate exertion. The patient underwent blood tests, skin biopsies, and computed tomography scan. The skin biopsy showed a mildly atypical T-cell lymphoid infiltrate involving the dermis/hypodermis, with focal epidermotropism, associated with a granulomatous infiltrate and elastophagocytosis. The computed tomography scan revealed bilateral ground-glass lung nodular opacities. Positron emission tomography showed an increased signal in the skin and subcutis around the buttocks, inguinal and mediastinal lymph nodes, and lungs. The lung biopsy confirmed a dense T-cell infiltrate with numerous multinucleated giant cells. Subsequently, esophageal involvement was also observed following biopsy. Molecular analyses demonstrated identical T-cell clones in the skin and lung. After 6 cycles of chemotherapy/localized external radiotherapy, the patient had a partial skin response and stable lung disease. A preferred diagnosis of GSS with systemic spread was made based on clinical/histologic/molecular findings, after considering granulomatous mycosis fungoides and peripheral T-cell lymphoma, not otherwise specified. This case highlights the frequent diagnostic difficulty in distinguishing GSS from an inflammatory granulomatous dermatitis. Pulmonary and esophageal involvements are rare in GSS, and the simultaneous presentation of characteristic cutaneous GSS with systemic disease poses an additional classification challenge.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1097/dad.0000000000002681
Jesús I Martínez-Ortega, Grisell Ortega-Valerio, Arely G Ramirez-Cibrian
This report demonstrates the rare variant of bullous pilomatrixoma in a 10-year-old boy who presented with a rapidly growing, red-colored, bullous nodule on his neck after trauma. The exact etiology of this subtype of pilomatrixoma is unclear, but previous studies have suggested that mechanical trauma may trigger its development.
{"title":"Post-traumatic Bullous Pilomatrixoma Exploring the Pathogenesis.","authors":"Jesús I Martínez-Ortega, Grisell Ortega-Valerio, Arely G Ramirez-Cibrian","doi":"10.1097/dad.0000000000002681","DOIUrl":"https://doi.org/10.1097/dad.0000000000002681","url":null,"abstract":"This report demonstrates the rare variant of bullous pilomatrixoma in a 10-year-old boy who presented with a rapidly growing, red-colored, bullous nodule on his neck after trauma. The exact etiology of this subtype of pilomatrixoma is unclear, but previous studies have suggested that mechanical trauma may trigger its development.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-04DOI: 10.1097/dad.0000000000002657
Adithya Christopher Godfred, Zachariah Thomas, Dincy Peter, Anjana Joseph, Lavanya Ravichandran, Anu Anna George, Susanne A Pulimood, Pranay Gaikwad, Ramesh Babu, Meera Thomas, Nihal Thomas, Aaron Chapla
Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.
疣状表皮增生症（EV）是一种罕见的常染色体隐性遗传性皮肤病，由 EVER1 和 EVER2 基因突变引起。此前尚未研究过印度 EV 患者的遗传特征。本报告描述了一个 EV 患者家族的临床表现和分子分析。利用两名受影响的疑似患者和健康对照组（另外两名兄弟姐妹）的基因组 DNA，使用设计用于扩增 EVER1 和 EVER2 基因编码区和剪接位点区的新型引物组进行了常规聚合酶链反应（PCR）。结果表明，在使用针对两个受试者 EVER1 基因第 16 至 18 号外显子的引物组时，均未扩增出任何结果。随后，跨越 15-20 号外显子长度的长程 PCR 和下一代测序显示，EVER1 基因存在 2078 bp 的同源缺失（EVER1:c.2072_2278del）。对该家族进行筛查后发现，另外两个受影响的兄弟姐妹也存在相同的同源缺失（与索引病例相似）。父母和两个无症状的兄弟姐妹是该缺失的杂合子携带者，而一个健康的兄弟姐妹则是阴性。桑格测序验证了这些结果。EVER1 基因第 17 和第 18 号外显子的缺失导致了帧移位，随后过早终止，造成了严重的表型。该基因大缺失的鉴定和验证分别采用了基于逐步扩增片段的目标富集和长程 PCR 方法。在这个家族中，这种简单的策略大大提高了遗传咨询以及早期遗传诊断和筛查的效率。然而，要描述和验证印度 EV 患者的遗传多样性，还需要功能测试和更大规模的研究。
{"title":"A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India.","authors":"Adithya Christopher Godfred, Zachariah Thomas, Dincy Peter, Anjana Joseph, Lavanya Ravichandran, Anu Anna George, Susanne A Pulimood, Pranay Gaikwad, Ramesh Babu, Meera Thomas, Nihal Thomas, Aaron Chapla","doi":"10.1097/dad.0000000000002657","DOIUrl":"https://doi.org/10.1097/dad.0000000000002657","url":null,"abstract":"Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.","PeriodicalId":501833,"journal":{"name":"The American Journal of Dermatopathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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