American Journal of Dermatopathology最新文献

Abstract: Melanoma is a clinically and genetically heterogeneous malignancy that can recur long after initial treatment. We report the case of a 70-year-old man who presented with metastatic cutaneous melanoma 36 years after the initial diagnosis. Initially diagnosed with nodular melanoma on the left heel at age 34 years, the patient experienced metastatic spread to the left groin lymph nodes by age 36 years, followed by various systemic therapies, including interferon and cytokine therapy, and subsequent observation, over 15 years. Two years before his current presentation, the patient noted a growing mass in his right thigh and an enlarged left inguinal lymph node. Fine-needle aspiration biopsy of the lymph node confirmed the recurrence of melanoma. He subsequently underwent inguinofemoral lymph node dissection and resection of the right thigh mass. Histopathological evaluation revealed melanoma characterized by tumorigenic proliferation of pleomorphic epithelioid and spindle cells with abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, sparse lymphocyte infiltration, and minimal necrosis, consistent with an initial diagnosis of Spitzoid melanoma. Genetic profiling using targeted next-generation sequencing identified a novel TMEM106B::BRAF fusion, along with CHEK2 and MUTYH mutations. The BRAF fusion supports the diagnosis of Spitz melanoma, a genetically defined subset of Spitzoid melanoma. This case represents the first report of a TMEM106B::BRAF fusion in melanoma, emphasizing the critical role of molecular profiling in diagnosing and managing this malignancy, and suggesting a potential avenue for future therapeutic exploration.

Abstract: Cutaneous myxomas are extremely rare in the pediatric population. We describe a case of an eyelid cutaneous myxoma with multiple recurrences in an 8-year-old child. The lesion once previously diagnosed as eccrine hidrocystoma had been excised three times with subsequent recurrence. Frozen section diagnosis performed during the fourth excision showed striking basaloid features, prompting deferral of definitive diagnosis to permanent sections. Following routine processing, basaloid proliferations were again seen without significant atypia or mitotic activity in addition to background features of myxoma. CD10 immunostain highlighted both basaloid nests and surrounding stroma. Cutaneous myxoma was diagnosed. The diagnosis was corroborated by an external consultation. The patient underwent genetic testing for the Carney complex with negative results. This case report raises some practical points. First, due to their rarity in the pediatric population and potential to mimic other entities, cutaneous myxomas can be misdiagnosed as other benign neoplasms. Second, although induction of basaloid proliferation has been well-documented in myxoma, it can be easily misinterpreted as a malignant process, particularly in the setting of a frozen section diagnosis and lack of available clinical information. Third, even though solitary cutaneous myxomas are less likely to be associated with the Carney complex, a possibility of such an association should always be born in mind, as consequences of missing syndromic neoplasms, such as cardiac myxoma, can be lethal.

Abstract: Gene rearrangements or fusions have emerged as critical oncogenic drivers in various cutaneous adnexal neoplasms. This review offers a comprehensive overview of both established and recently identified molecular alterations, with a specific focus on gene fusions. Key alterations discussed include YAP1 rearrangements, CRTC1::MAML2 fusions, BRD3 rearrangements, MYB::NFIB fusions, ETV6::NTRK3 fusions, and PLAG1 rearrangements, alongside rarer fusion transcripts, such as MEF2C::SS18 , FOXK1::GRHL1/2 , GPS2::GRHL , and RARA::NPEPPS . The article highlights the significance of these genetic changes in tumor biology and their potential therapeutic implications for locally advanced and metastatic skin adnexal tumors. It also addresses diagnostic challenges and molecular distinctions, providing updated insights into adnexal tumors driven by these gene fusions.

Background: Although cutaneous squamous cell carcinoma (SCC) arising from lichen planus is rare, hypertrophic lichen planus (HLP) accounts for most of these malignant transformations. Although the mechanism of malignant pathogenesis remains unknown, reports of similar premalignant conditions suggest a potential role of tumor suppressor p16. This is the first study to our knowledge to examine p16 expression in HLP in comparison to cutaneous invasive SCC and normal skin and its implications for malignant transformation.

Methods: p16 immunohistochemistry of HLP (n = 34) was performed alongside location-matched well-differentiated SCC (WDSCC) and normal skin. Percentage of positive cells, nuclear and cytoplasmic staining intensity, and staining distribution patterns were reviewed by 2 Board-certified dermatopathologists.

Results: HLP and WDSCC both showed an increased percentage of positive cells compared with normal skin ( P < 0.001). Cytoplasmic p16 was overexpressed in HLP compared with WDSCC ( P < 0.05). Most cases of HLP and WDSCC demonstrated stronger basal and suprabasal keratinocyte staining with weaker superficial staining. In WDSCC, a predominant pattern of focal cytoplasmic margination of staining along the cellular periphery was observed.

Conclusions: Our finding of cytoplasmic p16 overexpression in HLP suggests a potential mechanism of p16-mediated cell cycle dysregulation seen in other premalignant conditions. p16 overexpression seems to be a possible contributor in the malignant transformation of HLP to SCC.

Background: Bowen disease and bowenoid actinic keratosis are difficult to distinguish due to overlapping histopathology. This study evaluates the role of p16, p53, and MIB-1 staining patterns in differentiating high-chronic sun damage (H-CSD) and low-chronic sun damage bowenoid lesions.

Methods: Sixty extragenital in situ squamous cell carcinomas were included. Lesions with elastosis were considered H-CSD. P16, p53, and MIB-1 staining patterns were classified as block, gradient, or focal.

Results: Seventy-two percent of lesions were H-CSD. Full-thickness dysplasia was observed in all lesions, and basal layer involvement in 97%. P16 staining was positive in 80%, matching areas of higher atypia, with block pattern more frequent in H-CSD (58% vs. 47%, P = 0.047). P53 was positive in 47%, with block pattern more common in H-CSD (40% vs. 18%, P = 0.02). MIB-1 was positive in all cases. P16 and MIB-1 patterns coincided in 75%, independently of sun exposure.

Conclusions: P16 and p53 expression may be less frequent in bowenoid lesions than previously described. Histopathological features like basal layer and adnexal or follicular involvement may not differentiate H-CSD from low-chronic sun damage lesions or Bowen disease from bowenoid actinic keratosis. Variations in p16, p53, and MIB-1 staining could indicate different dysplasia pathways, although further studies are needed to clarify their prognostic significance.

Abstract: Nonmelanoma malignancies associated with congenital melanocytic nevi (CMN) are extremely rare, with only 12 reported cases of rhabdomyosarcoma (RMS) to date. We present 2 additional cases of RMS arising in giant CMN, with immunohistochemical and molecular biologic investigations. The first case was a 32-year-old woman with a personal history of melanoma in giant CMN who, after successful treatment and long remission, presented with a new 1-cm nodule within the CMN. Microscopically, the atypical areas exhibited a round cell/alveolar morphology with immunoreactivity for desmin and myogenin, and lacked PAX3/7::FOXO1 fusions typical for alveolar RMS on a reverse transcription polymerase chain reaction analysis. An identical NRAS p.Q61R mutation with comparable variant allele frequency (32% and 44%) was identified in both the nevus and the RMS tissue by next-generation sequencing. The second patient was a 5-year-old girl with a rapidly growing, bleeding, ulcerated 3 × 4 cm interscapular mass within a giant CMN that histologically seemed as a proliferation of pleomorphic spindle, polygonal and epithelioid cells with marked pleomorphism immunoreactive for myogenin, muscle-specific actin, and smooth muscle actin. Next-generation sequencing yielded an HRAS p.Q61R mutation with limited variant allele frequency (7%) in the RMS component, while ATRX p.Q2193* variant was detected in the nevus. Our study is apparently the first report of NRAS and HRAS mutations in tumors with RMS phenotype arisen in CMN.

Abstract: Preferentially Expressed Antigen in Melanoma (PRAME) immunohistochemistry has been found to be relatively sensitive and specific for the diagnosis of melanoma, although the detection of PRAME positivity in some melanocytic nevi is a significant limitation. This study was designed to investigate the features of common melanocytic nevi showing PRAME staining, encountered in routine community practice. We reviewed all pathology reports on common melanocytic nevi seen in routine practice for a 1-month period and found that 7.1% of nevi stained with PRAME were considered positive by the original reporting pathologist. A total of 41 PRAME-positive nevi (representing 4.7% of nevi) and a control group of 43 PRAME-negative nevi collected during the same period were identified. The histologic features were reviewed, and the diagnosis and PRAME staining were recorded in a masked fashion by 3 dermatopathologists. Our results suggest that caution is warranted in the interpretation of PRAME in the assessment of small lentiginous melanocytic nevi with a low level of suspicion for melanoma, because these are not infrequently PRAME positive. We found a statistically significant association between the presence of solar elastosis and lentiginous growth pattern, and PRAME status ( P < 0.01). When comparing the original diagnosis with the reviewer's diagnosis, the original diagnosis was severely atypical in 54% of PRAME-positive cases, while only 7% were considered to show severe atypia on review masked to PRAME status ( P < 0.001). There was no such discrepancy among PRAME-negative cases (9% vs. 19%, considered severely atypical). This finding provides evidence of a "PRAME bias" in the interpretation of melanocytic lesions with no or mild atypia, whereby such lesions are classified as severely atypical when PRAME is positive, likely with the intention of prompting re-excision.

Abstract: Acute myeloid leukemia is a cancer involving uncontrolled proliferation of hematopoietic cells. Cutaneous involvement is referred to as leukemia cutis (LC). The histopathologic presentation of LC is variable, and may present with perivascular, periadnexal, dermal, or subcutaneous infiltrate. Epidermotropism is notably absent. We report an unusual case of acute myeloid LC with epidermotropism in a 68-year-old man. A punch biopsy revealed a mononuclear myeloblast infiltrate involving the dermis and subcutaneous tissue. The epidermis was focally acanthotic, with several vesicles and atypical epidermotropic cells. Mitotic figures and apoptotic cells were present. Immunohistochemistry showed the blasts to be positive for CD56, CD123, and lysozyme, and weakly positive for CD4 and CD163. Negative immunostaining included CD3, CD20, CD34, TdT, and CD117. Epstein-Barr virus in situ hybridization was negative. A bone marrow biopsy revealed the same myeloblast population with identical phenotype to the skin. The blasts were negative for CD34, CD117, CD3, CD19, CD163, CD68, CD61, myeloperoxidase, pankeratin, E-cadherin, CD4, and transcription factor 4. A diagnosis of acute myeloid leukemia with monocytic differentiation and leukemia cutis was established. These findings suggest that the differential diagnosis for conditions with epidermotropism may be even broader than previously thought.

Abstract: Disseminated hypopigmented keratosis is a rare distinct clinical entity. This report describes the case of a 19-year-old male patient who developed disseminated hypopigmented keratosis 2 months after autologous hematopoietic stem cell transplantation for pineal choriocarcinoma. The patient displayed numerous tiny whitish or depigmented macules and papules on the chest, back, posterior neck, shoulders, arms, and thighs, closely resembling lichen nitidus. Microscopically, the lesion was orthokeratotic, acanthotic, and flat-bottomed without cytological atypia. Dermal inflammation was minimal. Fontana-Masson, Melan-A, and sex-determining region Y-box transcription factor 10 staining revealed a significant decrease in both basal melanin content and the number of melanocytes. The patient was initially administered a topical agent comprising hydrocortisone and urea, which exhibited minimal improvement. This case report suggests that disseminated hypopigmented keratosis may be a rare cutaneous manifestation of autologous hematopoietic stem cell transplantation. Additional research is necessary to gain a more comprehensive understanding of the pathogenesis and the clinical course of this disease.