A rare case of cutaneous pseudoglandular schwannoma.

Schwannomas are benign tumors that arise from the peripheral nerve sheath. Many variants of schwannomas exist, including plexiform, epithelioid, cellular, glandular, and ancient. The pseudoglandular subtype is extremely rare, as fewer than five cases of cutaneous pseudoglandular schwannomas have been reported based on our literature review. Herein, we report a case of a 64-year-old female who presented with a skin-colored nodule on her right arm for several years. Histopathology showed a superficial and deep dermal nodulocystic neoplasm composed of epithelioid and spindle cells surrounded by a fibrous stroma. The epithelioid cells surrounded multiple spaces suggestive of glandular differentiation, although many of these spaces also contained serum and red blood cells, raising consideration for vascular differentiation. Multiple epithelial markers, including pancytokeratin and epithelial membrane antigen, were all negative, providing no support for an epithelial tumor with true ductal/glandular differentiation. In addition, CD31, CD34, smooth muscle actin, and desmin stains were negative in these spaces, making a vascular neoplasm or smooth muscle tumor unlikely. However, SOX10 and S-100 stains were positive, including in cells lining the pseudoglandular spaces, supporting the diagnosis of pseudoglandular schwannoma. Complete excision was recommended. This case highlights an extremely rare presentation of the pseudoglandular variant of schwannoma.

Disseminated and penile mpox with histopathologic correlation: Two separate case reports.

The 2022-2023 mpox outbreak is a global worldwide concern, especially since the virus was previously mainly localized regionally in Central and West Africa. The infection is typically self-limiting and transmitted by close contact/exposure with infected material. Recent cases have been known to present atypically without prodromal symptoms and initially with skin lesions. The histopathology of mpox lesions is rarely reported. Here, we present two middle-aged males presenting initially with painless skin lesions confirmed for mpox by nucleic acid amplification assay. Skin biopsies of the lesion were available for clinicopathologic correlation. Histopathology demonstrated ulceration with viral cytopathologic changes.

Malignant Melanoacanthoma.

ABSTRACT: Melanoacanthomas are benign variations of seborrheic keratosis that have been known to mimic other common benign and malignant skin lesions. Therefore, the diagnosis typically requires biopsy and careful histologic examination. Here, we present the case of a 25-year-old woman initially diagnosed clinically with an epidermal inclusion cyst, but, on biopsy and further evaluation, was found to have histological features of an atypical or malignant melanoacanthoma. Contrary to typical cases of melanoacanthoma, histologic evaluation revealed atypical findings consistent with malignancy, such as tumor necrosis, marked cytologic atypia and pleomorphism, and numerous mitoses, including atypical forms, features consistent with malignancy (ie, similar to a squamous cell carcinoma in these areas). This report highlights the importance of histological evaluation in diagnosis and treatment of skin lesions because atypical presentations often occur and can delay correct diagnosis and appropriate treatment.

The Dermatopathology Books Before Unna.

ABSTRACT: Unna's book on dermatopathology was the one that achieved the greatest recognition in medicine and influenced the largest number of dermatopathologists in Europe at that time. However, several previous texts also gathered the requirements to be considered dermatopathological books. In this manuscript, we briefly examine some of the most relevant features of the dermatopathology books written by Simon, Leloir and Vidal, Auspitz, Bärensprung, and Jackson.

Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis.

ABSTRACT: Basal cell carcinomas are one of the most common cutaneous carcinomas and show classical histologic features of basaloid nests with peripheral palisading. Pagetoid and intraepidermal spread has not been described in basal cell carcinoma to the best of our knowledge. We report 5 cases of basal cell carcinoma with classic histologic patterns and overlying basaloid nests and single intraepidermal tumor cells. A panel of immunostains were performed that included CK7, MOC31, CEA-m, EMA, androgen receptor, and Bcl2. Most of our cases were positive for both MOC31 and CK7, and all cases were negative for CEA-m and EMA excluding extramammary Paget disease, one of the most common differential diagnoses. These cases expand the spectrum of findings that can be seen in basal cell carcinoma and can help prevent misdiagnoses of basal cell carcinomas as more aggressive tumors.

Central Centrifugal Cicatricial Alopecia Associated With PDL1 Loss and Increased Expression of Caspase 3: A Case Series.

ABSTRACT: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that disproportionately affects patients with skin of color. Genetic studies have revealed that approximately 30% of CCCAs are associated with peptidyl arginine deiminase 3 misfolding mutations. Patients with CCCA usually have a poor prognosis with progressive and permanent hair loss. To further characterize CCCA, we evaluated the inflammatory milieu, PDL1, and caspase 3 expression. The data support the idea of CCCA being a CD4-predominant T-cell process. The loss of PDL1 and increase in caspase 3 expression raises the possibility of involvement of the PD1/PDL1 pathway in CCCA.

A rare case of cutaneous interdigitating dendritic cell sarcoma.

Interdigitating dendritic cell sarcomas (IDCSs) are aggressive tumors of dendritic cells, often presenting with lymphadenopathy. Fewer than 10 cases of primary cutaneous IDCS have been reported. Histopathologically, IDCS presents as atypical spindle cells with irregular nuclei, and therefore can be difficult to distinguish from melanoma, follicular dendritic cell sarcoma, and Langerhans cell tumors by H&E examination alone. We report a unique case of a man with cutaneous IDCS that was initially misdiagnosed as melanoma. Having previously undergone an excision of a reported "melanoma" on the neck, he presented with a new growth on the cheek. Histopathologic findings revealed an atypical dermal lymphohistiocytic infiltrate around vessels and cells forming nests along the dermal-epidermal junction. Immunohistochemical stains were strongly positive for S100, fascin, and lysozyme; on the other hand, CD1a, langerin, CD21, CD23, and SOX10 were negative. These immunohistochemical findings were consistent with IDCS, and the patient's prior biopsy specimen was then revisited. Similar staining revealed that lesion also to be a cutaneous IDCS. Follow-up imaging with PET scan was negative for metastases, supporting the diagnosis of primary cutaneous IDCS. Our findings contribute to the limited literature on cutaneous IDCS and highlight a potential pitfall in its diagnosis because of overlapping histopathologic features with melanoma.

Primary cutaneous epithelioid mesenchymal neoplasm with ACTB-GLI1 fusion: a case report.

Mesenchymal tumors harboring GLI1 gene abnormalities are a rare but distinctive group of neoplasms whose clinicopathologic features are currently evolving. In particular, examples of this tumor with ACTB-GLI1 gene fusion, tentatively termed ACTB-GLI1 epithelioid mesenchymal neoplasm (EMN), show a distinctive monomorphic round-to-epithelioid morphology, nested to trabecular pattern of growth, and S100+/SOX10-/SMA- immunophenotype. We report the first case of this entity arising exclusively in the skin. A 69-year-old man with no prior history of neoplasia presented with a 1.5-cm raised lesion on the left buttock. Histopathologic examination revealed a diffuse dermal proliferation of small, monomorphic, round-to-ovoid cells with hyperchromatic nuclei, focally enlarged nucleoli, and minimal eosinophilic to clear-staining cytoplasm. These cells were arranged in confluent nests and trabeculae in a background of fibrocollagenous to focally myxoid stroma. Immunohistochemical analysis revealed strong positivity for S100 and CD56, and negativity for SOX-10, SMA, Melan-A, HMB-45, and a variety of other markers. Based on the morphology and immunophenotype, molecular studies were performed, which revealed the presence of an ACTB-GLI1 fusion transcript, confirming the diagnosis. Given the morphologic overlap of this tumor with other cutaneous round cell neoplasms and its potential for malignant behavior, ACTB-GLI1 EMN is an important entity for pathologists to recognize.

PRAME immunohistochemistry of spitzoid neoplasms.

BACKGROUND: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. METHODS: Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. RESULTS: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. CONCLUSIONS: Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.

A case of histiocytoid angiosarcoma mimicking Rosai-Dorfman disease histopathologically.

There are very few documented cases of histiocytoid angiosarcoma in the literature. We report a rare case of histiocytoid angiosarcoma demonstrating emperipolesis, a histopathologic finding that mimics Rosai-Dorfman disease (RDD). A 77-year-old male presented with a subcutaneous nodule on his left forehead. Microscopic examination of the tumor revealed a dense lymphohistiocytic and plasmacytic infiltrate with large epithelioid cells, many of which showed abundant pale eosinophilic to foamy-appearing cytoplasm, and some of which displayed phagocytosis of intact inflammatory cells and erythrocytes. The tumor also showed significant cytologic atypia and pleomorphism. Immunohistochemical stains showed strong staining of the histiocytoid cells and focal anastomosing-like vascular spaces for CD31 and ERG-1, but were essentially negative for CD68, lysozyme, CD163, S100, and CD1a, consistent with a vascular endothelial tumor. This case expands the spectrum of findings that can be identified in angiosarcomas, and should help to prevent potential misdiagnosis as a less aggressive tumor such as RDD.

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Combined Poroma and Verruca Plantaris.

ABSTRACT: A 76-year-old female patient presented with a peculiar new exophytic-appearing, flesh-colored skin lesion on her left hallux. Owing to its atypical appearance, the neoplasm was biopsied. Histologic sections demonstrated numerous thickened, anastomosing cord-like structures composed of bland appearing adnexal keratinocytes attached to the epidermis and extending into the superficial dermis. Nearby areas exhibited papillomatosis, epidermal acanthosis, dense hyperparakeratosis, hypergranulosis, and superficial koilocytes, findings consistent with a verruca plantaris. A p16 stain was positive in many of the superficial epidermal keratinocytes. Human papillomavirus typing by in situ hybridization for the most common low-risk and high-risk types was also performed and was negative for these. We herein present an unusual case of a skin lesion which combines features of a poroma with a verruca plantaris. We further review what is known of the relationship between human papillomavirus and poroid neoplasms.

Multiple myxoid cellular neurothekeomas in a patient with systemic lupus erythematosus.

Cellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal-based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60-year-old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S-100, SOX-10, epithelial membrane antigen, desmin, smooth muscle actin, glial fibrillary acid protein, and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions.

KRAS 117N positive Rosai-Dorfman disease with atypical features.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare disease typically characterized by a histiocytic proliferation within lymph nodes, which is due to an unknown etiology. Extranodal involvement can occur, and it more rarely can involve the skin. RDD generally presents with an indolent nature and follows a benign disease course, although more aggressive cases have been reported. The condition predominately affects children and young adults. It is classically characterized by massive, bilateral painless lymphadenopathy and accumulation of CD68-positive, S100-positive, CD1a-negative histiocytes, with the presence of emperipolesis as a hallmark. Herein, we present an aggressive case in a 76-year-old male with past medical history significant for prostate cancer, who presented with a 7-month history of lymphadenopathy and new onset of multiple large abdominal wall, cutaneous, lymph node, liver, and lung masses, all of which were histopathologically atypical, but showed features consistent with RDD, including emperipolesis and strong S100 positivity. Molecular studies showed a KRAS 117N mutation, which has been recently reported in RDD. While most cases present as a benign tumor, this case demonstrated aggressive features clinically, showed partial response to MEK inhibitor immunotherapy in the setting of a KRAS mutation, and demonstrated atypical cytologic features on histopathology.

Case of Symptomatic Dermal Neurofibroma With Microcystic Features.

ABSTRACT: A neurofibroma is a benign neural tumor arising within a peripheral nerve sheath composed of Schwann cells, fibroblasts, and immune cells involved in the nerve. Microcystic elements have been rarely described in these tumors. Neurofibromas are classically described as unencapsulated tumors of interspersed spindle cells and mast cells in a hypocellular, myxoid stroma. These tumors are most commonly dermal and seen in almost all patients with neurofibromatosis type 1; however, they may also occur sporadically, as seen in our case here. We report a 23-year-old patient with no significant medical history who presented with a dome-shaped papule on her cheek. This slow-growing mass had been present for multiple years and was soft, inflamed, and painful. Shave biopsy was collected and sent for evaluation. The shave biopsy diagnosed a benign neural tumor with features of a rare microcystic neurofibroma. This unencapsulated tumor consisted of microcystic spaces lined by oval-shaped to spindle-shaped cells in a matrix of myxoid to collagenous-like areas. Scattered lymphocytes and mast cells were noted, with few true vessels enclosing red blood cells. The stromal cells and cells lining the microcystic spaces stained S100 and SOX-10 positive. These cells had limited CD34 staining; however, most microcystic spaces were negative. Only the few true vessels stained CD31 positive. It is important to distinguish the prominent microcystic features in neurofibromas versus schwannomas by the lack of encapsulation or Antoni A features with Verocay bodies, which are typical of the latter. Further differentiating neurofibromas versus malignant peripheral nerve sheath tumors is required, where the latter should exhibit much greater nuclear atypic, higher cellularity, necrosis, hemorrhage, and increased mitotic activity. Excision of this benign microcystic neurofibroma was not deemed necessary because of lack of clinical concern and recurrent lesions.

Atypical Fibroxanthoma Demonstrating HMB45+ Staining.

ABSTRACT: Immunohistochemistry is useful and often necessary for the diagnosis of many histopathological entities, including atypical fibroxanthoma (AFX), which is typically considered a diagnosis of exclusion after ruling out spindle cell melanoma, sarcomatoid carcinoma, and other spindle cell tumors. AFX is a superficial fibrohistiocytic tumor previously believed to be related to pleomorphic sarcoma (formerly known as malignant fibrous histiocytoma), but is now considered a distinct clinicopathological entity. AFXs commonly express CD68, smooth muscle actin, and lysozyme and are usually negative for melanocytic markers such as HMB45 and S100. However, immunohistochemistry can sometimes be misleading, especially when used without other relevant markers in making a histopathologic diagnosis. HMB45 is a glycoprotein marker of premelanosomes and is often helpful in identifying melanoma because it stains melanosomes in the epidermis, dermis, and nevi glycocomplexes. We report a case of AFX which was strongly positive for HMB45, but negative for all other melanocytic markers. This case emphasizes the potential pitfall of relying on a single immunohistochemical marker to make the diagnosis, especially of melanoma, and also is one of the only rare reported cases of AFXs which are HMB45+.

Ossifying Plexiform Tumor: A Case Report.

ABSTRACT: Ossifying plexiform tumor is an exceedingly rare cutaneous neoplasm with distinctive histologic features. The typical microscopic appearance is that of a well-circumscribed dermal lesion composed of spindled and epithelioid cells in a myxoid appearing matrix with a plexiform architecture associated with areas of ossification. The present report details the clinicopathologic features of an ossifying plexiform tumor involving the lower extremity of a 69-year-old man. The cutaneous lesion exhibited characteristic morphologic features of this entity. By immunohistochemistry, the tumor was negative for most markers assessed, but notably exhibited diffuse positivity for SATB2. No lesional recurrence was observed. The present case serves to expand on the limited existing knowledge regarding the clinicopathologic features of this uncommon tumor. The histogenesis of ossifying plexiform tumor remains unclear; however, the demonstration of SATB2 expression in this case suggests osteoblastic differentiation.

PAS and GMS utility in dermatopathology: Review of the current medical literature.

The American Society of Dermatopathology has established an Appropriate Use Criteria (AUC) Committee with the intention of establishing evidence-based recommendations regarding the appropriateness of various ancillary tests commonly utilized by dermatopathologists. Periodic acid Schiff (PAS) and Grocott (or Gomori) methenamine silver (GMS) stains represent some of the most commonly employed ancillary tests in dermatopathology. The utility of these tests was targeted for evaluation by the AUC. This literature review represents a comprehensive evaluation of available evidence for the utility of PAS and/or GMS staining of skin and nail biopsies. In concert with expert opinion, these data will be incorporated into future recommendations by the AUC for PAS and GMS staining in routine dermatopathology practice.

Rosai-Dorfman Disease-Like Reaction to Tattoo.

A 47-year-old white man presented with a 14-month history of an asymptomatic 2-cm, slow-growing nodular lesion on his left shin that arose in the background of a black tattoo. An excisional biopsy followed by histological examination revealed a prominent lymphohistiocytic infiltrate, with many large, foamy histiocytic cells containing intact inflammatory cells within their cytoplasm, findings consistent with emperipolesis, a feature typical of Rosai-Dorfman disease (RDD). By immunohistochemistry, S-100 (a marker that is positive in almost all cases of RDD) was negative, arguing against the diagnosis of RDD. In addition, prominent black tattoo pigment was seen in many areas, expanding the differential diagnosis to include an unusual reactive lymphohistiocytic response to the tattoo mimicking RDD. Histologically, RDD shows many plasma cells, neutrophils, lymphocytes, and histiocytes with abundant foamy cytoplasm that contains intact lymphocytes and other cells, a phenomenon described as emperipolesis. A wide variety of cutaneous reactions to tattoos have been described, including tenderness, burning pain, inflammation, and pruritus. However, histologic features suggestive of RDD as a reaction to tattoo pigment have not been previously described and should therefore also be considered as a potential rare reaction pattern to tattoos.

Multiple Scrotal Cysts Composed of Combined Syringomas and Epidermal Inclusion Cysts: A Previously Unreported Association.

Epidermal inclusion cyst (EIC) and syringoma are both benign lesions that are primarily asymptomatic and occur at various places on the body. Although both EIC and syringoma are common, their joint appearance has not been previously reported. These benign proliferations target different populations, and with differing clinical presentations. Syringomas tend to develop in young females as smaller multiple lesions, while EICs often present in older males as single or multiple variants that are typically larger in size. They also possess distinctive histopathological appearances that can used for their diagnosis. Furthermore, despite both having unclear etiologies, the involvement of the eccrine duct has been a proposed mechanism in the development of both lesions. Thus, further investigation of eccrine ducts in the pathology of these lesions can be the basis for assessing the association between EICs and syringomas. We report a unique case of a 16-year-old boy who presented to the clinic with multiple cysts (at least 20) on the scrotum, most of which consisted of both EIC and syringoma histologically. We are not aware of any previous reports of patients with multiple combined syringomas and EICs, and their potential association should be further explored.