Tumor-induced reshuffling of lipid composition on the endoplasmic reticulum membrane sustains macrophage survival and pro-tumorigenic activity.

Tumor-associated macrophages (TAMs) display pro-tumorigenic phenotypes for supporting tumor progression in response to microenvironmental cues imposed by tumor and stromal cells. However, the underlying mechanisms by which tumor cells instruct TAM behavior remain elusive. Here, we uncover that tumor-cell-derived glucosylceramide stimulated unconventional endoplasmic reticulum (ER) stress responses by inducing reshuffling of lipid composition and saturation on the ER membrane in macrophages, which induced IRE1-mediated spliced XBP1 production and STAT3 activation. The cooperation of spliced XBP1 and STAT3 reinforced the pro-tumorigenic phenotype and expression of immunosuppressive genes. Ablation of XBP1 expression with genetic manipulation or ameliorating ER stress responses by facilitating LPCAT3-mediated incorporation of unsaturated lipids to the phosphatidylcholine hampered pro-tumorigenic phenotype and survival in TAMs. Together, we uncover the unexpected roles of tumor-cell-produced lipids that simultaneously orchestrate macrophage polarization and survival in tumors via induction of ER stress responses and reveal therapeutic targets for sustaining host antitumor immunity.

Line-field confocal optical coherence tomography of xanthogranuloma: Correlation with vertical and horizontal histopathology.

Line-field confocal optical coherence tomography (LC-OCT) is a new noninvasive technique for a real-time, vertical, and horizontal imaging of the skin at cellular resolution. A 47-year-old female presented with a 6-month history of an asymptomatic yellowish papule. LC-OCT evaluation was able to show the diagnostic microscopic features of xanthogranuloma and showed an excellent correlation with vertical and horizontal histopathological sections by revealing enlarged dermal papillae containing multiple, bright roundish giant cells, corresponding to foamy histiocytes, and giant cells characterized by a dark center surrounded by a highly hyper-refractile peripheral ring, corresponding to Touton cells. LC-OCT may represent a valid, noninvasive alternative to histopathological examination in clinically atypical cases of xanthogranuloma.

Coexistence of three nevus lipomatosus cutaneus superficialis with typical, cutaneous adenolipoma-like, and dermal spindle cell lipoma-like histopathological features in a patient.

We report an unique case of a patient who showed coexistence of three nevus lipomatosus cutaneus superficialis (NLCS) with typical, cutaneous adenolipoma (AL)-like, and dermal spindle cell lipoma (SCL)-like histopathological features. A 53-year-old woman presented with a 20-year history of skin-colored and slightly elevated nodules. These lesions were separately located on the lateral side (lesion 1) and medial side (lesion 2) of her left buttock and on her right thigh (lesion 3). Microscopically, all were ill-defined dermal lesions with some subcutaneous involvement and were mostly composed of mature adipocytes. The adipocytes formed small aggregates around blood vessels in the upper dermis. Lesions 1, 2, and 3 were diagnosed as NLCS, and additional features were recognized in lesions 2 and 3. Lesion 2 revealed eccrine glands and ducts amongst the lipomatous component, as seen in cutaneous AL. Lesion 3 had scattered CD34-positive spindle cells, which is representative of dermal SCL. These appearances were considered to be on the morphological spectrum of NLCS. In all three lesions, CD34-positive cells proliferated between the upper dermal blood vessels and their peripheral mature adipocytes. This pathological finding could be principal in NLCS and might be associated with its pathogenesis.

The utility of PRAME immunohistochemistry in the evaluation of challenging melanocytic tumors.

BACKGROUND: PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has demonstrated high specificity for unequivocal melanomas; however, its utility in ambiguous melanocytic neoplasms has yet to be fully elucidated. METHODS: Cases of challenging melanocytic neoplasms were subclassified into one of three categories: challenging, favor benign (FB), challenging, cannot be subclassified (CCS), or challenging, favor malignant (FM). Using a previously published system, whereby cases with diffuse staining (>75%) were considered positive, scoring of PRAME was performed. Additionally, tumors with hotspot staining were also considered positive. RESULTS: Sixteen out of 85 tumors showed positive staining representing 5% of FB tumors, 24% of CCS tumors, and 47% of FM. In FB and CCS tumors, positive staining was mainly encountered in atypical intraepidermal melanocytic proliferations and spitzoid neoplasms. The specificity of positive PRAME staining was 95% and its concordance with the final diagnostic interpretation was 75%. CONCLUSIONS: PRAME positivity is more common in neoplasms favored to be malignant by histopathologic evaluation. Its clinical utility may include early diagnosis of incipient melanoma in situ. Rarely, benign melanocytic neoplasms could show diffuse expression of PRAME, and additional studies are needed to determine optimal utilization. Lastly, hotspot staining may increase its sensitivity without much compromise in specificity.

Clinical and histopathological features of pagetoid Spitz nevi of the thigh.

BACKGROUND: Pagetoid Spitz nevus is a rare subtype of Spitz nevus usually found on the lower extremities, particularly on the thigh of women. As a rare and under-recognized entity that can be misdiagnosed as melanoma, further characterization of clinical and histopathological features is needed to improve its recognition. METHODS: A retrospective analysis of all melanocytic neoplasms from the thigh diagnosed over a 3-year period. RESULTS: Fifty-five (15.4%) of the 357 melanocytic neoplasms on the thigh were Spitz nevi, the majority of them occurring in women (87.3%). Of the 55 Spitz nevi, 33 (60.0%) were pagetoid Spitz nevi, 14 (25.5%) were Reed nevi, and eight (14.5%) were conventional Spitz nevi. The mean age of patients with pagetoid Spitz nevi was 47.2, the majority being women (84.9%). Pagetoid Spitz nevi were small, with a mean histopathologic diameter of 4 mm, and often junctional (63.6%). Compared to Clark nevi of the thigh, pagetoid Spitz nevi comprised significantly more solitary melanocytes with a greater degree of scatter. CONCLUSIONS: These results suggest that Spitz nevi and, in particular, pagetoid Spitz nevi constitute a significant percentage of nevi on the thigh. Previously reported benign clinical and histopathological features of pagetoid Spitz nevi are confirmed in this study.

BRAF fusion Spitz neoplasms; clinical morphological, and genomic findings in six cases.

BACKGROUND: Fusions involving the BRAF gene are responsible for 5% of Spitz neoplasms. To better characterize them, we report the clinical, morphological, and genomic findings of six BRAF fusion Spitz tumors. METHODS: The morphological, clinical, and molecular findings of six BRAF fusion Spitz neoplasms assessed by next generation sequencing (NGS) were compared to a control set of Spitz without BRAF fusions. RESULTS: BRAF fusion Spitz tumors had frequent predominance of epithelioid morphology (4/6 cases), frequent high-grade nuclear atypia and pleomorphism (5/6 cases), and a frequent desmoplastic base (3/6 cases). Five of six cases were diagnosed as atypical Spitz tumor and one as Spitz nevus. All cases had uneventful clinical follow-up. There were five different fusion partners, with CLIP2 being the most frequent. Secondary pathogenic mutations were frequent and chromosomal copy number changes were seen in three of six cases by an NGS platform. CONCLUSIONS: BRAF fusions Spitz usually have epithelioid morphology, high-grade nuclear atypia, and desmoplasia. Chromosomal copy number changes are not infrequent. While our cases had uneventful follow-up, a meta-analysis of the literature suggests that among the fusion subtypes associated with Spitz tumors, they are among the subgroups more likely to develop distant metastasis.

Molecular analysis of atypical deep penetrating nevus progressing to melanoma.

Deep penetrating nevi (DPN) are dermal-based, heavily pigmented melanocytic proliferations primarily resulting from mutations in B-catenin and BRAF or, less commonly, NRAS. DPNs are considered to be intermediate grade tumors which are stable with low risk of malignant transformation. The precise risk for transformation is unknown. Only rare cases of DPN progressing to melanoma have been described. We present a case of a 53-year-old female with a blue-black thigh lesion, on histopathology illustrating a melanocytic proliferation with morphology most consistent with a DPN progressing to melanoma. Targeted next generation sequencing performed on both the atypical melanocytic proliferation and melanoma components showed NRAS and CTNNB1 mutations but no evidence of TERT promoter mutation or chromosomal copy number aberrations. The melanoma had additional mutations including a hotspot TERT promoter mutation as well as unbalanced chromosomal copy number aberrations. This report details the progression of DPN to melanoma through a prominent ultraviolet signature and acquisition of genetic aberrations. While the vast majority of DPNs are benign stable nevi, there are rare examples, which may progress to melanoma. This report documents a case and shows the molecular evolution by which the tumor transformed to melanoma.

Primary cutaneous biphasic sarcomatoid basal cell carcinoma with myoepithelial carcinoma differentiation: A new variant.

Isolated cases of basal cell carcinoma (BCC) with partial myoepithelial component have been described. However, myoepithelial differentiation has not been described in sarcomatoid basal cell carcinomas, which usually show features resembling osteosarcoma, chondrosarcoma, or leiomyosarcoma. We report a case of an 87-year-old man with a forehead lesion that histologically showed a minor component of conventional nodular BCC in transition with a major biphasic sarcomatoid growth composed of invasive spindle-cell and epithelial-like components, the latter with a reticular pattern and scattered ductal structures. Both components showed cytological atypia and high mitotic rate (26/10HPF), with atypical mitotic figures. BER-EP4 immunostaining was exclusively found in the nodular BCC component whereas the sarcomatoid component revealed immunostaining for α-smooth muscle actin (SMA), muscle-specific actin (MSA), calponin, and p63 in both epithelial-like and spindle-cell populations. Focal immunoreactivity was observed in the epithelial component for S100 and glial fibrillary acidic protein (GFAP). Furthermore, EWSR1-PBX1 gene fusion was also detected. This is to our knowledge, the first fully documented case of biphasic sarcomatoid BCC with myoepithelial carcinoma differentiation.

Accuracy of tele-consultation on management decisions of lesions suspect for melanoma using reflectance confocal microscopy as a stand-alone diagnostic tool.

BACKGROUND: Diagnostic accuracy of reflectance confocal microscopy (RCM) as a stand-alone diagnostic tool for suspect skin lesions has not been extensively studied. OBJECTIVE: Primary aim was to measure experts' accuracy in RCM-based management decisions. Secondary aim was to identify melanoma-specific RCM features. METHODS: The study enrolled patients ≥18 years that underwent biopsy of skin lesions clinically suspected to be melanoma. One hundred lesions imaged by RCM were randomly selected from 439 lesions prospectively collected at four pigmented lesion clinics. The study data set included 23 melanomas, three basal cell and two squamous cell carcinomas, 11 indeterminate melanocytic lesions and 61 benign lesions including 50 nevi. Three expert RCM evaluators were blinded to clinical or dermoscopic images, and to the final histopathological diagnosis. Evaluators independently issued a binary RCM-based management decision, 'biopsy' vs. 'observation'; these decisions were scored against histopathological diagnosis, with 'biopsy' as the correct management decision for malignant and indeterminate lesions. A subset analysis of 23 melanomas and 50 nevi with unequivocal histopathological diagnosis was performed to identify melanoma-specific RCM features. RESULTS: Sensitivity, specificity and diagnostic accuracy were 74%, 67% and 70% for reader 1, 46%, 84% and 69% for reader 2, and 72%, 46% and 56% for reader 3, respectively. The overall kappa for management decisions was 0.34. Readers had unanimous agreement on management for 50 of the 100 lesions. Non-specific architecture, non-visible papillae, streaming of nuclei, coarse collagen fibres and abnormal vasculature showed a significant association with melanoma in the evaluation of at least two readers. CONCLUSIONS: Reflectance confocal microscopy tele-consultation of especially challenging lesions, based on image review without benefit of clinical or dermoscopy images, may be associated with limited diagnostic accuracy and interobserver agreement. Architectural and stromal criteria may emerge as potentially useful and reproducible criteria for melanoma diagnosis.

Intracytoplasmic eosinophilic inclusion bodies with embryonic folliculosebaceous-apocrine unit differentiation in syringocystadenoma papilliferum.

We describe a case of syringocystadenoma papilliferum (SCAP) with a unique histopathology. A 50-year-old Japanese woman presented with a pedunculated tumor in the pubic region. Histopathological examination showed that the tumor was composed of basaloid cell proliferation interconnecting from the epidermis to the dermis. Ductal structures in the tumor were lined by club-shaped columnar cells with apical snouts. Interestingly, numerous vacuolated cells with hyaline globule-like cytoplasmic inclusions were present among the columnar cells, the content of which was identified as sialomucin. Electron microscopy revealed that the vacuolated cytosol of luminal cells represented intracytoplasmic lumens with a structure similar to embryonic apocrine ducts. We assumed that this case represents a rare variant of SCAP that had differentiated toward the embryonic folliculosebaceous-apocrine unit.

Metallic copper nanoparticles induce apoptosis in a human skin melanoma A-375 cell line.

In two earlier communications (Chatterjee et al 2012 Nanotechnology 23 085103, Chatterjee et al 2014 Nanotechnology 25 135101), we reported the development of a simple and unique method of synthesizing highly stable metallic copper nanoparticles (Cu NPs) with high antibacterial activity. Here we report on the cytotoxic potency of the NPs against cancer cells. The value of the IC50 dose of the Cu NPs against human skin cancer cell A-375 was found to be 1.71 µg ml-1 only, which was much less than values reported so far, and this concentration had no cytotoxic effect on normal white blood cells. The NPs caused (i) lowering of cell membrane rigidity, (ii) DNA degradation, (iii) chromosomal condensation, (iv) cell cycle arrest in the G2/M phase, (v) depolarization of the mitochondrial membrane and (vi) apoptosis of cells. Cellular apoptosis occurred in the caspase-9-mediated intrinsic pathway. This study revealed that our Cu NPs had high anticancer properties by killing tumor cells through the apoptotic pathway. Since this particle has high antibacterial activity, our Cu NPs might be developed in future as a dual action drug-anticancer as well as antibacterial.

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma.

BACKGROUND: Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE: We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS: This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS: Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS: Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION: Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

Ghost cells in pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor: histological, immunohistochemical, and ultrastructural study.

BACKGROUND: Pilomatrixoma, craniopharyngioma, and calcifying cystic odontogenic tumor are the main entities presenting ghost cells as an important histological feature, in spite their quite different clinical presentation; it seems that they share a common pathway in the formation of these cells. The aim of this study is to examine and compare the characteristics of ghost and other cells that form these lesions. METHODS: Forty-three cases including 21 pilomatrixomas, 14 craniopharyngiomas, and eight calcifying cystic odontogenic tumors were evaluated by immunohistochemistry for cytokeratins, CD138, ß-catenin, D2-40, Glut-1, FAS, CD10 and also by scanning electron microscopy. RESULTS: The CKs, CD138, ß-catenin, Glut-1, FAS, and CD10 were more often expressed by transitional cells of craniopharyngioma and calcifying cystic odontogenic tumor, compared with pilomatrixoma. Basaloid cells of pilomatrixoma showed strong positivity for CD138 and CD10. Differences on expression pattern were identified in transitional and basal cells, as ghost cells were negative for most antibodies used, except by low expression for cytokeratins. By scanning electron microscopy, the morphology of ghost cells were similar in their fibrillar cytoplasm, but their pattern varied from sheets in pilomatrixoma to small clusters in craniopharyngioma and calcifying cystic odontogenic tumor. CONCLUSIONS: Mechanisms involved in formation of ghost cells are unknown, but probably they follow different pathways as protein expression in the basal/transitional cells was not uniform in the three tumors studied.

Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma cell line.

Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to basement membranes. For the first time, we present a method to prepare a fraction from human cultured cells that are highly enriched in hemidesmosomal proteins. Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of hemidesmosomes was observed when these cells were cultured for more than 10 days in a commercial serum-free medium without supplemental calcium. Electron microscopy demonstrated that numerous electron-dense adhesion structures were present along the basal cell membranes of DJM-1 cells cultured under the aforementioned conditions. After removing cellular materials using an ammonia solution, hemidesmosomal proteins and deposited extracellular matrix were collected and separated by electrophoresis. There were eight major polypeptides, which were determined to be plectin, BP230, BP180, integrin α6 and ß4 subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we designated this preparation as a hemidesmosome-rich fraction. This fraction contained laminin-332 exclusively in its unprocessed form, which may account for the promotion of laminin deposition, and minimal amounts of Lutheran blood group protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich fraction would be useful not only for biological research on hemidesmosomes but also for developing a serum test for patients with blistering skin diseases.

HISTOLOGIC, IMMUNOHISTOCHEMICAL, AND ELECTRON MICROSCOPIC CHARACTERIZATION OF A MALIGNANT IRIDOPHOROMA IN A DWARF BEARDED DRAGON (POGONA HENRYLAWSONI).

A dwarf bearded dragon (Pogona henrylawsoni) was presented with a white subcutaneous mandibular mass and multiple nodules in the oral mucosa, heart, liver, kidney, intestine, and visceral fat. Histologically, the tumor consisted of densely packed spindle-shaped cells with brow intracytoplasmic pigment that exhibited white-blue birefringence with polarized light. Immunohistochemical staining was negative for S-100 and weakly positive with melan A. Electron microscopic examination revealed cytoplasmic irregular and oblong empty spaces, laminated and often arranged into short stacks, compatible with reflecting platelet profiles typically seen in iridophores. However, in unstained ultrathin sections, electron-dense crystalline material was present, which filled the empty spaces described for stained sections before. Based on histology, immunohistochemistry, and biologic behavior, a malignant iridophoroma was diagnosed. To the authors' knowledge, iridophoromas in lizards have rarely been characterized by using electronic microscopy. Moreover, this is the first description of an iridophoroma in a dwarf bearded dragon.

A novel hypoxia-associated subset of FN1 high MITF low melanoma cells: identification, characterization, and prognostic value.

In many human cancers, the epithelial-to-mesenchymal transition has an important role in the induction of cancer stem-like cells, and hence, in the causation of intratumoral heterogeneity. This process, also referred to as mesenchymal mimicry, is, however, only poorly understood in melanoma and histological correlation is still lacking. In an immunohistochemical analysis of a large prospective series of 220 primary and metastatic melanomas for the well-known epithelial-to-mesenchymal transition marker FN1, we observed melanoma cells with high FN1 expression in metastases with ischemic necrosis, but rarely or not at all in samples lacking evidence of hypoxia. In a blinded, retrospective series of 82 melanoma metastases with 10-year follow-up, the presence of clusters of these FN1(high) melanoma cells correlated significantly with shortened melanoma-specific survival, highlighting the prognostic value of their presence. We describe in detail the unique light- and electron-microscopic features of these FN1(high) melanoma cells, enabling their identification in routinely hematoxylin-and-eosin-stained sections. In addition, by laser microdissection and subsequent gene expression analysis and immunohistochemistry, we highlight their distinctive, molecular phenotype that includes expression of various markers of the epithelial-to-mesenchymal transition (eg, ZEB1) and of melanoma stem-like cells (eg, NGFR), and lack of immunoreactivity for the melanocytic marker MITF. This phenotype could be reproduced in vitro by culturing melanoma cells under hypoxic conditions. Functionally, the hypoxic microenvironment was shown to induce a more migratory and invasive cell type. In conclusion, we identified a novel clinically relevant FN1(high)MITF(low) cell type in melanoma associated with ischemic necrosis, and propose that these cells reside at the crossroad of the epithelial-to-mesenchymal transition and stem-like cell induction, plausibly triggered by the hypoxic environment.

Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy.

BACKGROUND: The current guidelines for the management of basal cell carcinoma (BCC) suggest a different therapeutic approach according to histopathologic subtype. Although dermatoscopic and confocal criteria of BCC have been investigated, no specific studies were performed to evaluate the distinct reflectance confocal microscopy (RCM) aspects of BCC subtypes. OBJECTIVES: To define the specific dermatoscopic and confocal criteria for delineating different BCC subtypes. METHODS: Dermatoscopic and confocal images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Frequencies of dermatoscopic and confocal parameters are provided. Univariate and adjusted odds ratios were calculated. Discriminant analyses were performed to define the independent confocal criteria for distinct BCC subtypes. RESULTS: Eighty-eight BCCs were included. Dermatoscopically, superficial BCCs (n=44) were primarily typified by the presence of fine telangiectasia, multiple erosions, leaf-like structures, and revealed cords connected to the epidermis and epidermal streaming upon RCM. Nodular BCCs (n=22) featured the classic dermatoscopic features and well outlined large basaloid islands upon RCM. Infiltrative BCCs (n=22) featured structureless, shiny red areas, fine telangiectasia, and arborizing vessels on dermatoscopy and dark silhouettes upon RCM. LIMITATIONS: The retrospective design. CONCLUSION: Dermatoscopy and confocal microscopy can reliably classify different BCC subtypes.

Inner gray halo, a novel dermoscopic feature for the diagnosis of pigmented actinic keratosis: clues for the differential diagnosis with lentigo maligna.

BACKGROUND: Pigmented actinic keratosis (PAK) is a frequent simulator of lentigo maligna (LM) on the face upon clinical and dermoscopic examination, leading to misdiagnosis and unnecessary excisions. LM and PAK share dermoscopic features, making it difficult to have a confident diagnosis of PAK only with current dermoscopic knowledge. OBJECTIVE: We sought to evaluate sensitivity, specificity, and interobserver reproducibility of a novel dermoscopic feature, inner gray halo (IGH), and establish its histopathological and confocal correlations. METHODS: Dermoscopists blinded to histopathological diagnosis evaluated 58 PAK and 21 LM for the presence of IGH and dermoscopy parameters. Areas exhibiting IGH were marked and imaged with reflectance confocal microscopy before sampling for histopathologic correlation. Reflectance confocal microscopy and transverse histologic sectioning were performed in 14 of 79 cases. RESULTS: IGH was present in 53 of 58 (94.1%) PAK and in 5 of 21 (23.8%) LM in our series (sensitivity 91.4%; specificity 71.4%; positive predictive value 89.8%). Interobserver agreement was excellent (Kappa 0.846). Through transverse and perpendicular histologic sections, a dermoscopic-histologic-confocal correlation of IGH was established. LIMITATIONS: A larger test set is needed to further validate the use of IGH in the differential diagnosis of PAK and facial pigmented lesions. CONCLUSION: IGH is a novel dermoscopic parameter useful for the differentiation of PAK from LM on the face.

Eruptive dermal clear cell desmo-plastic mesenchymal tumors with perivascular myoid differentiation in a young boy. A clinical, histopathologic, immunohistochemical and electron microscopy study of 17 lesions.

Clear cell tumors of the skin are observed in a wide variety of benign and malignant conditions with different histogenesis, sharing the presence of cells with abundant clear cytoplasm. Herein, we report the clinicopathologic features of a healthy young patient affected by asymptomatic, eruptive and disseminated, benign clear cell dermal tumors since early infancy. Neither family history nor genetic testing and counseling provided further useful information. The lesions were mostly confined to the face and lower left extremity with pink teleangiectatic papules and small nodules. Over a 4-year period, a total of 16 different cutaneous lesions were biopsied and histopathologic and immunohistochemical studies carried out; an additional lesion was also removed for electron microscopy examination. Histopathology evidenced multiple perivascular growths of spindle to oval and round cells intermingled with clear/granular cells throughout the dermis, with prominent desmoplasia and numerous capillary-like vessels with focal hemangiopericytoma-like features. Immunohistochemical neoplastic cells were uniformly positive for h-caldesmon and focally smooth muscle α-actin and CD13 indicating myoid differentiation whereas the consistent diffuse cytoplasmic staining for lysosome antigen, such as CD68PG-M1 and NKI/C3 along with the ultrastructural findings supported the view of a lysosome-mediated apoptotic process. The differential diagnosis with other clear cell cutaneous neoplasms is discussed.