A rare case of invasive melanoma likely arising from passenger melanocytes of a basal cell carcinoma.

Neoplasms consisting of different cell lineages within a single skin specimen are rare, yet well documented in the literature. However, to date, there appears to be no report of invasive melanoma arising directly from the passenger melanocytes of a basal cell carcinoma (BCC). We present a case of a 91-year-old male with a suspicious lesion on the ear. Histopathology and immunohistochemical staining revealed BCC closely intertwined with invasive melanoma that exhibited foci of chondroid differentiation. The melanoma appeared to arise from the benign-appearing passenger melanocytes of the BCC and lacked connection to the overlying epidermis or an in situ component. Multiple dermatopathologists reviewed the case and agreed that the most likely explanation for the histopathologic findings was that the invasive melanoma arose from the passenger melanocytes within the BCC.

Reflectance confocal microscopy for noninvasive examination of nonmelanocytic tumors and virus-associated skin lesions in organ transplant recipients.

BACKGROUND: Drug-induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus-associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. MATERIALS AND METHODS: A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. RESULTS: For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I + II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. CONCLUSION: Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus-associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post-transplantation, larger cohorts of patients are required to confirm and consolidate these findings.

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.

Basal cell carcinoma of the vulva: treatment with Mohs micrographic surgery.

Vulval basal cell carcinomas (BCCs) are rare, representing < 5% of vulval malignancies and 1% of all BCCs. They often present with nonspecific symptoms and features that lead to large, poorly circumscribed and late-presenting lesions. Current and conventional treatments used to treat vulval BCC include cryotherapy, imiquimod and excision. However, recurrence rates as high as 20% have been reported with these treatments. Furthermore, there are no current clinical guidelines for their management. We present the first reported series of patients with vulval BCC treated with Mohs micrographic surgery (MMS). We report seven cases of vulval BCC treated with MMS at a tertiary referral centre over 3 years. Follow-up was performed at 3 months and up to 3 years. Our series demonstrates that there were no postoperative complications, functional sequelae or recurrences up to the 3-year follow-up. We therefore recommend that MMS should be considered in the management of vulval BCCs.

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.

Infrastructure of the telocytes from tumor stroma in the skin basal and squamous cell carcinomas.

In this paper, we focus our interest on the ultrastructure of telocytes (TCs) present inside of tumor-stroma in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Tumor-stroma cooperation is necessary for tumor growth, invasive behavior and ectopic development of microtumors. There is a plethora of reports about the role of different stromal cell types in tumor evolution in the human body. In this line, almost nothing is known about the recently identified interstitial cell type called telocyte (TC). To our best knowledge, this is the first study to publish TCs in malignant tumors, namely BCC and SCC. Here, we described the infrastructural aspects of TCs as well as their relationships with other tumor stroma components. TC from the tumor stroma has cell body where the nucleus is located and exhibits two (rarely more) very long cell extensions of tens (over 60-100 µm) termed telopodes. A telopode appears as an alternation of very thin segments called podomers and dilated segments called podomes, which accommodate mitochondria, rough endoplasmic reticulum, cytoskeleton, caveolae, as well as coated vesicles. TCs establish homocellular junctions leading to a 3-D network inside of peritumoral stroma. TCs may play an important role in intercellular signaling via stromal synapses and shed microvesicle transfer. Comparative evaluation with normal dermal skin showed that telocytes from tumor stroma have a very restraint number of heterocellular junctions. The limitation of TCs heterocellular junctions suggests a possible involvement in induction of cell-cell communication alterations into the peritumoral stroma and, consequently, into the whole tumor mass.

Estudio inmunohistoquímico de la calretinina en el folículo piloso normal y neoplasias con diferenciación folicular / Immunohistochemical study of calretinin in normal hair follicles and tumors with follicular differentiation

Introducción. La inmunotinción selectiva con calretinina evidencia la capa más interna de la vaina radicularexterna del folículo piloso normal, difícil de distinguir con la tinción de hematoxilina-eosina. Objetivo. Conocer si calretinina nos permite identificar neoplasias anexiales con diferenciación hacia la vaina radicular externa del folículo piloso. Material y métodos. Hemos analizado el patrón de inmunotinción para calretinina en 49 biopsias de distintas neoplasias anexiales cutáneas con diferenciación folicular. Resultados. Quince de las 49 tinciones correspondían a tricolemomas/queratosis folicular invertida, observándose positividad con calretinina en el epitelio de las áreas más superficiales de la lesión y en los remolinos escamosos; 10 quistes tricolémicos con positividad en su pared, tres carcinomas basocelulares con positividad variable dependiendo del tipo de diferenciación folicular de cada variante, un panfoliculoma con positividad focal, dos hamartomas sebáceos infundíbulo-quísticos con positividad en el conducto excretor de las glándulas sebáceas, dos pilomatricomas y tres tumores tricolemales proliferantes con positividad en las capas celulares cercanas a la luz de las estructuras quísticas, 9 tricoblastomas/tricoepiteliomas, dos quistes infundibulares, un poro dilatado de Winer y dos acantomas de la vaina folicular resultaron negativos. Conclusión. El estudio inmunohistoquímico de la calretinina nos permite identificar neoplasias anexiales del folículo piloso o componentes de éste, con diferenciación hacia la vaina radicular externa del folículo piloso (AU)

Background. Selective immunostaining for calretinin labels the innermost layer of the outer root sheath of normal hair follicles, which is difficult to distinguish with hematoxylin-eosin staining. Objective. The aim of this study was to determine whether immunohistochemistry for calretinin allows identification of cutaneous adnexal tumors with follicular differentiation towards cells of the outer root sheath.Material and methods. We analyzed the staining pattern for calretinin by immunohistochemistry in 49 biopsies of cutaneous adnexal tumors with follicular differentiation. Results. Fifteen biopsies corresponded to trichilemmomas/inverted follicular keratosis and had staining for calretinin in the epithelium of the most superficial areas of the lesions and in squamous eddies. Ten were trichilemmalcysts, which displayed staining of the cyst wall. Three were basal cell carcinomas with variable staining according to the type of follicular differentiation in each variant. One was a panfolliculoma that had focal staining. Two were folliculosebaceous cystic hamartomas with staining of the excretory duct of the sebaceous glands. Two pilomatricomas and 3 proliferative trichilemmal tumors had positive staining in the cellular layers close to the lumen of the cystic structures. Nine trichoblastomas/trichoepitheliomas, 2 infundibular cysts, 1 dilated pore of Winer, and2 acanthomas of the follicular sheath were negative for calretinin. Conclusion. Immunohistochemistry for calretinin allows identification of cutaneous adnexal tumors of the hair follicle or a component of the follicle with differentiation towards cells of the outer root sheath (AU)

Discrimination of basal cell carcinoma from normal dermal stroma by quantitative multiphoton imaging.

We performed multiphoton fluorescence (MF) and second-harmonic generation (SHG) imaging on human basal cell carcinoma samples. In the dermis, basal cell carcinomas can be identified by masses of autofluorescent cells with relatively large nuclei and marked peripheral palisading. In the normal dermis, SHG from dermal collagen contributes largely to the multiphoton signal. However, within the cancer stroma, SHG signals diminish and are replaced by autofluorescent signals, indicating that normal collagen structures responsible for SHG have been altered. To better delineate the cancer cells and cancer stroma from the normal dermis, a quantitative MF to SHG index is developed. We demonstrate that this index can be used to differentiate cancer cells and adjacent cancer stroma from the normal dermis. Our work shows that MF and SHG imaging can be an alternative for Mohs' surgery in the real-time guidance of the secure removal of basal cell carcinoma.

Clear cell trichoblastoma: a clinicopathological and ultrastructural study of two cases.

Clear cell change in basal cell carcinomas is a well-recognized phenomenon, but is obviously rare in trichoblastomas. We present two cases of clear cell trichoblastoma in which clear cell change was very much prominent, and the results of an ultrastructural study intended to explore the basis of that feature. Both our patients were women, aged 56 and 77 years, who presented with solitary, slowly growing nodules that measured 3 to 5 cm in largest dimension and were located on the scalp and the flexor aspect of the lower arm. Microscopically, the tumors in both cases were symmetric, non-ulcerated, and composed of variably sized and shaped (cribriform, racemiform, strands, cords, nodules) aggregations of monomorphous basaloid epithelial cells that were associated with a specific trichogenic stroma. Common to both tumors was clear cell cytoplasm evident in the majority of the epithelial cells in one case and almost in the entire epithelial cell population in the other. In most epithelial aggregations the epithelial cells with clear cytoplasm often appeared columnar and were arranged in a palisade along a recognizable basal membrane, thus indicative of outer sheath differentiation at the bulb. There were other signs of follicular differentiation. Ultrastructurally, variably sized clusters of uniform small basaloid epithelial cells were separated from the stroma by a thin discontinuous basement membrane. In addition to the usual organelles, the cytoplasm contained fairly conspicuous tonofilaments and variably sized vacuoles devoid of a limiting membrane, located between the palisaded nuclei and the outer cell membrane. The majority of vacuoles were empty, although clumps of a finely granular substance were occasionally evident. No distinct lipid droplets or glycogen particles were identified. The basaloid cells were joined by scattered small desmosomes. These findings were consistent with trichilemmal differentiation at the bulb.

Basal cell carcinoma: biology, morphology and clinical implications.

Basal cell carcinoma (BCC) is the most common malignant neoplasm of humans. Rising dramatically in incidence in North America, as likely reflects changing habits of the population and a move from more northerly climes to the sunbelt of the Southern and Southwestern United States, the incidence is surely to rise even higher in the future. The last decade has seen significant advances in our understanding of BCC biology and novel approaches to therapy, which hinge upon accurate diagnosis and subclassification by pathologists. The purpose of this review article is to summate the research advances in our understanding of BCC biology and to acquaint pathologists and clinicians to the practical issues in BCC diagnosis and subclassification which flow there from.

Nucleolar organizer region staining patterns in paraffin-embedded tissue cells from human skin cancers.

BACKGROUND: Increased number of nucleoli (nucleolar organizer regions, NORs) with abnormal shapes and sizes, including small dots, has been used as prognostic tools to evaluate tumor proliferation levels and troublesome borderline lesions. In this study, NOR patterns of skin cancers were performed in the search of a valuable prognostic method to complement other histological procedures. METHODS: Paraffin-embedded tumor tissue was obtained from basal and squamous cell carcinomas, cutaneous malignant melanoma, premalignant lesions, and Skmel-28 human melanoma cells. Slices were dewaxed and AgNOR stained. The patterns were scored and submitted for statistical analyses. RESULTS: All types of cancer cells showed variable numbers of abnormally shaped nucleoli and dot-like structures. Only tumor cells presented four or more nucleoli, with or without dots, while 85% of the normal cells had one single NOR without dots. Most data were statistically significant when compared to normal cells. As a whole, squamous cell carcinoma and malignant melanoma tumor cells had less NOR alterations than basal cell carcinoma (BCC) tumor types. CONCLUSIONS: Changes in the number and shape of nucleoli present in malignant cells could be attributed to increased levels on rDNA transcription on cancer cells, besides abnormal remodeling of chromatin, which could disrupt proper nucleoli association. Increased genetic alterations on malignant basal cells could contribute to impair invasive and migration abilities of BCC tumors.

Basaloid carcinoma of the pancreas.

A case of basaloid carcinoma of the pancreas in a 26-year-old woman is reported. The tumour was constituted by solid nests of relatively uniform neoplastic cells with hyperchromatic nuclei and scant cytoplasm, showing distinct peripheral palisading. There were necrotic areas and deposition of hyaline material, suggesting a basement membrane-like substance. Small foci of clear-cut squamous differentiation were present. Tumour cells were positive for cytokeratin 14 and P63 and negative for neuroendocrine and acinic cell markers. Ultrastructurally, the tumour was constituted by polygonal cells with round nuclei containing clumped chromatin. Occasional tight junctions and keratin filaments were present. Basaloid carcinomas may arise in several sites of the body, the most frequent being the anus and oesophagus, and have poor clinical outcome. The present case appears to be, to the best of our knowledge, the first documented example in the literature of basaloid carcinoma of the pancreas.

Basaloid squamous cell carcinoma of the esophagus with or without adenoid cystic features.

CONTEXT: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare malignant tumor that morphologically could bear some resemblance to adenoid cystic carcinoma (ACC) originating from salivary glands. OBJECTIVE: The purpose of this study is to describe the histologic, immunohistochemical, and ultrastructural findings of BSCCs of the esophagus, with an emphasis on comparing tumors with or without adenoid cystic features. DESIGN: We reviewed 239 cases of primary esophageal carcinoma and detected 12 cases (5%) of BSCC. The light and electron microscopic findings and immunocytochemical localization of various antigens, including cytokeratins (AE1, AE3), carcinoembryonic antigen, epithelial membrane antigen, S100, smooth muscle actin, and p53, were examined in these BSCC cases. RESULTS: Histologically, all BSCCs were composed of solid lobules or nests of basaloid cells with well-demarcated outlines surrounded by a fibrous stroma. Seven of 12 tumors showed areas of ACC-like features, that is, cribriform-like pseudoglandular lumina formation and hyaline material surrounding the tumor nests, whereas the remaining 5 tumors were apparently pure basaloid carcinomas. These 2 groups of tumors were histologically and immunohistochemically identical in many aspects, namely, high-grade nuclei of the tumor cells with frequent mitoses, abundant comedo-type necrosis, focal areas of concomitant squamous differentiation, consistent immunoreactivity for cytokeratins, and poor or absent staining for S100 and smooth muscle actin. Ultrastructurally, the basaloid tumor cells exhibited relatively undifferentiated cellular characteristics and undeveloped cell organelles. CONCLUSION: Basaloid squamous cell carcinomas of the esophagus frequently have an intimate association with ACC-like patterns, but their histologic, immunocytochemical, and ultrastructural features correspond more to poorly differentiated squamous cell carcinoma than to salivary gland ACC. This distinction is important because genuine ACC is much less aggressive than BSCC.

Down-regulated PAR-2 is associated in part with interrupted melanosome transfer in pigmented basal cell epithelioma.

In pigmented basal cell epithelioma (BCE), there seems to be an abnormal transfer of melanized melanosomes from proliferating melanocytes to basaloid tumor cells. In this study, the interruption of that melanosome transfer was studied with special respect to the altered function of a phagocytic receptor, protease-activated receptor (PAR)-2 in the basaloid tumor cells. We used electron microscopy to clarify the disrupted transfer at the ultrastructural level and then performed immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to examine the regulation of a phagocytic receptor, PAR-2, expressed on basaloid tumor cells. Electron microscopic analysis revealed that basaloid tumor cells of pigmented BCE have a significantly lower population of melanosomes ( approximately 16.4%) than do normal keratinocytes located in the perilesional normal epidermis ( approximately 91.0%). In contrast, in pigmented seborrheic keratosis (SK), a similarly pigmented epidermal tumor, the distribution of melanin granules does not differ between the lesional ( approximately 93.9%) and the perilesional normal epidermis ( approximately 92.2 %), indicating that interrupted melanosome transfer occurs in BCE but not in all pigmented epithelial tumors. RT-PCR analysis demonstrated that the expression of PAR-2 mRNA transcripts in basaloid cells is significantly decreased in pigmented BCE compared with the perilesional normal epidermis. In contrast, in pigmented SK, where melanosome transfer to basaloid tumor cells is not interrupted, the expression of PAR-2 mRNA transcripts is comparable between the basaloid tumor cells and the perilesional normal epidermis. Immunohistochemistry demonstrated that basaloid cells in pigmented BCE have less immunostaining for PAR-2 than do keratinocytes in the perilesional normal epidermis whereas in pigmented SK, there is no difference in immunostaining for PAR-2 between the basaloid tumor and the perilesional normal epidermis. These findings suggest that the decreased expression of PAR-2 in the basaloid cells is associated in part with the observed interruption of melanosome transfer in pigmented BCE.

Follicular stem cell carcinoma: histologic, immunohistochemical, ultrastructural, and clinical characterization in 30 dogs.

Diagnostic records of 30 primary and one metastatic follicular stem cell carcinomas in 30 dogs were reviewed. Neoplastic cells had a clear cytoplasm and formed lobules and nests surrounded by a basement membrane. Trichoepitheliomatous and apocrine differentiations were noted in 22 of 30 (73%) and 21 of 30 (70%) primary tumors, respectively. Glycogen was present in 20 of 20 (100%) tumors tested, suggesting tricholemmal differentiation. Antibodies against AE1/AE3 cytokeratin, vimentin, and melanA/MART1 stained 29 of 30 (97%), 29 of 30 (97%), and 12 of 27 (44%) primary tumors, respectively. Small amounts of melanin were identified in 14 primary tumors, either on the hematoxylin and eosin-stained section (n = 6), or on the Fontana-stained section (n = 8 of 14). Ultrastructural features of neoplastic cells included cell junction complexes, swollen mitochondria, neuroendocrine-like granules, and intracytoplasmic non-membrane-bound accumulation of proteinaceous material. Features of this neoplasm are consistent with a follicular stem cell origin. Follow-up information was available for eight dogs. Metastases developed in the draining lymph node at the time of excision of the primary tumor (n = 1) or subsequently (n = 3).

Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.