Wnt/ß-Catenin-Activated Nonpilomatrical Carcinoma of the Skin: A Case Series.

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/ß-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/ß-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/ß-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear ß-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and ß-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/ß-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

Malignant Melanocytic Matricoma: A Rare Skin Tumor That Can Clinically Mimic Melanoma.

Malignant melanocytic matricoma (MMM) is an extremely rare skin malignant neoplasm composed of epithelial cells with matrical differentiation and dendritic melanocytes. We found only 11 cases reported in the literature to date according to the databases consulted (PubMed/Medline, Scopus, and Web of Science). Here, we report a case of MMM in an 86-year-old woman. A histological examination showed a dermal tumor with a deep infiltrative pattern, without an epidermal connection. On immunohistochemical staining, tumor cells were positive for cytokeratin AE1/AE3, p63, and beta-catenin (nuclear and cytoplasmic staining) and negative for HMB45, Melan-A, S-100 protein, and androgen receptor. Melanic antibodies highlighted scattered dendritic melanocytes in tumor sheets. The findings did not support the diagnosis of melanoma, poorly differentiated sebaceous carcinoma, and basal cell carcinoma, but supported the diagnosis of MMM.

Bowen disease with matrical differentiation: Report of an exceptional histopathologic presentation.

Matrical differentiation is the distinctive feature of pilomatricoma and other purely matrical adnexal neoplasms; additionally, foci of matrical differentiation have been also described in hybrid cysts of Gardner syndrome, as well as in a wide variety of benign and malignant cutaneous tumors, including basal cell carcinoma. We report an exceptional case of Bowen disease exhibiting multiple foci of matrical differentiation, as confirmed by means of immunohistochemical studies. Several types of divergent, non-squamous differentiation have been exceptionally reported in cutaneous squamous cell carcinoma in situ (cSCCIS), including sebaceous, mucinous/glandular, poroid, tricholemmal, and neuroendocrine differentiation; matrical differentiation may be added to this list. Our findings further emphasize the undifferentiated nature of neoplastic cells in cSCCIS.

Salivary ghost cell carcinoma: case report and proposal of a new entity.

Various topographically heterogeneous, histologically related groups of basaloid tumours are characterized by ghost cell differentiation with associated CTNNB1 mutations and nuclear ß-catenin expression. We describe the unique case of a malignant tumour with ghost cell differentiation in the floor of the mouth, in which clinical, radiological, histological, immunohistological and molecular data altogether strongly indicate classification as a new type of salivary gland carcinoma.

Giant proliferating pilomatricoma; report of a rare entity.

Proliferating pilomatricoma is a benign tumour and a rare variant of pilomatricoma that has the potential for local recurrence if incompletely excised. We report a case of giant proliferating pilomatricoma on the forearm of a 66-year-old woman. This tumour was unusually large and the presence of ulceration and rapid growth raised clinical suspicion of malignancy. The identification of shadow or ghost cells is a good clue to matrical differentiation, which can be confirmed by ß-catenin immunostaining.

Nasal Basal Cell Carcinoma with Matrical Differentiation: Risk of Metastasis and Impact on Management.

Basal cell carcinoma (BCC) is the most common type of skin cancer. Microscopically, BCC can be classified into indolent-growth and aggressive-growth subtypes. Additionally, uncommon variants have been described in the literature including adamantinoid, granular, clear cell, and BCC with matrical differentiation (BCCMD). If left untreated, BCC can invade locally causing significant tissue destruction while metastatic BCC is extremely rare. There have only been rare cases of BCCMD previously reported in the literature with none exhibiting metastasis. In this report, a 76 year old male patient presented to our center with a recurrent nasal lesion. He had been diagnosed with BCC at another institution about 8 years prior. He underwent a completion rhinectomy procedure, and on microscopic examination the tumor was diagnosed as BCCMD. In view of the uncommon pathology, a PET scan was ordered, which showed a left submandibular hypermetabolic lymph node with central areas of necrosis. A fine needle aspirate from the node confirmed metastasis, and the patient underwent subsequent neck dissection. In conclusion, we have presented a very rare case of a nasal BCCMD with regional metastasis. To the best of our knowledge, this constitutes the first reported case in the English literature. This might raise the possibility of a probable metastatic potential for this lesion and subsequently a more aggressive behavior. However, it is to be noted that this is a single case report and the affirmation of any metastatic potential would still need to be confirmed through additional future reports.

[Basal cell carcinoma with matrical differentiation]. / Carcinome basocellulaire à différenciation matricielle.

Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis.

Pilomatrix carcinoma: 13 new cases and review of the literature with emphasis on predictors of metastasis.

BACKGROUND: Pilomatrix carcinoma is a rare cutaneous tumor derived from follicular matrix cells with few cases documented in the literature. OBJECTIVE: We sought to better characterize this tumor by analyzing its epidemiologic, clinical, and histopathologic features in 13 new cases and by reviewing the literature. METHODS: All cases of pilomatrix carcinoma from a large regional dermatopathology practice were identified and analyzed by chart review for clinical and histopathologic characteristics. Similar characteristics were compiled from an additional 123 cases in the English-language literature. Cox proportional hazards regression models were used to determine risk factors associated with the development of metastasis for all identified metastatic tumors. RESULTS: Our 13 tumors were most common in middle-aged to older white men and presented mostly on the head/neck. Histopathologically, tumors were asymmetric, were poorly circumscribed, were composed of basaloid and "ghost" cells, had frequent atypical mitoses, and had infrequent lymphovascular invasion. Wide excision was considered the most definitive treatment modality, but local recurrence was common. When analyzing all reported cases of metastasis using statistics, metastasis was significantly associated (hazard ratio 3.45, P < .0413) with local tumor recurrence. LIMITATIONS: The retrospective, single-center design and the reliance on electronic medical records are limitations. CONCLUSIONS: This study helps better characterize pilomatrix carcinoma and identifies potential predictors of metastasis.

Melanocytic matricoma: two cases of a rare entity in women.

Melanocytic matricoma is a rare cutaneous adnexal tumor occurring in humans with only 13 cases reported in the literature. The typical lesion is a circumscribed pigmented nodule on sun-damaged skin. Most cases have occurred in elderly men. The tumor contains a mixed population of matrical cells, supramatrical cells, shadow or ghost cells, and dendritic melanocytes. We report two cases of melanocytic matricoma in two elderly women with unusual histopathological features such as cystic degeneration and focal granulomatous inflammation, which are considered to be atypical for this entity.

Skin tumors with matrical differentiation: lessons from hair keratins, beta-catenin and PHLDA-1 expression.

BACKGROUND: Pilomatricomas are tumors that emulate the differentiation of matrix cells of the hair follicle, showing cortical differentiation, with sequential expression of K35 and K31 keratins. Beta-catenin gene is frequently mutated in pilomatricoma, leading to beta-catenin nuclear accumulation, and to downstream expression of LEF1. Skin matrical tumors other than pilomatricoma are very rare, and comprise purely matrical tumors and focally matrical tumors. We aimed at studying cortical differentiation, beta-catenin pathway and expression of the follicular stem-cell marker PHLDA1 in a series of matrical tumors other than pilomatricoma. METHODS: In 36 prospectively collected tumors, K31, K35, CK17, LEF1, HOXC13, beta-catenin and PHLDA1 expressions were evaluated. Five pilomatricomas were used as controls. RESULTS: In 18 purely matrical tumors (11 matrical carcinomas, 4 melanocytic matricomas, 3 matricomas) and 18 focally matrical tumors (11 basal cell carcinomas, 3 trichoepithelioma/trichoblastomas, 4 others), sequential K35, HOXC13 and K31 expressions were found, indicating cortical differentiation. Germinative matrix cells were always CK17-, and showed nuclear beta-catenin accumulation, with LEF1 and PHLDA1 expressions. CONCLUSIONS: Nuclear beta-catenin and LEF1 expression was highly conserved in matrical tumors, and suggested a common tumorigenesis driven by Wnt pathway activation. PHLDA1 was consistently expressed in matrical tumors and in areas of matrical differentiation.