CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the diagnosis of pilomatrical carcinoma.

BACKGROUND: The Wnt signaling pathway has been implicated in the pathogenesis of pilomatrical tumors. Lymphoid enhancer-binding factor 1 (LEF-1) is a downstream component of this pathway, and Caudal-related homeobox transcription factor 2 (CDX2) has been postulated to regulate it, but little is known about expression of these transcription factors in pilomatrical tumors. METHODS: Immunohistochemistry for CDX2, ß-catenin, LEF-1, CK19, CK5, Special AT-rich sequence- binding protein 2 (SATB2), cadherin 17 and androgen receptor was performed on pilomatricomas (PMs) (N = 12), pilomatrical carcinomas (PMCAs) (N = 12) and non-pilomatrical cutaneous tumors (N = 18). RESULTS: PMs and PMCAs were positive for CDX2 (9/12 PMs, sensitivity = 75%, specificity = 100%; 11/12 PMCAs, sensitivity = 92%, specificity = 100%; P < 0.01), ß-catenin (12/12 PMs, sensitivity = 100%, specificity = 94%; 10/12 PMCAs, sensitivity = 83%, specificity = 94%; P < 0.01) and LEF-1 (12/12 PMs, sensitivity = 100%, specificity = 56%; 12/12 PMCAs, sensitivity = 100%, specificity = 56%; P < 0.01). CDX2 expression was commonly focal, within a discrete subpopulation of squamoid cells. The LEF-1 expression pattern was different and discernable between pilomatrical tumors (strong, diffuse) and non-pilomatrical tumors (weak, patchy). CONCLUSION: This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and this introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as ß-catenin, if not better when taking into account expression pattern, as a diagnostic marker for PMCA, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors.

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.

Pilomatrix Carcinoma: A Benign-Mimic with Malignant Consequences - A Case Report and Review of the Current Literature.

Introduction: Pilomatrix carcinomas (PMXCs) are uncommon, locally aggressive tumors with high recurrence rates, metastatic potential, and fewer than 130 cases reported in the literature. Typically, they present as an unassuming, firm, dermal swelling and therefore are frequently mistaken for more common, benign masses, leading to undertreatment which can cause local invasion and metastatic spread. Diagnosis relies on excision with pathologic analysis; however once diagnosed, there are no current recommendations to guide treatment or surveillance for recurrence or metastases. Case Presentation: Here, we present a case of one of these rare tumors. Our case describes a 1.5 × 2.5 cm firm, mobile mass at the supraorbital rim in an otherwise healthy, young patient. Prior to removal, we suspected a benign pathology; however, excision proved difficult and pathologic diagnosis was consistent with PMXC. Following discussion with tumor board, decision was made to perform Mohs micrographic surgery and staging via CT scans with regular follow-up and surveillance scans. Conclusion: PMXCs are exceedingly rare diagnoses and present like many benign lesions. Therefore, we elected to document this case to encourage providers to keep these biologically aggressive tumors on their list of differential diagnoses in an unsuspecting mass, as well as to provide our own recommendations for treatment and screening for recurrence and metastatic spread.

A Rapidly Growing Forearm Pilomatricoma in an Elderly Patient.

Pilomatricoma is a benign skin tumor of epithelial hair matrix cells that typically presents as a solitary nodule on the head or upper trunk. It occurs most often in children and young adults. While considered uncommon in middle-aged and elderly patients, there are reports of elderly patients with histopathologically diagnosed pilomatricomas; however, these cases primarily occurred on the face. We present a case of an 88-year-old female with a history of non-melanoma skin cancer who presented with a new, rapidly enlarging, biopsy-proven pilomatricoma on the forearm. This case highlights a unique age of onset and location for this skin tumor, suggesting that pilomatricomas are not limited to children and young adults and should be considered in the differential diagnosis of rapidly growing skin lesions in elderly patients. Diagnosis should be confirmed with biopsy in elderly patients, as pilomatricomas may mimic malignant skin lesions.

CDX2 expression in primary skin tumors-case series and review of the literature.

CDX2 expression characterizes tumors of gastrointestinal origin, including those of intestinal-type differentiation. In dermatopathology, CDX2 expression is reported in 4 settings: cutaneous metastases from carcinomas of intestinal origin or differentiation, extramammary Paget's disease associated with an underlying colorectal or urothelial tumor, pilomatricomas and pilomatrical carcinomas, and rare primary cutaneous (adeno)squamous carcinomas with intestinal immunophenotype. Over 4 years (10/2017-10/2021), 252 dermatopathology cases with CDX2 immunostain were reviewed, revealing 46 cases with confirmed positive staining. Among them, 11 cases confirmed as primary nonintestinal type cutaneous carcinoma with definitively positive CDX2 nuclear staining were further studied. All cases demonstrated basaloid morphology with atypia, variable necrosis, and brisk mitotic activity. Cases 1-5 had heterogeneous features that cannot be further classified, including 2 cases with neuroendocrine or pseudoglandular/pseudopapillary features, and 1 case with human papillomavirus high-risk E6/E7 ISH positivity. In cases 6 through 11, the diagnosis of pilomatrical carcinoma was supported morphologically. This study substantiates the association of CDX2 with pilomatrical carcinoma. In addition, CDX2 positivity was observed in a subset of basaloid cutaneous carcinomas of ambiguous classification. However, this finding also raises a diagnostic pitfall in clinical diagnostic specificity of the CDX2 immunostain in skin cancers, which can be observed in rare while heterogeneous subsets of primary cutaneous carcinomas with primitive cytomorphology.

Common sense and tumor treatment. A case of pilomatrical carcinoma in a 21-year-old patient with surprisingly rapid tumor progression.

Pilomatrical carcinoma is a rare tumor originating from skin appendages, usually occurring between the 5th and 7th decade of life. We present a case of an exceptionally young, 21-year-old patient with surprisingly rapid tumor progression and answer the question, what was the reason for such uncontrolled tumor growth. The main concern is the diagnostic challenge and a peculiar, one week race against time and tumor progression so that the least disfiguring surgery could be done.