Fibroepithelioma of Pinkus is a true basal cell carcinoma developing in association with a newly identified tumour-specific type of epidermal hyperplasia.

BACKGROUND: Fibroepithelioma of Pinkus (FEP) has long been viewed as a subtype of basal cell carcinoma (BCC). Recently, however, the proposal has been made that FEP represents a fenestrated trichoblastoma/trichoepithelioma. One of the main arguments is the presence of Merkel cells in FEP, which typically do not occur in BCC. OBJECTIVES: As the new stem cell marker, PHLDA1 (TDAG51), labels trichoepithelioma but not BCC, our aim was to characterize its staining pattern in FEP. Because adnexal tumours have been viewed as recapitulating embryogenesis, we also examined PHLDA1 immunoreactivity in the skin of human embryos and fetuses. METHODS: We studied immunohistochemically PHLDA1 staining in 31 FEPs, 14 BCCs and 16 trichoepitheliomas and compared this with its staining pattern in embryonic skin and with the distribution of Merkel cells. RESULTS: In FEP, PHLDA1 labels the anastomosing network of thin cellular strands but not the basaloid nubbins. During embryogenesis, PHLDA1 stains the basal cell layer of the epidermis, as long as adnexal structures develop. Immunoreactivity for PHLDA1 correlates positively with the presence of Merkel cells. CONCLUSIONS: We propose that the thin anastomosing network of PHLDA1-positive cells represents a type of epidermal hyperplasia specific to FEP. The multifocal BCCs that are PHLDA1-negative develop from this network which becomes incorporated into the tumour. Viewing the anastomosing network as a tumour-specific form of epidermal hyperplasia explains the hitherto enigmatic presence of Merkel cells in FEP.

p75 Neurotrophin receptor differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma: insights into the histogenesis of adnexal tumours based on embryology and hair follicle biology.

BACKGROUND: Tumour development is frequently described in the basic pathology literature as a recapitulation of embryogenesis. However, a link between the embryology of the skin and the histogenesis of adnexal tumours has been largely overlooked. The low-affinity p75 neurotrophin receptor (p75NTR) has a profound role in hair follicle biology. We therefore speculated that it is involved in the histogenesis of follicular adnexal tumours. One of the most challenging diagnoses in dermatopathology is differentiating morphoeic basal cell carcinoma from desmoplastic trichoepithelioma. OBJECTIVES: To describe the expression pattern of p75NTR during cutaneous embryogenesis, in the adult hair follicle and in morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. METHODS: Evaluation of the staining pattern for p75NTR was performed using standard immunohistochemical techniques. For comparison, we examined staining for cytokeratin 20 which highlights Merkel cells. RESULTS: All 17 desmoplastic trichoepitheliomas were immunoreactive with > 80% of the cells stained, whereas 12 of the 14 (86%) morphoeic basal cell carcinomas were p75NTR negative. In the two positive cases of morphoeic basal cell carcinoma < 30% of cells were labelled. In the late bulbous hair peg stage and in the postnatal anagen hair follicle p75NTR highlights the outer root sheath. CONCLUSIONS: Our results support the classification of desmoplastic trichoepithelioma as a follicular hamartoma mimicking the outer root sheath. In contrast, the lack of p75NTR expression in morphoeic basal cell carcinoma favours a concept of this tumour as a more primitive follicular lesion with the characteristics of a carcinoma and not a hamartoma. We suggest including p75NTR as a tool in the differential diagnosis between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma.

Correlation of embryonic fusion planes with the anatomical distribution of basal cell carcinoma.

BACKGROUND: The clinical relevance of the anatomic distribution of basal cell carcinoma is not completely understood. Embryonic fusion planes--the regions of mesenchymal migration and fusion of the five primordial facial processes during the 5th to 10th weeks of human development--have been implicated in the pathogenesis of basal cell carcinoma. OBJECTIVE: This study sought to examine the predilection of midfacial basal cell carcinoma for cutaneous anatomical sites correlated to embryonic fusion planes. METHODS AND MATERIALS: Using archived digital images and a detailed anatomic diagram, cases of basal cell carcinoma were coded according to their specific location and were aggregated into two anatomic domains according to their correlation to embryonic fusion planes. The relative tumor densities were calculated. RESULTS: Of the 1,457 cases examined, 859 were located in the midface. Thirty-five percent of the midfacial lesions were located on the domain correlated to embryonic fusion planes, which represented 11.3% of the total surface area of the midface. The relative tumor density of lesions in the fusion plane domain was 3.06 compared to 0.74 for the remaining lesions (p< .001). CONCLUSIONS: Although there is no consensus about the importance of anatomic location in the pathogenesis of basal cell carcinoma, these data indicate that, after adjusting for surface area, basal cell carcinoma was more than four times more likely to occur on an embryonic fusion plane than on other regions of the midface. These data support the possibility of an embryologic role for the pathogenesis of basal cell carcinoma.

Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours.

Sporadic basal cell carcinoma (BCC) is the most common type of malignant cancer in fair-skinned adults. Familial BCCs and a fraction of sporadic BCCs have lost the function of Patched (Ptc), a Sonic hedgehog (Shh) receptor that acts negatively on this signalling pathway. Overexpression of Shh can induce BCCs in mice. Here we show that ectopic expression of the zinc-finger transcription factor Gli1 in the embryonic frog epidermis results in the development of tumours that express endogenous Gli1. We also show that Shh and the Gli genes are normally expressed in hair follicles, and that human sporadic BCCs consistently express Gli1 but not Shh or Gli3. Because Gli1, but not Gli3, acts as a target and mediator of Shh signalling, our results suggest that expression of Gli1 in basal cells induces BCC formation. Moreover, loss of Ptc or overexpression of Shh cannot be the sole causes of Gli1 induction and sporadic BCC formation, as they do not occur consistently. Thus any mutations leading to the expression of Gli1 in basal cells are predicted to induce BCC formation.

Influence of embryonal fusion lines for recurrence of basal cell carcinomas in the head and neck.

A reinvestigation of 171 basal cell carcinomas of the head and neck treated by surgical excision revealed 23 recurrences. Recurrence rate in one group of basal cell carcinomas, situated on embryologic fusion lines, was statistically higher than in other groups of basal cell carcinomas situated on other parts of the face and on the capillitium which served as control. Histopathologic subclassification of the recurrent basal cell carcinomas revealed a higher incidence of nodular type with infiltrative margin and of the infiltrative type. Basal cell carcinomas situated in fusion lines tended to grow deeper than in other sites. It was concluded that embryologic fusion lines in the face provide risk zones for spread and recurrence of basal cell carcinomas. Subclassification of basal cell carcinomas should be performed in the routine histopathologic reporting of these neoplasms as a means of predicting recurrence.