Tricholemmal Differentiation Research Articles

Cutaneous tricholemmal carcinoma: a 15-year single center experience.

Background Clear cell morphology has been described in several cutaneous neoplasms either as a specific feature of some entities either as a morphological variant in the spectrum, and these two entities are frequently considered together in the differential diagnosis. Methods We reviewed our series of cases occurred in our laboratory in order to further quantify the number of cases showing morphological features of tricholemmal differentiation and to investigate other clinical or histological difference. We retrieved 91 cases and, for each of them, all the clinical data regarding age, sex, clinical features, and clinical suspicious were collected, when available. Results The revision of the specimens concluded with a final diagnosis of tricholemmal carcinoma in 15 cases (17%), all the other cases were thus considered as squamous cell carcinoma with clear cell features. No statistically significant correlations were observed with the demografic or clinicopatholagical parameters such as age, sex or dimensions, but morphological revision highlighted a potentially greater vertical growth frequently not matched by a concomitant radial one in tricholemmal carcinoma than in squamous tumors. Conclusions The debate upon the diagnostic distinction of these tumors is still ongoing with authors proposing the tricholemmal carcinoma as a variant of a squamous cell carcinoma rather than a distinct entity. Further studies are needed to confirm our data and to evaluate the reproducibility of this feature.

Skin tumors in xeroderma pigmentosum: Evaluation of a large series and a literature review

Xeroderma pigmentosum (XP) is a rare genodermatosis with a lifelong propensity to develop malignant skin tumors. In this retrospective study, 24 XP patients were evaluated with regard to frequency and clinicopathological features of benign and malignant skin tumors. Seventeen patients had at least one malignant skin tumor diagnosed: basal cell carcinoma (BCC) in 13 patients (n=72), basosquamous carcinoma in three patients (n=4), squamous cell carcinoma in six patients (n=13), keratoacanthoma in three patients (n=15), and melanoma in six patients (n=18). Most melanomas (n=15) were in situ lesions. Several benign skin tumors were noted such as tricholemmoma (n=1), trichoepithelioma (n=1), trichoblastoma (n=1), follicular infundibulum tumor (n=1), keratoacanthoma-like follicular lesion (n=1), adnexal tumors with folliculosebaceous (n=1) and tricholemmal differentiation (n=1), and neurofibroma (n=1). Benign vascular proliferations including pyogenic granulomas (n=8), widespread telangiectasias, and senile angioma-like lesions were also observed in 3, 5, and 5 patients, respectively. Similar to many reports, BCC was found to be the most common malignant skin tumor. The high prevalence of benign adnexal tumors of follicular differentiation, some of them showing mixed histopathological features and various vascular proliferations in our series raises the question of whether they indicate a formerly undescribed association with XP.

Cutaneous tricholemmal carcinoma: a 15-year single center experience.

Clear cell morphology has been described in several cutaneous neoplasms either as a specific feature of some entities either as a morphological variant in the spectrum, and these two entities are frequently considered together in the differential diagnosis. We reviewed our series of cases occurred in our laboratory in order to further quantify the number of cases showing morphological features of tricholemmal differentiation and to investigate other clinical or histological difference. We retrieved 91 cases and, for each of them, all the clinical data regarding age, sex, clinical features, and clinical suspicious were collected, when available. The revision of the specimens concluded with a final diagnosis of tricholemmal carcinoma in 15 cases (17%), all the other cases were thus considered as squamous cell carcinoma with clear cell features. No statistically significant correlations were observed with the demografic or clinicopatholagical parameters such as age, sex or dimensions, but morphological revision highlighted a potentially greater "vertical" growth frequently not matched by a concomitant radial one in tricholemmal carcinoma than in squamous tumors. The debate upon the diagnostic distinction of these tumors is still ongoing with authors proposing the tricholemmal carcinoma as a variant of a squamous cell carcinoma rather than a distinct entity. Further studies are needed to confirm our data and to evaluate the reproducibility of this feature.

Cystic Tricholemmal Carcinoma In Situ

An 89-year-old man presented with a clinically cystic 4-mm papule on the left temple. The clinical impression was a benign cyst. Pathologic examination revealed a small, symmetric-appearing, well-circumscribed, dermal-based cystic lesion with markedly atypical-appearing clear to squamoid cells lining the cyst wall, consistent with carcinoma in situ involving the cyst. The cells showed abundant glycogen-containing cytoplasm (confirmed by Periodic acid Schiff stains with and without diastase), consistent with tricholemmal differentiation, and areas of tricholemmal/pilar-type keratinization (without a granular layer), consistent with tricholemmal carcinoma in situ, most likely arising in a tricholemmal/pilar cyst. Ki-67 and p53 immunohistochemical stains were strongly positive (with more than 20% of nuclei staining on Ki-67 and more than 80% on p53) in the cyst-lining cells, further supporting the interpretation of carcinoma in situ. Multiple deeper level sections were examined but did not show any evidence of an associated invasive carcinoma. Tricholemmal (pilar) cysts are common benign adnexal lesions and atypia/dysplasia or carcinoma in situ arising within them is exceedingly rare. Previously, only one case of a tricholemmal cyst with carcinoma in situ has been reported. That case was associated with an atypical fibroxanthoma. We report only the second case of tricholemmal carcinoma in situ, most likely involving a tricholemmal cyst, which was not associated with another tumor or evidence of invasive carcinoma.

Folliculocentric squamous cell carcinoma with tricholemmal differentiation: a reappraisal of tricholemmal carcinoma

The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC.

Tricholemmoma and Clear Cell Squamous Cell Carcinoma (Associated With Bowen's Disease)

There have been only a few reported comparative immunohistochemical studies of normal hair follicles and tricholemmomas. Clear cell squamous cell carcinomas (SCCs), which are derived from Bowen's disease, histopathologically mimic or are difficult to distinguish from tricholemmal carcinoma. The purpose of and methods used in the present study are as follows: (1) evaluation of whether the immunohistochemical profile (cytokeratin (CK)1, CK10, CK17, CD34, and D2-40) in normal hair follicles is retained in tricholemmomas (11 lesions); and (2) a study of the immunohistochemical profile of in situ or superficially invasive clear cell SCCs (associated with Bowen's disease) (10 lesions) to investigate the presence or absence of tricholemmal differentiation markers in these lesions. The present study demonstrated that (1) the immunohistochemical profile of the normal outer root sheath cells was generally retained in tricholemmomas; (2) in contrast to the D2-40 expression in tricholemmomas (only a peripheral pattern, which is similar to that in the normal outer root sheath), the CD34 expression in tricholemmomas represented in a diffuse pattern, a peripheral pattern, and a combined diffuse and peripheral pattern; (3) tricholemmomas are benign neoplasms with outer root sheath (below the isthmus) differentiation, which characteristically show upregulation of CD34 expression with some functionally similar conditions to the terminal hair follicles in the anagen phase; and (4) there is no clear immunohistochemical evidence of tricholemmal differentiation in clear cell SCC (associated with Bowen's disease).

Cutaneous Adnexal Differentiation and Stromal Metaplasia in Palate Pleomorphic Adenomas: A Potential Diagnostic Pitfall That May Be Mistaken for Malignancy

Cutaneous adnexal differentiation is well-recognized in benign mixed tumors occurring in cutaneous sites. The incidence of this histologic finding in salivary gland sites is not known. We sought to describe the incidence of cutaneous adnexal differentiation in benign mixed tumors of the palate, lip, and parotid gland. Benign mixed tumors of the palate (n=30), lip (n=13), and parotid gland (n=37) resected between 1980 and 2009 at a single academic medical institution were reviewed. All hematoxylin and eosin-stained sections containing neoplasm were reviewed by all authors including one dermatopathologist (S.H.O.). After confirming the diagnosis of benign mixed tumor, we evaluated for morphologic evidence of cutaneous adnexal differentiation and metaplastic epithelial and stromal changes. Chart review was conducted to obtain pertinent clinical information. Cutaneous adnexal differentiation was seen in 20% of palate and 39% of lip benign mixed tumors but in no parotid tumors. The most frequent features of cutaneous adnexal differentiation were tricholemmal differentiation (20% of palate and 39% of lip tumors), infundibulocystic structures (17% and 31%), and trichohyalin granules (13% and 31%). Sebaceous differentiation was seen in only one palate tumor. Varying amounts of stromal adipose were seen in 62, 37, and 22% of lip, palate, and parotid tumors. Osseous metaplasia was seen in one tumor from each site. When cutaneous adnexal differentiation occurs in salivary gland pleomorphic adenomas, it can present a diagnostic pitfall that must not be misinterpreted as carcinoma at biopsy, fine needle aspiration, or frozen section.

Squamous Cell Carcinoma With Clear Cells: How Often is There Evidence of Tricholemmal Differentiation?

Clear-cell carcinoma of the skin was described by Kuo in 1980 as a cutaneous tumor composed of clear cells that lacked cytoplasmic glycogen or evidence of tricholemmal keratinization. Tricholemmal carcinoma (TC) is conventionally considered to be a neoplasm derived from adnexal keratinocytes with glycogenated clear cells and evidence of outer root sheath or tricholemmal differentiation. The existence of TC has been questioned as it has been argued that without clear immunohistochemical evidence of outer root sheath differentiation, TC cannot be distinguished from clear-cell carcinoma of the skin. Our laboratory has not routinely stained the cases that appear to be carcinomas with clear keratinocytes to determine if glycogen is present and has not made the diagnosis of TC. We sought to test whether the presence of glycogen, light microscopic features said to be typical of TC, or immunohistochemical findings would delineate a group of "true" TC among the cases that we have been recording as squamous cell carcinomas with clear cells (SCC-C). 40 cases of SCC-C were evaluated for 7 histologic and histochemical criteria (a lobular arrangement, peripheral palisading, tricholemmal keratinization, folliculocentricity, evidence of a preexisting tricholemmoma, the presence of intracytoplasmic glycogen, and a thickened basement membrane) said to characterize TC. Selected cases were then stained for immunohistochemical markers (CD34, CK17, and NGFR/p75) that have been used as evidence for tricholemmal differentiation in some studies. Of the 40 cases, 38 (95%) SCC-C showed intracytoplasmic glycogen (periodic Schiff positivity abolished by diastase) and 55% of cases showed foci of tricholemmal keratinization. Overall, the carcinomas showed a spectrum of the above aggregated criteria ranging from 0 to 5. None possessed all the criteria expected in an ideal TC. In addition, the majority of the selected SCC-C in this study were negative (85%) for antigens typically found in the outer root sheath epithelium of the hair follicle. The glycogen-free clear-cell carcinoma described by Kuo seems uncommon in our patient population. Rare cases of SCC-C met the majority of Headington's criteria for TC or showed immunohistochemical evidence of tricholemmal differentiation. Thus, we also conclude that well-differentiated TC is rare and its description in the literature may overstate the case that it is a well-characterized cutaneous neoplasm.

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).

Perturbation in connexin 43 and connexin 26 gap‐junction expression in mouse skin hyperplasia and neoplasia

To examine the possible role of gap junctions in mouse skin tumor progression, we generated a panel of mouse skin tissue samples exhibiting normal, hyperplastic, or neoplastic changes and characterized the expression of the gap-junction genes connexin 43 (Cx43) and connexin 26 (Cx26) by in situ hybridization and immunohistochemical analyses. In normal skin, these two gap junction genes were differentially expressed; Cx43 was found predominantly in the less differentiated lower spinous layers, whereas Cx26 was found in terminally differentiating upper spinous and granular layers. In hyperplastic epidermis exhibiting an expansion of the differentiated upper layer, i.e., epidermis with a thickened granular layer or in which the granular layer was replaced with keratinocytes exhibiting tricholemmal differentiation, expression of Cx43 and Cx26 remained segregated in the lower and upper spinous layers, respectively. However, in papillomas, Cx26 was localized in the lower but not upper spinous layer, an expression pattern identical to that of Cx43. In addition, the overall expression levels of both Cx43 and Cx26 appeared to be greatly elevated in the papillomas. It is interesting that such marked alteration in the pattern of Cx26 expression occurred within the context of hyperplastic changes histologically identical to those seen in the nonpapillomous hyperplasias. Interestingly, in neoplastic skin lesions containing a squamous cell carcinoma, Cx43 and Cx26 expression was extinguished. Moreover, expression of Cx43 was also significantly reduced in adjacent apparently nonneoplastic tissues. Overall, these observations show that perturbations in gap-junction gene expression are associated with skin hyperplasia and neoplasia. Such findings suggest a possible role for gap junctions in the malignant conversion of mouse epidermal cells. © 1996 Wiley-Liss, Inc.

Perturbation in connexin 43 and connexin 26 gap-junction expression in mouse skin hyperplasia and neoplasia

To examine the possible role of gap junctions in mouse skin tumor progression, we generated a panel of mouse skin tissue samples exhibiting normal, hyperplastic, or neoplastic changes and characterized the expression of the gap-junction genes connexin 43 (Cx43) and connexin 26 (Cx26) by in situ hybridization and immunohistochemical analyses. In normal skin, these two gap junction genes were differentially expressed; Cx43 was found predominantly in the less differentiated lower spinous layers, whereas Cx26 was found in terminally differentiating upper spinous and granular layers. In hyperplastic epidermis exhibiting an expansion of the differentiated upper layer, i.e., epidermis with a thickened granular layer or in which the granular layer was replaced with keratinocytes exhibiting tricholemmal differentiation, expression of Cx43 and Cx26 remained segregated in the lower and upper spinous layers, respectively. However, in papillomas, Cx26 was localized in the lower but not upper spinous layer, an expression pattern identical to that of Cx43. In addition, the overall expression levels of both Cx43 and Cx26 appeared to be greatly elevated in the papillomas. It is interesting that such marked alteration in the pattern of Cx26 expression occurred within the context of hyperplastic changes histologically identical to those seen in the nonpapillomous hyperplasias. Interestingly, in neoplastic skin lesions containing a squamous cell carcinoma, Cx43 and Cx26 expression was extinguished. Moreover, expression of Cx43 was also significantly reduced in adjacent apparently nonneoplastic tissues. Overall, these observations show that perturbations in gap-junction gene expression are associated with skin hyperplasia and neoplasia. Such findings suggest a possible role for gap junctions in the malignant conversion of mouse epidermal cells.

Clear cell basal cell carcinoma: An unusual degenerative variant

Clear cell basal cell carcinoma (BCC) is an unusual variant of BCC which is characterized by a variable component of large clear cells. Twenty cases are presented which are further subdivided into pure, mixed, or metatypical categories. Although initially thought to represent sebaceous or tricholemmal differentiation, electron microscopic studies demonstrated that the clear cell changes are a degenerative phenomenon, probably involving lysosomes.

Verruca vulgaris with tricholemmal differentiation

Verruca vulgaris with tricholemmal differentiation