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Background

Trichoepitheliomas are hamartomas arising from hair follicular epithelium. They have a characteristic intimate association of the epithelium and mesenchyme. The characteristic structure, under the microscope, the papillary-mesenchymal body. This is a recapitulation of a primitive hair bulb. It is benign but must be distinguished from a basal cell carcinoma.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS Epithelioma adenoides cysticum

 

DISEASE ASSOCIATIONS CHARACTERIZATION
ALOPECIA AND MYASTHENIA GRAVIS  

Generalized trichoepitheliomas with alopecia and myasthenia gravis: clinicopathologic and immunohistochemical study and comparison with classic and desmoplastic trichoepithelioma.

Starink TM, Lane EB, Meijer CJ.

J Am Acad Dermatol 1986 Nov;15(5 Pt 2):1104-12 Abstract quote

We report on a patient with a syndrome characterized by smooth facial papules and nodules; alopecia of the eyebrows, eyelashes, and most body hair; mild alopecia of scalp hair; possibly hypohidrosis; and myasthenia gravis.

The clinical, histologic, and immunohistochemical findings are compared with classic and desmoplastic trichoepitheliomas. All fourteen biopsy specimens of the patient showed a lacelike network of basaloid cells with follicular differentiation and a prominent stroma with focal alkaline phosphatase activity, as in fourteen comparison specimens of classic trichoepithelioma. Studies with antikeratin antibodies of various specificities also revealed similar patterns. The tumor cells showed a keratin phenotype characteristic of cells of the infrainfundibular outer root sheath, that is, positive staining with basal keratinocyte markers, negative staining with suprabasal keratinocyte markers, and patchy staining with LP2K (against keratin 19). beta 2-Microglobulin expression was partially or totally absent.

It is concluded that the lesions in our patient actually are trichoepitheliomas. The condition may represent a new syndrome that either is closely related to the generalized hair follicle hamartoma (basaloid follicular hamartoma) or is a variant. The finding of generalized trichoepitheliomas with clinical and microscopic alopecia should alert one to the possibility of myasthenia gravis.

 

PATHOGENESIS CHARACTERIZATION

The gene for multiple familial trichoepithelioma maps to chromosome 9p21.

Harada H, Hashimoto K, Ko MS.

Department of Dermatology and Syphilology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

J Invest Dermatol 1996 Jul;107(1):41-3 Abstract quote

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small tumors predominantly on the face. To map the causative gene, we performed linkage analysis with microsatellite markers in three American families. We found a significant linkage of a gene for MFT to chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0. The disease locus was defined to a 4-cM region between IFNA and D9S126.

Because several tumor suppressor genes including p16 and p15 have been mapped to this region, the gene for MFT may also be a tumor suppressor.

Sporadic trichoepithelioma demonstrates deletions at 9q22.3.

Matt D, Xin H, Vortmeyer AO, Zhuang Z, Burg G, Boni R.

Department of Dermatology, University Hospital of Zurich, Switzerland.

Arch Dermatol 2000 May;136(5):657-60 Abstract quote

BACKGROUND: Trichoepithelioma (TE) is a benign cutaneous tumor that originates from hair follicles and occurs either in multiple or solitary lesions. Multiple TE is transmitted as an autosomal dominant trait, and a region at 9p21 is thought to be involved in the tumorigenesis. Solitary TE occurs more commonly than multiple TE and is not inherited. Histologically, TE tumors contain horn cysts and abortive hair papillae. A basal cell carcinoma appearance in some or all regions of a TE tumor can happen. In sporadic basal cell carcinoma, frequent deletions at 9q22.3 (Drosophila patched gene) have occurred. The objective of this study is to test whether loss of heterozygosity (LOH) on either 9p21 or on chromosome 9q22.3 could be detected in archival sporadic TE.

OBSERVATIONS: We studied 29 randomly selected cases of sporadic TE by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed tissue specimens on glass slides. Analysis was performed with the polymorphic markers IFNA and D9S171 (9p21) as well as D9S15, D9S303, D9S287, and D9S252 (9q22.3).

RESULTS: The LOH at 9q22.3 was identified in 14 (48%) of 29 cases with at least 1 marker, while LOH could not be demonstrated using the markers IFNA and D9S171 (9p21).

CONCLUSIONS: The results show that the Drosophila patched gene LOH can be frequently identified in paraffin-embedded sporadic TE after routine processing and indicates a common gatekeeper mechanism for both TE and basal cell carcinoma.

 

GROSS APPEARANCE/
CLINICAL
VARIANTS
CHARACTERIZATION
General  
VARIANTS  
FAMILIAL  

Solitary familial desmoplastic trichoepithelioma. A study by conventional and electron microscopy.

Dervan PA, O'Hegarty M, O'Loughlin S, Corrigan T.

Am J Dermatopathol 1985 Jun;7(3):277-82 Abstract quote

Solitary desmoplastic trichoepitheliomas from a mother and two daughters were studied by conventional and electron microscopy.

Differential diagnosis by conventional microscopy is briefly discussed. The lesions consisted of cords and nests of basaloid cells set in fibrotic stroma and confined to the dermis. In addition, each lesion contained horn cysts and focal areas of calcification. Horn cysts were occasionally identified in continuity with infundibulae of normal hair follicles. Semithin sections showed cords and nests of cells in continuity with the horn cysts. Ultrastructurally, a continuous basal lamina surrounded the cords of basaloid cells and connected to horn cysts. Individual cells contained tonofilaments and were attached to adjacent cells by desmosomes. Hemidesmosomes were present at peripheral cell membranes bounded by basal lamina. There was no glandular differentiation.

Our observations by electron and conventional microscopy support a conclusion that desmoplastic trichoepitheliomas are derived from hair appendages.


Multiple familial trichoepitheliomas: a folliculosebaceous-apocrine genodermatosis.

Clarke J, Ioffreda M, Helm KF.

Am J Dermatopathol 2002 Oct;24(5):402-5 Abstract quote

We reviewed the pathologic findings on a family with multiple hereditary trichoepitheliomas. Although the majority of the lesions were trichoepitheliomas, basal cell carcinomas, spiradenomas, and spiradenomas with cylindromatous foci (spiradenocylindroma) were present, representing a spectrum of lesions exhibiting folliculosebaceous (trichoepithelioma, basal cell carcinoma) and apocrine (spiradenoma, spiradenocylindroma) differentiation.

Multiple familial trichoepitheliomas may be a syndrome whereby tumors develop from undifferentiated germinative cells of the folliculosebaceous-apocrine unit. Published findings regarding the genetics of this syndrome and solitary trichoepitheliomas are reviewed; although the molecular basis for the tumors has yet to be determined, current data suggest that a tumor suppressor gene may be involved.

VULVA  

Trichoepithelioma of the vulva. A report of two cases.

Cho D, Woodruff JD.

Department of Gynecology and Obstetrics, Johns Hopkins Hospital, Baltimore, Maryland

J Reprod Med 1988 Mar;33(3):317-9 Abstract quote

Trichoepithelioma usually presents clinically as single or multiple nodules on the face, scalp, neck and trunk, and no cases of it on the vulva have been described before. Vulvar trichoepithelioma has complex histologic patterns and originates in appendages that simulate malignancy.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  

Papillary mesenchymal bodies: a histologic finding useful in differentiating trichoepitheliomas from basal cell carcinomas.

Brooke JD, Fitzpatrick JE, Golitz LE.

Department of Pathology, Fitzsimons Army Medical Center, Aurora, CO 80045-5000.

J Am Acad Dermatol 1989 Sep;21(3 Pt 1):523-8 Abstract quote

To distinguish a basal cell carcinoma (BCC) from a trichoepithelioma can be difficult even for an experienced dermatopathologist. Previously reported differentiating histologic features are relative criteria that may be shared by both tumors.

In a review of 30 consecutive cases each of trichoepitheliomas, keratotic BCC, and routine BCC, classic criteria were compared with papillary mesenchymal body formation. Papillary mesenchymal bodies are distinct fibroblastic aggregations that represent abortive attempts to form the papillary mesenchyme responsible for hair induction. Papillary mesenchymal bodies were observed in 93% of all trichoepitheliomas, 7% of all keratotic BCC, and 0% of all routine BCC. Hair bulb formation was observed in 30% of trichoepitheliomas and in none of the BCC.

We conclude that papillary mesenchymal body formation is an easily recognizable histologic criterion that is more reliable in differentiating these two tumors than standard criteria, including epidermal connections, keratinization, calcification, foreign body reaction, fibrosis, stromal retraction, tumor mucin, ulceration, frondlike epithelial pattern, and the inflammatory response.

VARIANTS  
AMYLOID  

Secondary localized amyloidosis in trichoepithelioma. A light microscopic and ultrastructural study.

Lee YS, Fong PH. Department of Pathology and Medicine, National University of Singapore, Republic of Singapore.

Am J Dermatopathol 1990 Oct;12(5):469-78 Abstract quote

Two trichoepitheliomas with secondary localized amyloidosis were documented in a 74-year-old man. The ultrastructural findings support an origin of amyloid from tumor cells. It is suggested that the occurrence of amyloid is a reflection of the ability of tumor cells to produce an excessive number of tonofilaments from which amyloid is believed to be derived.

The intimate spatial association between amyloid and fibroblasts may suggest the existence of some yet undefined functional relationship.

BLUE NEVUS  

Blue naevus associated with trichoepithelioma: a report of two cases.

Newton JA, McGibbon DH.

Cutan Pathol 1984 Dec;11(6):549-52 Abstract quote

Naevocellular naevi may show considerable histological variation and have often been shown to contain other ectodermal elements, as well as cells of melanocytic origin. Blue naevi are also thought to be of melanocytic origin, and in this report we describe two blue naevi in which trichoepitheliomatous elements were seen.

The aetiological implications of this observation are discussed.

CYSTIC  

Cystic giant solitary trichoepithelioma.

Lorenzo MJ, Yebra-Pimentel MT, Peteiro C, Toribio J.

Department of Dermatology, General Hospital of Galicia, Faculty of Medicine, Santiago de Compostela, Spain.

Am J Dermatopathol 1992 Apr;14(2):155-60 Abstract quote

A case of a giant solitary trichoepithelioma is reported. The tumor was located on the thigh, extending from the deep dermis to the subcutaneous tissue with no epidermal contact, and showed a large central cystic cavity that measured 9 cm x 4 cm.

We review the cases published under this and other names.

DESMOPLASTIC  


Desmoplastic trichoepithelioma and intradermal nevus: a combined malformation.

Brownstein MH, Starink TM.

Laboratory of Dermatopathology, Port Washington, NY 11050.

J Am Acad Dermatol 1987 Sep;17(3):489-92 Abstract quote

We studied 13 desmoplastic trichoepitheliomas associated with intradermal nevi. Ten intradermal nevi were found among 76 new cases of desmoplastic trichoepithelioma (13%); three additional examples of the combined malformation were seen in consultation. Clinically, desmoplastic trichoepithelioma associated with an intradermal nevus was typically a small, firm or hard, sometimes annular, nodule on the face, particularly the cheek, of a relatively young woman.

Microscopically, the combined malformation contained narrow strands of basaloid cells and keratinous cysts in a desmoplastic stroma, intimately mixed with intradermal nests of nevocytes. Melanocytic nevi have been associated with epidermal hyperplasia resembling seborrheic keratoses, follicular cysts, trichostasis spinulosa, syringomas, basal cell carcinomas, and hair follicle formation on the soles.

The frequency of the occurrence of intradermal nevus with desmoplastic trichoepithelioma and the close anatomic association of the two elements may indicate that this combined malformation is another example of epithelial induction by melanocytic nevi.


Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study.

Hartschuh W, Schulz T.

Department of Dermatology, University of Heidelberg, Germany.

J Cutan Pathol 1995 Oct;22(5):413-21 Abstract quote

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n = 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n = 30).

Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered.

Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.


Desmoplastic trichoepithelioma of the upper lip. A case report with histochemical features and observations on its histogenesis.

Triantafyllou A, Scott J, Blacklock A.

Academic Unit of Oral Diseases, University of Liverpool School of Dentistry, UK.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995 Oct;80(4):445-50 Abstract quote

A case of desmoplastic trichoepithelioma of the upper lip investigated by histochemistry and immunocytochemistry is presented. There was histologic suggestion of cytoplasmic vacuolation that does not appear to have been previously described.

Histochemical examination indicated the presence of glycogen within tumor cells and a reparative-type stroma. Immunocytochemical examination revealed variable reactivity for high molecular weight cytokeratin and colonization by Langerhans' cells. The observations suggest a follicular and sudoriferous differentiation for desmoplastic trichoepithelioma and hence an origin from a pluripotential adnexal keratinocyte.

Desmoplastic trichoepithelioma.

Zuccati G, Massi D, Mastrolorenzo A, Urbano FG, Paoli S, Reali UM.

Istituto di Clinica Dermosifilopatica, Universita degli Studi di Firenze, Florence, Italy.

Australas J Dermatol 1998 Nov;39(4):273-4 Abstract quote

A 20-year-old male presented with a 4 year history of a solitary nodule, 8 mm in diameter on the left temple. It was covered by normal skin, with a central depression and elevated borders. Histopathology showed numerous horn cysts amidst nests and strands of basaloid cells surrounded by a dense fibrous stroma.

The clinical and histopathological features were characteristic of desmoplastic trichoepithelioma.

IMMATURE  

Immature trichoepithelioma: report of six cases.

Long SA, Hurt MA, Santa Cruz DJ.

Department of Pathology, St. John's Mercy Medical Center, St. Louis, Missouri

J Cutan Pathol 1988 Dec;15(6):353-8 Abstract quote

We report 6 cases of an immature variant of trichoepithelioma which histologically appears to show differentiation toward the primitive hair germ. The lesions presented in mature adults (mean age 44 years). Four occurred in men and 2 in women. Four lesions occurred on extremities, an unusual location for trichoepitheliomas. Histologically, the lesions were characterized by well-circumscribed, but unencapsulated, dermal collections of small tumor lobules composed of basaloid cells with invaginations resembling primitive dermal hair papillae. There was no adenoidal growth pattern or horn cyst formation. The separation of the immature lesions from those of classical trichoepithelioma and basal cell carcinoma can be made if multiple morphological features are considered; no one particular finding is diagnostic. The major differential features between the immature trichoepithelioma and basal cell carcinoma are circumscription, tumor lobule uniformity, occasional immature hair germs, and lack of retraction artifact of the tumor lobules from the stroma. The differential features between the immature and classical trichoepithelioma are less conspicuous.

The immature form typically exhibits no horn cysts, displays fewer primitive hair structures, and lacks the adenoidal growth patterns of the tumor lobules which are usually present in the classical trichoepitheliomas.

MELANOCYTIC NEVUS  

Desmoplastic trichoepithelioma and intradermal nevus: a combined malformation.

Brownstein MH, Starink TM.

Laboratory of Dermatopathology, Port Washington, NY

J Am Acad Dermatol 1987 Sep;17(3):489-92 Abstract quote

We studied 13 desmoplastic trichoepitheliomas associated with intradermal nevi.

Ten intradermal nevi were found among 76 new cases of desmoplastic trichoepithelioma (13%); three additional examples of the combined malformation were seen in consultation. Clinically, desmoplastic trichoepithelioma associated with an intradermal nevus was typically a small, firm or hard, sometimes annular, nodule on the face, particularly the cheek, of a relatively young woman.

Microscopically, the combined malformation contained narrow strands of basaloid cells and keratinous cysts in a desmoplastic stroma, intimately mixed with intradermal nests of nevocytes. Melanocytic nevi have been associated with epidermal hyperplasia resembling seborrheic keratoses, follicular cysts, trichostasis spinulosa, syringomas, basal cell carcinomas, and hair follicle formation on the soles.

The frequency of the occurrence of intradermal nevus with desmoplastic trichoepithelioma and the close anatomic association of the two elements may indicate that this combined malformation is another example of epithelial induction by melanocytic nevi.

MONSTER STROMAL CELLS  

Trichoepithelioma with "monster" stromal cells.

Rivet J, Rogez C, Wechsler J.

Department of Pathology, Hospital Saint Louis, Paris, France.

J Cutan Pathol 2001 Aug;28(7):379-82 Abstract quote

Trichoepithelioma is a benign tumor of trichogenic origin which appears predominantly in childhood or in young adults. Different forms have been described according to clinical and histological features.

The authors report a unique variant of trichoepithelioma arising on the limb of a 27-year-old man. The tumor was characterized by the mixture of an atypical fibroxanthomatous proliferation and basaloid epithelial strands of trichoepithelioma. Such histological features have not been previously reported.

It raises the question of an additional variant of hair follicle tumor with a mixed epithelial and mesenchymal proliferation.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
Special stains  
Immunoperoxidase  
DESMOPLASTIC  



Immunohistochemical and ultrastructural observations of desmoplastic trichoepithelioma with a special reference to a morphological comparison with normal apocrine acrosyringeum

Osamu Yamamoto
Tetsuo Hamada
Yoshiaki Doi
Yasuyuki Sasaguri
Hiroshi Hashimoto

J Cutan Pathol 2002;29:15 Abstract quote

Background: Desmoplastic trichoepithelioma is a benign neoplasm considered to have follicular differentiation. Its sweat gland- or sebaceous-lines of differentiation have been also reported. There have been, however, only a few reports regarding extensive immunohistochemical and ultrastructural investigations of this neoplasm.

Methods: Histopathological and immunohistochemical studies were performed on three cases of desmoplastic trichoepithelioma, comparing it with normal skin. One of these cases was ultrastructurally investigated.

Results: The cord-like basaloid nests were reacted with the anti-cytokeratin (CK)1/5/10/14, -CK5/8, -CK14 and -CK15 antibodies, but not with the anti-CK6 antibody. Similar findings were observed in the outer layers of the normal follicular outer root sheath. Basaloid cell nests in one case, which showed ductal structures in the nests, also expressed CK7, CK8/18 and CK19. These keratins were also detected in the normal sweat glands. In addition, CK8/18 and CK19 were expressed in the basal cells of the outer root sheath. Keratinous cysts had inner reactions with the anti-CK10/11 and -CK6 antibodies, and outer reactions with anti-CK5/8 and -CK14 antibodies. Ultrastructurally, the cells in the cord-like nests were basically immature and basaloid in appearance. A few cells contained Odland bodies, which were also observed in the normal apocrine acrosyringeum. The ductal structure was lined by the cells which bore numerous microvilli in the luminal surface.

Conclusion: The cells in desmoplastic trichoepithelioma are suggested to be in close association with the basal cells in the outer root sheath, which can differentiate into various parts of the folliculosebaceous apocrine unit.

GENERAL  
ANDROGEN RECEPTOR  
Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors.

Izikson L, Bhan A, Zembowicz A.

Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Am J Dermatopathol. 2005 Apr;27(2):91-5. Abstract quote  

Histologic differentiation between basal cell carcinoma and benign trichoblastic neoplasms such as trichoepithelioma and trichoblastoma can be difficult on small biopsies. Therefore, several attempts have been made to identify immunohistochemical differences between these entities. Recent studies have shown androgen receptor expression in a number of mature epithelial structures in the skin and in epithelial neoplasms including basal cell carcinoma. In contrast, androgen receptor expression was absent in mature hair follicles or the few trichogenic neoplasms studied to date. These findings suggested that androgen receptor expression might be a useful adjunct in the histologic differential diagnosis between basal cell carcinoma and benign trichoblastic neoplasms.

Therefore, we performed immunohistochemical analysis of androgen receptor expression in 32 basal cell carcinomas and 10 benign trichoblastic tumors (6 trichoepitheliomas and 4 trichoblastomas). In our study, at least focal expression of androgen receptor was detected in 78% of basal cell carcinomas. None of the trichoblastic tumors showed any androgen receptor immunoreactivity.

These results confirm the lack of expression of androgen receptor in benign trichoblastic neoplasms and indicate that androgen receptor expression by tumor cells points to basal cell carcinoma as the most likely diagnosis.
CD34  

CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma.

Kirchmann TT, Prieto VG, Smoller BR.

Department of Dermatology, Stanford University Medical Center, Calif.

Arch Dermatol 1994 May;130(5):589-92 Abstract quote

BACKGROUND AND DESIGN: Trichoepithelioma is a benign skin tumor with follicular differentiation, which sometimes is difficult to distinguish clinically and histologically from basal cell carcinoma. One of the most helpful differences is the histologic appearance of the stroma. CD34 is an antigen known to stain the spindle-shaped cells located around the middle portion of normal hair follicles. We have stained formalin-fixed, paraffin-embedded sections of 16 trichoepitheliomas and 19 basal cell carcinomas for CD34 (anti-HPCA-1, Becton Dickinson, San Jose, Calif) to detect differences in the staining pattern and to facilitate discrimination of these two types of tumors.

RESULTS: The spindle-shaped cells surrounding the islands of trichoepithelioma cells were focally strongly positive for CD34. In all basal cell carcinomas, the spindle-shaped cells surrounding the nests of tumor cells were negative; in these areas only the blood vessels were positive with this antibody.

CONCLUSIONS: CD34 staining pattern differentiates between trichoepithelioma and basal cell carcinoma. CD34 stain may be helpful in distinguishing between these two tumors on small punch biopsies or in difficult diagnostic cases.

Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens.

Swanson PE, Fitzpatrick MM, Ritter JH, Glusac EJ, Wick MR.

Division of Dermatopathology, Washington University School of Medicine, St. Louis, Missouri, USA.

J Cutan Pathol 1998 Mar;25(3):153-9 Abstract quote

The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that the expression of bcl-2 or CD34 antigen is able to distinguish BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number.

In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. 'Peripheral' bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas.

These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other than conventional microscopy that can be applied successfully to the latter problem.

An immunohistochemical study of basal cell carcinoma and trichoepithelioma.

Poniecka AW, Alexis JB. Arkadi M. Rywlin M.D.

Department of Pathology & Laboratory Medicine, Mount Sinai Medical Center, Miami, Florida, USA.

Am J Dermatopathol 1999 Aug;21(4):332-6 Abstract quote

The histologic distinction between tricheopithelioma and basal cell carcinoma may be difficult in small biopsies. Immunohistochemical stains have been used to help make this distinction; however, published studies have generally been limited to a few antibodies.

To this end we performed a comprehensive immunohistochemical analysis of 20 basal cell carcinomas and 10 tricheopitheliomas from our files, in search of a consistent pattern of reactivity to distinguish the neoplasms in biopsies. The antibodies used were: low molecular weight keratin (Cam 5.2), Cytokeratin 7, (CK7), Cytokeratin 20, (CK20), Carcino-embryonic antigen (CEA), CD30 (Ki-1), bcl-2, Ham 56, HPCA-I (CD34), and Ulex Europaeus type I.

In our study, bcl-2 stained all but one basal cell carcinoma in a diffuse pattern, whereas all tricheopitheliomas showed staining of the outermost epithelial layer. No other stain proved to be an independent marker for either neoplasm and no consistent immunohistochemical profile for either neoplasm emerged.

Thus, we conclude that bcl-2 may be of some value in distinguishing basal cell carcinoma from tricheopithelioma, limited by the quantitative nature of the difference in staining. Histologic criteria applied to H&E-stained sections remain the cornerstone of histologic diagnosis.

p16  
p16 expression in conventional and desmoplastic trichilemmomas.

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0009, USA.

 

Am J Dermatopathol. 2009 Jun;31(4):342-9. Abstract quote

The expression of p16 in cutaneous neoplasms is upregulated in melanocytic neoplasms, ultraviolet radiation-induced neoplasms, such as actinic keratoses and squamous cell carcinomas, and in lesions related to human papillomavirus, such as Bowen's disease and bowenoid papulosis. In cervical dysplasia and tonsillar carcinoma, there is such a close relationship between p16 and human papillomavirus (HPV) to the extent that p16 immunostaining is used as a surrogate marker for the presence of HPV proteins.
 
In this study we were interested in the expression pattern of p16 in trichilemmomas. Twenty-six conventional and 19 desmoplastic trichilemmomas were immunohistochemically stained for p16. p16 immunostaining was noted in the majority of conventional (80.8%) and desmoplastic trichilemmomas (73.7%). The staining pattern was both nuclear and cytoplasmic. The staining intensity was more pronounced in the desmoplastic variant.
 
We describe for the first time p16 expression in trichilemmomas and discuss our findings in conjunction with p16 expression found in other cutaneous neoplasms. Additionally, the relationship of p16 to HPV infection is critically evaluated.
p27  


Expression of p27kip1 in Basal Cell Carcinomas and Trichoepitheliomas.

Cesinaro AM, Migaldi M, Corrado S, Maiorana A.

Section of Pathological Anatomy, Department of Morphologic and Forensic Sciences, University of Modena and Reggio-Emilia, Modena, Italy.

Am J Dermatopathol 2002 Aug;24(4):313-8 Abstract quote

Immunohistochemical analysis was used to evaluate p27kip1 expression in normal hair follicles and in a series of 39 basal cell carcinomas (BCC) (13 of superficial type, 7 infiltrating, 7 morphea-like, 12 nodular) and 20 trichoepitheliomas (TE) (9 of classic type, 9 immature, 2 desmoplastic).

The labeling index (LI) was derived semiautomatically by means of a computer-assisted cellular image analyzer, and statistical analysis was carried out using the Student t test. A positive reaction for p27kip1 was detected in the hair germ papillae, in supramatrical cells, and in the inner pilar sheath, whereas matrical cells and the outer pilar sheath were negative. All BCC and TE cases showed a positive immunoreaction for p27kip1, but the staining pattern was different in the two groups of lesions, being patchy with focal peripheral accentuation in TE and more diffusely dispersed in BCC. The quantitative study showed lower p27kip1 expression in BCC (LI = 27.51 +/- 12.55) than in TE (LI = 45.27 +/- 20.27) (P < 0.0001). Statistically significant differences were also observed between TE subgroups and nodular or infiltrating BCC subtypes.

The occurrence of a wide overlap of LI values hampers the practical application of a p27kip1 LI in the differential diagnosis between BCC and TE in difficult cases, however.

Electron microscopy (EM)  

Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study.

Hartschuh W, Schulz T. Department of Dermatology, University of Heidelberg, Germany.

J Cutan Pathol 1995 Oct;22(5):413-21 Abstract quote

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation.

In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n = 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n = 30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered.

Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
BASAL CELL CARCINOMA  

Does the panel of cytokeratin 20 and androgen receptor antibodies differentiate desmoplastic trichoepithelioma from morpheaform/
infiltrative basal cell carcinoma?

  • 1Department of Pathology, 2Division of Biostatistics, Department of Medicine and 3Department of Pathology and Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA
Katona TM, Perkins SM, Billings SD.

J Cutan Pathol 2008;35:174-179 Abstract quote

Background: Evaluation of androgen receptor (AR) and cytokeratin 20 (CK20) expression can aid in distinguishing between conventional basal cell carcinoma (characteristically AR+, CK20−) and trichoepithelioma (frequently AR−, CK20+). Within these two groups of tumors, morpheaform/infiltrative basal cell carcinoma (mBCC) and desmoplastic trichoepithelioma (DTE) are particularly challenging to differentiate both clinically and histologically. We investigated whether AR and CK20 immunostains may distinguish between mBCC and DTE.

Methods: Immunohistochemistry for AR and CK20 was performed on 15 DTEs and 31 mBCCs. Any immunoreactivity within the tumor for AR or CK20 was considered positive.

Results: AR expression was seen in 13% (2/15) of DTE and 65% (20/31) of mBCC cases (chi-square p = 0.0011). CK20-positive Mërkel cells were identified in 100% (15/15) of DTE and 3% (1/31) of mBCC (chi-square p < 0.0001). The expected pattern of AR−, CK20+ immunophenotype was present in 87% (13/15) of DTE cases. In mBCC, 61% (19/31) was AR+, CK20−. No DTE was AR+, CK20− and no mBCC was AR−, CK20+.

Conclusions: Immunohistochemical stains for AR and CK20 are useful to differentiate DTE from mBCC. The AR−, CK20+ immunophenotype is sensitive (87%) and specific for DTE (100%). The AR+, CK20− immunophenotype is specific (100%) and moderately sensitive (61%) for mBCC.


Proliferative characterization of basal-cell carcinoma and trichoepithelioma in small biopsy specimens.

Lum CA, Binder SW.

Division of Surgical Pathology, LAC-USC Medical Center, USC-Keck School of Medicine, Los Angeles, CA, USA.

J Cutan Pathol. 2004 Sep;31(8):550-4. Abstract quote  

We examined the proliferative characteristics of 20 basal-cell carcinomas (BCCs) and 16 trichoepitheliomas (TEps) in an effort to understand and explore possible differences in their tumorigenic cell-cycle properties. These tumors were first compared for their expression of the nuclear proliferative protein Ki-67 and the tumor suppressor protein p53. We also compared the p53 downstream effector, p21(waf-1/cip-1), an inhibitor of cyclin-dependent kinases. The other p53-dependent, cyclin-dependent kinase inhibitor, p27(kip-1), has shown to be increased in TEps, which is consistent with this benign neoplasm's better-differentiated state.

In our findings, we confirmed through immunohistochemical staining for Ki-67 that BCCs qualitatively showed a greater proliferative fraction compared to TEps (50.0 vs. 13.0%, p < 0.00001) as well as over-expression of p53 (2+ vs. 1+, p < 0.0008). BCCs marked by p21 demonstrated scattered nuclear positivity compared to the virtual absence of staining in the TEps (p < 0.019). In studying their cell-cycle properties, our findings suggest that abnormalities in the p53 pathway allow BCCs to obtain a growth advantage.

We show that Ki-67 and p53 staining both appear useful in resolving challenging differential diagnoses and thereby help in directing appropriate treatment strategies.

Criteria for histologic differentiation of desmoplastic trichoepithelioma (sclerosing epithelial hamartoma) from morphea-like basal-cell carcinoma.

Takei Y, Fukushiro S, Ackerman AB.

 

Am J Dermatopathol 1985 Jun;7(3):207-21 Abstract quote

Histological differentiation between desmoplastic trichoepithelioma and morphea-like basal-cell carcinoma may be exceedingly difficult. Because the criteria for this differentiation published to date have not proved satisfactory to us, we undertook a study with the aim of formulating repeatable and reliable criteria for distinguishing between these two conditions of wholly different biological potential.

We believe that the 26 sets of criteria listed here will permit reliable differentiation of desmoplastic trichoepitheliomas from morphea-like basal-cell carcinomas, even in biopsy specimens taken by shave and punch techniques.

Trichoepithelioma: a 19-year clinicopathologic re-evaluation.

Bettencourt MS, Prieto VG, Shea CR.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

J Cutan Pathol 1999 Sep;26(8):398-404 Abstract quote

Accurate histopathologic distinction between trichoepithelioma (TE) and basal cell carcinoma (BCC) may be challenging.

From 97 cases diagnosed as TE during the period 1979-1997, 73 available cases were studied with regard to: 1) stroma; 2) retraction effect; 3) papillary-mesenchymal bodies (PMB); 4) amyloid; 5) mitotic figures; 6) apoptotic cells; 7) inflammation; 8) granuloma; and 9) calcification.

A judgment was made regarding diagnosis. The patients' medical records were subsequently reviewed for clinical features and possible recurrence. The diagnosis of TE was confirmed histologically in 48 (65%) of 73 cases. Fifteen cases (21%) were reclassified as BCC (RC-BCC), eight other cases (11%) were reclassified as other lesions, and two additional cases (3%) could not be confidently classified as either TE or BCC.

The most helpful differentiating features were the presence of retraction effect (in 100% of RC-BCC vs. 37% of TE), myxoid stroma (in 80% of RC-BCC vs. 12% of TE) and PMB (in 20% of RC-BCC vs. 81% of TE). Unexpected findings in TE were detection of amyloid in 33%, apoptotic cells in 100%, and mitotic figures in 46%.

Five of the 15 RC-BCC have recurred (33%), whereas there have been no recurrences in the confirmed TE group.

A constellation of histopathologic criteria may help to discriminate problematic examples of trichoepithelioma from basal cell carcinoma.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
Prognostic Factors  
Recurrence None to rare

Recurrent solitary giant trichoepithelioma located in the perianal area; a case report.

Beck S, Cotton DW.

Department of Pathology, General Hospital, Rotherham, U.K.

Br J Dermatol 1988 Apr;118(4):563-6 Abstract quote

A case of giant solitary trichoepithelioma of the perianal region is described. Following excision the lesion recurred with a similar histological appearance.

This is the first report, to our knowledge, of recurrence of such a lesion.

Metastasis None
Treatment Simple excision

Cryotherapy for multiple trichoepithelioma.

Duhra P, Paul JC.

Skin Hospital, Edgbaston, Birmingham, U.K.

J Dermatol Surg Oncol 1988 Dec;14(12):1413-5 Abstract quote

Multiple trichoepithelioma is an uncommon disorder for which treatment is usually bedeviled by the recurrence of tumors. A case of multiple trichoepithelioma is described occurring in the retroauricular area; the condition cleared completely and without relapse following cryotherapy.

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DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
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