Malignant transformation of multiple adnexal tumors in a Filipino-American patient with Brooke-Spiegler Syndrome: A case report

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> Trichoepithelioma is a benign hamartoma which may exhibit similar clinical and histopathological features with basal cell carcinoma. Since prognosis is dissimilar, differentiating between them is important. Literature reveals fifteen reports of malignant transformation of multiple trichoepitheliomas into basal cell carcinoma, with none in the local setting. In Brooke-Spiegler syndrome, the incidence rate of malignant transformation of benign neoplasms has been reported in 5-10 % of patients.</p><p style="text-align: justify;"><strong>CASE REPORT:</strong> A 53-year-old Filipino-American female presented with multiple discrete to coalesced, well-defined, skin-colored to hyperpigmented, smooth, dome-shaped, rubbery papules and nodules on the face since childhood. Throughout the years, lesions increased in number and size and spread to the scalp, chest, abdomen, back, upper and posterior right thigh. Some developed ulceration, telangiectasia and pigmentation.</p><p style="text-align: justify;">Chest radiography, radiographs of the jaw, whole abdominal ultrasound, cranial CT scan, ophthalmology and otorhinolaryngology assessments were normal. Based on clinical and histopathologic findings, the final diagnosis was Brooke-Spiegler syndrome with transformation into basal cell carcinoma. Carbon dioxide (CO2) laser was used to excise large and ulcerated lesions with good cosmetic results.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> A case of a Filipino-American adult female diagnosed clinically and histologically with Brooke-Spiegler syndrome with transformation into basal cell carcinoma was presented. Given the similarities in clinical and histopathologic features of trichoepithelioma and basal cell carcinoma, accurate diagnosis should be made because of their difference in prognosis. The use of an acceptable treatment modality such as carbon dioxide (CO2) laser in this case is an important emerging fi eld of study.</p><p style="text-align: justify;"><strong>KEYWORDS:</strong> trichoepithelioma, basal cell carcinoma, Brooke-Spiegler syndrome, malignant transformation, carbon dioxide laser</p>

Síndrome de Brooke-Spiegler asociado a carcinoma basocelular: reporte de caso / Brooke-Spiegler syndrome associated with basal cell carcinoma: case report

El síndrome de Brooke-Spiegler (SBS) es una entidad rara, autosómica dominante, que ocurre por mutaciones del gen CYLD, el cual funciona como supresor de tumores. Se presenta el caso de una mujer de 50 años de edad, con historia de aparición de lesiones características de tricoepiteliomas que predominaban en nariz, región interciliar y mentón, que iniciaron desde los 14 años de edad. Desde hace 5 años refiere aumento del tamaño de lesiones en alas nasales, y una lesión en punta nasal de 2 años de evolución. Al realizarse una correlación clínica e histológica, asociada a los antecedentes familiares de la madre y hermano de la paciente, se concluyó que el cuadro clínico era compatible con tricoepitelioma múltiple familiar, una variante especial del SBS, en este caso asociado a carcinoma basocelular, que aunque no es un hallazgo común, se ha visto que se puede presentar en esta enfermedad. El diagnóstico preciso de SBS requiere de una correlación clínico-histológica, y se debe hacer un seguimiento clínico cercano para detectar cambios en las lesiones en piel, que puedan indicar una transformación maligna

Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant condition that occurs due to mutations in the CYLD gene, which functions as a tumor suppressor gene. The case of a 50-year-old woman with a history of characteristic trichoepitheliomas predominantly in the nose, glabella and chin that began at 14 years of age is presented. She reports an increase in the size of the nasal ala lesions for the past 5 years, and the appearance of a new lesion in the nasal tip 2 years ago. When performing a clinical and histological correlation, associated with family history in both the mother and brother, it was concluded that the diagnosis was compatible with multiple familial trichoepithelioma, a special variant of BSS, associated in this case with basal cell carcinoma, that although not a common finding, has been seen to coexist in this disease. The diagnosis of BSS requires a clinical and histological correlation, and a close clinical follow-up must be performed to detect changes in the skin lesions that may indicate malignant transformation

Immunohistochemical expression of CK19, AR, PHLDA1, CD10 and Ki67 in the differentiation between Trichoepithelioma and Basal Cell Carcinoma: A systematic review

Background@#Basal cell carcinoma (BCC) and trichoepithelioma (TE) are follicular adnexal neoplasms that arise from the follicular germ but with divergent biological behavior. The gold standard in the differentiation is through histopathological examination using hematoxylin and eosin (H and E) stain. There are cases, however, when the distinction is not straightforward. @*Objective@#To assess the association and diagnostic accuracy of the immunohistochemical (IHC) expressions of CD10, Ki67, CK19, androgen receptor (AR), and PHLDA1 in distinguishing between basal cell carcinoma and trichoepithelioma. @*Methods@#We conducted a comprehensive search on cross-sectional studies on human tissue from 2000 to 2020 in MEDLINE (PubMed), CENTRAL and EMBASE for comparative studies and reference lists. The data were summarized and analyzed using Microsoft Excel and RevMan. We used Chi-square test for independence, summary receiver operator curves (sROC), and diagnostic odds ratio (OR). @*Results@#We included 15 articles containing 686 BCC and 367 TE in the systematic review. The pooled staining of biomarkers showed a significant difference in the staining of CK19 (p<0.05) and AR (p<0.0001), and PHLDA1 (p<0.0001). Diagnostic odds ratio was used to confirm these associations. AR was found to have the highest odds in the diagnosis of BCC (OR 27.92, 95% CI 10.69, 72.86). The pattern of staining of CD10 is significant (p<0.001) with staining of both tumor and stroma (OR 8.09, 95% CI 4.57, 13.53) and staining of tumor alone (OR 8.15, 95% CI 4.56, 14.35) (p<0.001) in the diagnosis of BCC. CD10 stromal staining, on the other hand, is significantly associated with the diagnosis of TE (OR 7.26, 95% CI 5.06, 10.44) (p<0.0001). There is no significant association between Ki67 staining (OR 1.22, 95% CI 0.48, 3.09) (p=0.67) and the diagnosis of BCC. The forest plot and sROC showed that AR had high specificity across all included studies in the diagnosis of basal cell carcinoma, while PHLDA1 demonstrated high specificity and high sensitivity in diagnosing trichoepithelioma. @*Conclusion@#The biomarkers AR and PHLDA1 are useful as an initial panel to distinguish between BCC and TE, given that both showed high sensitivity as well as significant association with BCC and TE respectively. CD10 and CK19 may also be used with AR and PHLDA1 for further confirmation.

Analysis of imaging characteristics of trichoepithelioma / 中华皮肤科杂志

Objective To investigate dermoscopic,reflectance confocal microscopic (RCM) and histopathological features of trichoepithelioma.Methods A total of 23 outpatients with histopathologically confirmed trichoepithelioma were enrolled from Department of Dermatology,Wuhan No.1 Hospital between January 2017 and December 2018.Dermoscopic and RCM images were collected,and the consistency was analyzed between dermoscopic or RCM features and histopathological features.Results Among the 23 patients,5 were male,and 18 were female.Their age was 39.5 ± 22.1 years.Histopathological examination showed that the tumor was well-circumscribed and surrounded by abundant fiber matrices,consisted of many basaloid cells forming clusters or interlacing cords with surrounding cells arranged in a fence-like pattern.Tumor cells differentiated into dermal papilla cells to different extents,and varying amounts of keratinous cysts were observed.RCM showed bud-like downward extension of cord-like cells at the dermoepidermal junction in 8 patients,which tended to be arranged in a fence-like pattern;seemingly lobulating nodular tumor masses were scattered in the dermis in 18 patients,which appeared as extended hypoechoic structures,with no constriction gap between tumor masses and surrounding tissues;tumor masses were surrounded by moderately to highly refractive amorphous substance in 16 patients;characteristic hair papilla structures suspected to be derived from primary differentiation were observed in 16 patients;keratinous cysts were clearly observed in 20 patients.Dermoscopy clearly showed that homogeneous pearlwhite structures in 20 patients,and linear telangiectasia in 10 patients.Conclusion RCM features of trichoepithelioma are highly consistent with its histopathological features,so reflectance confocal microscopy can serve as an efficient method for auxiliary and differential diagnosis.

Trichoblastic carcinoma arising in trichoepithelioma in Brooke–Spiegler syndrome

Brooke–Spiegler syndrome (BSS) is a rare autosomal dominant disease characterized by the development of multiple cutaneous adnexal neoplasms namely cylindroma, trichoepithelioma and spiradenoma. The neoplasms associated with this syndrome are generally benign, but rarely they may undergo malignant transformation. A 63-year-old male presented with an ulcerated nodular lesion over glabella and multiple asymptomatic nodular lesions over face, scalp, chest and limbs. His father, grandfather and paternal cousins had history of similar lesions. Histopathological examination revealed trichoblastic carcinoma arising from trichoepithelioma over glabella and cylindroma on the chest. With these findings we arrived at a diagnosis of BSS with malignant transformation of trichoepithelioma. Trichoblastic carcinoma arising in trichoepithelioma in a patient with BSS is extremely rare with only a single case reported in literature.

A Spectrum Of Skin Adnexal Tumors

Background: Troublesome tumors (Skin adnexal tumors (SAT)) pose a major diagnostic difficulties because of their wide spectrum and variants, their rarity, differentiation along two or more adnexal lines and their complicated nomenclature to both the surgeon and the pathologist. Histopathology is the gold standard of diagnosis with immunohistochemistry playing a limited role.Materials and methods: A Prospective study of skin adnexal tumors (n =25) diagnosed on histopathological examination over a period of 2 years (June 2015 to May 2017). All slides were stained with H & E.Results: Majority of the patients are in the third and fourth decade. Females outnumbered the males.Twenty-two tumors are benign and 3 are malignant. Most common skin adnexal tumors are Hair follicle origin tumors comprising of 15cases (60%). In that most common benign tumor is Trichoepithelioma. Head and neck region is the commonest site involved.Conclusion: Skin adnexal tumors are relatively rare. Benign adnexal tumors are more common than the malignant lesions. Histopathology is essential to confirm the diagnosis.

Tricoepitelioma múltiple familiar: a propósito de un caso / Familial multiple trichoepithelioma: a case report

El Tricoepitelioma Múltiple Familiar (TMF) constituye una rara enfermedad autosómica dominante, se caracteriza por la aparición de múltiples pápulas color piel, monomorfas, simétricas, ubicadas en la región central de la cara. El diagnóstico es histopatológico, donde se encuentran tricoepiteliomas, los cuales son neoplasias anexiales benignas que se originan en los folículos pilosos. La condición es de comportamiento indolente, pero con una importante repercusión estética y de difícil manejo. Al ser esta una entidad poco frecuente, el objetivo de este artículo es actualizar los aspectos más relevantes de esta enfermedad. Se presenta el caso de una paciente de 23 años con lesiones faciales típicas en quien se confirmó el diagnostico de TMF

Familial Multiple Trichoepithelioma (FMT) is a rare autosomal dominant disease, characte-rized by the appearance of multiple papules of skin color, monomorphic, symmetrical and located in the central region of the face. The diagnosis is based on histopathological features of trichoepitheliomas, which are benign adnexal neoplasms that originate in the hair follicles. The condition has an indolent behavior but it has an important aesthetic repercussion and it's difficult to treat. As this is a rare entity, the objective of this article is to update the most relevant aspects of this disease. We present the case of a 23 year old patient with typical facial lesions in whom the diagnosis of FMT was confirmed.

Masquerades less known: Case report of benign hair follicle tumors

Benign eyelid tumors derived from hair follicles are rare and frequently misdiagnosed as basal-cell carcinoma when evaluation is based on clinical evidence alone. The discrepancy between the clinical aspect and the histological diagnosis can be as high as 30–40%, even for experienced clinicians. Unfortunately, this masquerade is not only clinical but also histological. Patients may be subjected to unnecessarily extensive surgery. We present a case report of three patients clinically diagnosed as malignancy but histopathologically proven as benign hair follicle tumors.

Desmoplastic trichoepithelioma complicated by sebaceous hyperplasia: a case report / 中华皮肤科杂志

A 67-year-old male patient presented with a plaque on the top of the head for more than 1 year.Physical examination showed an annular pale red plaque sized about 1.5 cm × 1 cm on the top of the head.It had a depressed center and papule-like elevated faint yellow boundaries,and there was no hair on the surface of the lesion.Histopathologic examination revealed milder epidermal hyperplasia,a small area of epidermal depression,confluence and hyperplasia of multiple sebaceous glands in the dermis,many keratinous cysts and funicular basophilic epithelial cells surrounded by hyperplastic collagen fibers in the superficial dermis.Immunohistochemical study showed positive staining for CD34 (hair mesenchymal cells),epithelial membrane antigen (EMA),cytokeratin 20 (CK20),but negative staining for bcl-2,P53,CD56 and collagen Ⅳ,with the proliferation index Ki-67 of 2％-5％.Based on the pathological results,the patient was diagnosed with desmoplastic trichoepithelioma complicated by sebaceous hyperplasia.

Histopathological Study of Skin Adnexal Tumors – A Ten Years Study

Background: Adnexal tumors of skin are uncommon in routine practice and may cause diagnostic problems clinically. Presence of Multiple tumors can be considered as marker for visceral malignancy e.g. multiple trichilemmoma-breast malignancy. Adenexal tumors of the skin are classified into four groups. Aim: To correlate skin adenexal tumors with age, sex and location and incidence in the Department of Pathology, Gandhi Hospital, Hyderabad. Materials and methods: Total number of cases was 136, during study period from April 2007 to March 2017 (ten years) in present study. All slides stained with routine Hematoxylin and Eosin and special stains accordingly. Results: Total number of Adenexal tumors were 136; benign tumors were 134 (98.4%), malignant tumors were 02 (1.6%), Largest group was sweat gland tumors (42.1%) e.g. chondroid syringoma, eccrine poroma, syringo cystadenoma papilleferum, hair follicle tumors (35.4%) e.g. trichoepithelioma, pilomatricoma and sebaceous adenoma and sebaceous carcinoma. Undifferentiated and others (21%) e.g. benign trichogenic tumors were also noted. Conclusion: The incidence of benign skin adenexal tumors was more as compared with the malignant tumors. Malignant tumors were seen predominantly in elderly

Solitary Trichoepithelioma Occurred on Unusual Site of Leg / 대한피부과학회지

No abstract available.

A Case of Solitary Trichoepithelioma on the Toe / 대한피부과학회지

Trichoepithelioma (TE) is a benign lesion that arises from hair follicles. Solitary TE occurs mainly on the face in young adults. Various previous reports have described the localization of this disorder, but there have been no reported cases with presentation on the toe. Histopathologically, TE shares characteristic features with basal cell carcinoma (BCC), so immunohistochemical stains are required for the differential diagnosis. Therefore, we report the first case of TE occurring on the toe, confirmed with immunohistochemial differentiation.

Microcystic Adnexal Carcinoma Misdiagnosed as Desmoplastic Trichoepithelioma on Preoperative Biopsy

Microcystic adnexal carcinoma is a rare type of tumor, with about 300 cases reported globally. Due to its similar histology with other tumors, it is occasionally misdiagnosed as desmoplastic trichoepithelioma, basal cell carcinoma, syringoma, and so on. We present a patient with a mass on the perioral area who was preoperatively diagnosed with trichoepithelioma. Microcystic adnexal carcinoma was diagnosed after excisional biopsy and a wide excision. Defects were reconstructed with a mucosal advancement flap. There was no recurrence and there were no significant complications during the 18-month follow-up period. Because superficial punch biopsy has limitations in width and depth, surgeons should always consider the possibility of malignancy of a mass even if a biopsy shows a benign result.

Trichoepithelioma Multiplex: A Study of the Relationship between the Anatomical Location and the Histopathological Features.

Trichoepithelioma multiplex is a rare, benign cutaneous genodermatosis of disputed histogenesis, consisting of tumors of trichogenic origin. Aim: To explore the relationship between the anatomical location and the histopathological features of the trichoepitheliomas in a patient cohort with Trichoepitheliomamultiplex. Methods: The study was conducted over the period 1995-2008 at the tertiary Dermatology and Anatomical Pathology referral centers of the University of Pretoria. The clinical and pathological features of confirmed cases were assessed. Sixty four H&E stained sections from skin lesions distributed over different body areas were examined with regard to 16 histopathological parameters for the evidence of follicular differentiation and features useful in distinguishing trichoepithelioma from basal cell carcinoma. Special stains were employed for the demonstration of mucin (PAS, Alcian blue) amyloid (Congo red) calcium (Von Kossa) and epithelial structures (AE1/AE3-CK antibodies). Results:Trichoepithelioma multiplex was an uncommon diagnosis (20 patients). African patients were preponderant (16 vs.4 Caucasians) with slight male predominance (11 vs. 9 females). Sporadic cases prevailed (15 vs. 5 familial cases).A wide variation in the severity of the clinical presentation was observed, young black males and familial cases being more severely affected. The face was involved in all cases (30 biopsies), followed by the scalp and back (13 biopsies each) and the neck (8 biopsies). There were variations in histopathological patterns with considerable overlap between them. Special stains differentiated between the tumours from different body areas with the exception of AE1/AE3-CK antibodies. Foreign body reactions were common in lesions showing many keratinous cysts and follicular damage. Trichoepithelioma was seen in relation to a benign pigmented intradermal nevus in one biopsy and adjacent to a basal cell carcinoma in two cases Conclusion: A positive correlation could be established between the histopathological pattern of trichoepitheliomas and the body area from which the lesions were removed.

Occurrence of trichoepithelioma in a cat：Histopathologic and immunohistochemical study

Trichoepitheliomas are benign follicular appendage tumors with differentiation to all three segments of the hair follicle. A 2 years old female domestic short hair cat presented with a mass on the tail. The mass was surgically excised and for histopathologic and immunohistochemical studies, was sent to Department of Pathology. Histologically, the tumor was encapsulated and consisted of many islands of follicular epithelium and also cysts structures which varied in size and shape. The cells of epithelium islands were round to oval and had variable amounts of slightly, eosinophilic cytoplasm and euchromatic nuclei. The cystic structures were lined by a complex layer of squamous epithelium. Often, cells under went an abrupt transition between basal layers and keratinization without the development of a granular cell layer. No tendency of malignancy was seen in this case. According to mentioned characteristics, trichoepithelioma was diagnosed. By immunohistochemical study it was confirmed that this tumor had epithelial origin because squamous tumor cells reacted with the pan-cytokeratin antibody. The expression of β-catenin was predominately cytoplasmic and also together with numerous positive nuclei but membranous expression was inconsistenet. Distribution of neoplastic cells with β-catenin expression was more than 75% and labeling intensity was strong in both cytoplasm and nuclei. According to author’s knowledge, this is the first report of trichoepithelioma in cat in Iran and also investigation of β-catenin expression in feline trichoepithelioma in veterinary literature.

Multiple Trichoepithelioma Improved by Intralesional Bleomycin Injection / 대한피부과학회지

Multiple trichoepithelioma is a benign adnexal neoplasm characterized by the presence of many small papules that appear predominantly on the face. Clinical improvement have been demonstrated after several treatments such as carbon dioxide laser, cryotherapy, dermabrasion, and argon laser. However, these destructive methods have various disadvantages. We report a case of multiple trichoepithelioma treated with an intralesional bleomycin injection. Fewer lesions without scars and cosmetic improvements were observed. Bleomycin is a cytotoxic antitumor antibiotic that can be injected intralesionally by transcutaneous administration and displays excellent results for treating malignancies including skin tumors. We believe that intralesional bleomycin injection is an effective treatment option for this condition, and an easy method to conduct at the outpatient clinic.

Imiquimod as an Adjuvant Treatment Measure for Desmoplastic Trichoepithelioma

Desmoplastic trichoepithelioma is a rare benign adnexal tumor. Although it is a benign lesion, patients often want to treat it due to cosmetic concerns when it occurs in an easily visible site. For our two cases, topical 5% imiquimod was an attractive treatment option as it is applied by the patients themselves and it has minimal side effects, including leaving no scar. However, the lesions recurred after clinical remission. To the best of our knowledge, this is the only report on utilizing imiquimod to treat a benign adnexal tumor, and especially desmoplastic trichoepithelioma.

A Case of Desmoplastic Trichoepithelioma / 대한피부과학회지

Desmoplastic trichoepithelioma is a rare, benign, adnexal tumor of hair follicle origin and is most commonly found on the face of young females. Clinically it presents as a solitary, asymptomatic, firm and annular plaque with a raised border. The histopathological findings show narrow strands of basaloid tumor cells with variable nests in a trabecular pattern and horn cysts in the desmoplastic stroma. This closely resembles morphea type basal cell carcinoma and microcystic adnexal carcinoma. We herein report a case of desmoplastic trichoepithelioma on the cheek of a 22-year-old man, with discussion of the significance of the immunohistochemical stains in the differential diagnosis of similar skin tumors, using antibodies for CD10, CD34, CEA, CK14, CK7 and Bcl-2.

A Case of Desmoplastic Trichoepithelioma, Showing Similar Histological Features to Microcystic Adnexal Carcinoma / 대한피부과학회지

Desmoplastic trichoepithelioma is a rare benign tumor which is most commonly found on the face of young females. The tumor has a raised, annular border and a depressed center. The histologic features are often confused with other skin diseases, especially with microcystic adnexal carcinoma. We report, herein, a case of desmoplastic trichoepithelioma in a 26-year-old man, confirmed by re-biopsy and CEA immunohistochemical study.

A Case of Multiple Trichoepithelioma with Turner's Syndrome / 대한피부과학회지

Trichoepithelioma is a benign epidermal appendage tumor with follicular differentiation. It occurs as a solitary non-familial and a multiple familial type. The multiple familial trichoepithelioma is a relatively common genetic dermatosis characterized by the presence of many small tumors predominantly on the face, which is inherited in an autosomal dominant pattern. The patient was a 18-year-old girl and presented multiple skin colored, pin head sized papules on the face. Skin biopsy revealed tumor islands composed of basophilic cells, showing peripheral palisading and multiple horn cysts. Also, the karyotype of 45, XO with typical clinical symptoms of Turner's syndrome was detected in this patient.