Current Diagnosis and Treatment Options for Cutaneous Adnexal Neoplasms with Apocrine and Eccrine Differentiation.

Adnexal tumors of the skin are a rare group of benign and malignant neoplasms that exhibit morphological differentiation toward one or more of the adnexal epithelium types present in normal skin. Tumors deriving from apocrine or eccrine glands are highly heterogeneous and represent various histological entities. Macroscopic and dermatoscopic features of these tumors are unspecific; therefore, a specialized pathological examination is required to correctly diagnose patients. Limited treatment guidelines of adnexal tumor cases are available; thus, therapy is still challenging. Patients should be referred to high-volume skin cancer centers to receive an appropriate multidisciplinary treatment, affecting their outcome. The purpose of this review is to summarize currently available data on pathogenesis, diagnosis, and treatment approach for apocrine and eccrine tumors.

Management of multiple trichoepithelioma: A review of pharmacological therapies.

Trichoepithelioma is a rare benign adnexal neoplasm that can occur in various forms including solitary, multiple, familial or nonfamilial. Multiple facial trichoepithelioma can be associated with significant psychosocial burden. Conventional treatment modalities such as surgical excision and ablative laser have variable results and can be associated with unacceptable complications and tumour regrowth. Pharmacological interventions such as topical and systemic agents are potentially effective but clinical data are limited and treatments are poorly standardised. We review the available evidence to determine the role of pharmacological therapies in the management of multiple trichoepithelioma. Demographic and clinical data were retrospectively collected from the available English literature. Majority of cases treated with pharmacological therapies (93.75%) had a positive treatment outcome, achieving partial lesion response. Adverse effects associated with pharmacological therapies were generally well tolerated and did not interrupt treatment. There are limitations as to how our results can be interpreted owing to the paucity of good quality evidence, spectrum of disease severity, and diversity of study designs utilised in the included articles. Nonetheless, the results of our study indicate that while most pharmacological interventions for multiple trichoepithelioma produce a partial response, they can be employed as effective suppressive therapies, either alone or in conjunction with conventional treatments. The current evidence for pharmacological therapies remains largely anecdotal justifying the need for further clinical studies in this area.

Periocular skin cancer: Diagnosis and management.

The periocular region sees high rates of cancer compared to the rest of the body and can be affected by several unique tumors. Treatment typically involves surgical excision, although adjunctive therapies and prognosis vary depending on the diagnosis. Basal cell carcinoma (BCC) is the most common malignancy affecting this region and should be excised promptly. This is followed by squamous cell carcinoma, which is often mistaken for BCC but is treated similarly. Melanoma is less common but more deadly, with relatively high rates of metastasis and death. Rare tumors that may be found in this region include sebaceous carcinoma, Merkel cell carcinoma, and microcystic adnexal carcinoma. While uncommon, these tumors are associated with poor outcomes and frequent recurrence. Recognition of periocular skin cancer is an important skill for primary care physicians, as prompt diagnosis and treatment can be sight or life-saving.

Behavior of Cutaneous Adnexal Malignancies: a Single Institution Experience.

Cutaneous adnexal malignancies are biologically and pathologically diverse, and associated with a range of clinical outcomes. Given their rarity, the prognosis and optimal treatment of these neoplasms remains unclear. A single institution database from a tertiary care cancer center of patients treated for malignant cutaneous adnexal tumors was retrospectively analyzed. Clinicopathologic variables and outcome measures were analyzed in patients undergoing wide excision with or without sentinel node biopsy. 103 patients were analyzed; the majority of tumors were of eccrine sweat gland derivation (n = 69, 70%), and these exhibited a higher rate of nodal involvement and overall worse outcome. Sixteen patients (16%) demonstrated nodal metastasis, which included 10 (10%) with nodal disease at presentation and 6 who developed nodal metastasis during followup. 20 patients underwent sentinel node biopsy, and 2 (10%) had a positive sentinel node. 62% of nodal metastases occurred in patients with porocarcinoma. Seven patients died of disease (7%) with a median time from diagnosis to death of 48 months (range, 10-174). After a median follow up of 44.7 months, age > 70 years and larger tumor size were significantly associated with worse overall survival. Adnexal malignancies are rare tumors, and there is a paucity of information to guide the clinician in determining optimum surgical and medical treatment. Tumors of eccrine derivation, especially porocarcinomas, have a high risk of nodal involvement and may be considered for sentinel node biopsy.

Malignant adnexal tumors of the skin: a single institution experience.

BACKGROUND: Malignant adnexal tumors of the skin (MATS) are rare. We aimed to measure the survival of patients with MATS and identify predictors of improved survival. METHODS: A retrospective review of MATS treated at our institution from 1990 to 2012. RESULTS: There were 50 patients within the time period. Median age was 59.5 years (range 22-95); primary site was the head and neck (52%); most common histologic subtypes were skin appendage carcinoma (20%) and eccrine adenocarcinoma (20%); and the vast majority were T1 (44%). Most patients (98%) underwent surgical treatment. Chemotherapy and radiation were administered to 8 and 14% of patients, respectively. Recurrence rate was 12%. Median OS was 158 months (95% CI, 52-255). OS and recurrence-free survival at 5 years were 62.4 and 47.4% and at 10 years 56.7 and 41.5%, respectively. Five-year and 10-year disease-specific survival (DSS) was 62.9%. Age > 60 years was an unfavorable predictor of OS (HR 12.9, P < .0008) and recurrence-free survival (RFS) (HR 12.53, P < .0003). Nodal metastasis was a negative predictor of RFS (HR 2.37, P < 0.04) and DSS (HR 7.2, P < 0.03) while treatment with chemotherapy was predictive of poor DSS (HR 14.21, P < 0.03). CONCLUSIONS: Younger patients had better OS and RFS. Absence of nodal metastasis translated to better RFS and DSS. Lymph node basin staging is worth considering in the workup and treatment.

Usefulness of 18F-FDG PET/CT for evaluating response of ocular adnexal lymphoma to treatment.

The purpose of this study was to investigate the efficacy of F-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating the ocular adnexal lymphoma treatment responses.We retrospectively reviewed data for 9 histologically confirmed cases of malignant lymphoma. All patients had at least one ocular adnexal tumor site and underwent FDG PET/CT before and after treatment. Patients' histological disease subtypes included diffuse large B-cell lymphoma (n = 3), mucosa-associated lymphoid tissue lymphoma (n = 2), follicular lymphoma (n = 1), NK/T-cell lymphoma (n = 1), lymphoplasmacytic lymphoma (n = 1), and Hodgkin lymphoma (n = 1). The highest FDG uptake by the ocular adnexal lesions was calculated as the maximum standardized uptake value (SUVmax). FDG uptake at ocular adnexal sites and sites of systemic disease after treatment were also assessed using the 5-point Deauville scale.In 1 of the 9 patients, a conjunctival lesion could not be detected by either pre- or posttreatment PET/CT. For 8 of the 9 patients, the SUVmax value at the ocular adnexal site significantly decreased after treatment (7.1 ±â€Š5.1 vs 1.6 ±â€Š0.58; P = .0196). For 7 of the 9 patients, the first posttreatment FDG uptake at the ocular adnexal site was considered a complete metabolic response, and these patients showed an improved clinical ophthalmic presentation with no relapse at ocular adnexal sites during follow-up.FDG PET/CT is useful for evaluation of the response of ocular adnexal lymphoma to treatment, although its usefulness may depend on the histological subtype and site of the lesion.

Microcystic Adnexal Carcinoma and a Summary of Other Rare Malignant Adnexal Tumours.

OPINION STATEMENT: Microcystic adnexal carcinoma (MAC) is a rare, slow-growing, infiltrative malignant tumour most commonly found on the head and neck. It often presents as a solitary skin-coloured or yellow papule, plaque or nodule. Ultraviolet radiation, immunosuppression and ionising radiation are possible risk factors. Clinical and histological differential diagnoses include morpheaform basal cell carcinoma and desmoplastic trichoepithelioma. The diagnosis is usually made by skin biopsy, and the characteristic features are small keratin-filled cysts with nests and cords which resemble ductal structures. Immunohistochemistry can assist in differentiating MAC from other tumours. The local aggressive nature of the tumour and its potential to infiltrate beyond the assessed clinical margins warrant complete excision with marginal control, and we recommend Mohs micrographic surgery. Wide local excision is widely performed but is associated with recurrence given its infiltrative nature and extensive subclinical extension. The role of radiotherapy in the management of MAC is unclear.

Recurrent female adnexal tumor of probably Wolffian origin: A case report.

OBJECTIVE: Wolffian adnexal tumors (WATs) are rare, and metastasis is uncommon. We present the case of a 53-year-old female with a recurrent WAT. CASE REPORT: The patient presented with abdominal distension, and ultrasound revealed heterogeneous echoes (130 × 93 × 116 mm3) around the uterus and ascites. Her cancer antigen 125 (CA125) and CA19-9 levels were elevated. Hysterectomy, bilateral oophorectomy, and tumor resection were performed. The histopathological diagnosis was a WAT. Two years later, multiple abdominal and pelvic masses were found on ultrasonography and computed tomography. Laparotomy revealed nodules in the omentum, mesentery, and pelvic peritoneum. Resection of the pelvic masses and partial resection of the omentum were performed. Immunohistochemistry revealed that the lesions were inhibin A, calretinin, estrogen receptor, progesterone receptor, cluster of differentiation 99, and Pax2 positive. Despite postoperative chemotherapy, she developed liver and renal failure 2 months after surgery, and died of the disease. CONCLUSION: This case further suggests that WATs have malignant potential, and close follow-up is necessary.

Retrospective study of rare cutaneous malignant adnexal tumors of the head and neck in a tertiary care cancer hospital: a case series.

BACKGROUND: Adnexal tumors of the skin are a large and diverse group of benign and malignant neoplasms, which exhibit morphological differentiation toward one of the different types of adnexal epithelium present in normal skin and they pose a diagnostic challenge. The purpose of this study is to share our experience with these rare but aggressive tumors at a tertiary care cancer hospital in a developing country. A retrospective review of 11 patients diagnosed with rare adnexal tumors and their variants from January 2005 to December 2014, treated either surgically or non-surgically, was performed to describe the clinicopathological characteristics and outcome of the disease. CASE PRESENTATION: A total of 11 patients were diagnosed with adnexal carcinoma and its variants: a 34-year-old Sindhi man, a 59-year-old Punjabi woman, a 32-year-old woman from Khyber Pakhtunkhwa, a 43-year-old Punjabi woman, a 64-year-old Punjabi man, a 51-year-old man from Khyber Pakhtunkhwa, a 51-year-old Punjabi woman, a 74-year-old Punjabi woman, a 75-year-old Punjabi man, a 61-year-old man from Khyber Pakhtunkhwa, and a 53-year-old man from Khyber Pakhtunkhwa. The male to female ratio was 1.2:1. The histological variations were sebaceous differentiation (n = 4), microcystic adnexal carcinoma (n = 4), trichilemmal carcinoma (n = 1), pilomatrix carcinoma (n = 1), and hidradenocarcinoma (n = 1). The mean age at presentation was 54 years (range 32 to 75). The primary subsite of involvement was the scalp in nine patients followed by eyelids in two patients. Surgery was the primary treatment modality in almost all patients; postoperative radiotherapy (PORT) was offered to eight patients. The median dose of radiation was 45 Gy to the primary site. Indications for radiotherapy included close margins (n = 2), positive margins (n = 1), high grade histology (n = 4), and multifocal disease (n = 1). On follow-up, two patients presented with local, one regional and two patients developed distant metastasis. CONCLUSIONS: Adnexal carcinomas are rare tumors with diverse histological patterns and a tendency for locoregional and distant metastasis. Surgery should be the mainstay of treatment reserving radiotherapy for adjuvant, palliative, and re-treatment scenarios.

Surgery and Adjuvant Radiation for High-risk Skin Adnexal Carcinoma of the Head and Neck.

OBJECTIVES: Skin adnexal carcinoma (SAC) is a rare cutaneous malignancy that arises from sebaceous and sweat glands. These carcinomas are believed to behave more aggressively than cutaneous squamous cell carcinomas (SCC) with a propensity for local recurrence. The role of adjuvant radiotherapy in SAC is undefined. METHODS: We retrospectively reviewed all cases of head and neck SAC treated with surgery and adjuvant radiation from 2000 to 2012 at a single institution. RESULTS: Nine cases were identified. Median age was 67 (range, 52 to 88) years. The histologies were: adnexal carcinoma (n=1), adnexal carcinoma with sebaceous differentiation (n=1), adnexal carcinoma with squamous differentiation (n=1), skin appendage carcinoma (n=1), sclerosing sweat duct carcinoma (n=1), mucinous carcinoma (n=1), ductal eccrine adenocarcinoma (n=1), porocarcinoma (n=1), and trichilemmal carcinoma (n=1). All tumors were reviewed by a dermatopathologist to confirm the SAC diagnosis.All patients had undergone surgery. Indications for adjuvant radiation included involved lymph nodes (n=4), perineural invasion (n=2), nodal extracapsular extension (n=2), positive margin (n=1), high-grade histology (n=6), multifocal disease (n=2), and/or recurrent disease (n=5). Radiation was delivered to the primary site alone (n=3), to the draining lymphatics alone (n=2), or to both (n=4). One patient received concurrent cisplatin. Median dose to the primary site was 60 Gy and to the neck was 50 Gy.Median follow-up was 4.0 years (range, 0.6 to 11.4 y). Locoregional control was 100%. Five-year progression-free survival was 89%. There was 1 acute grade 3 toxicity and no greater than or equal to grade 2 late toxicities were recorded. CONCLUSIONS: Surgery and adjuvant radiation for high-risk SAC offers excellent locoregional control with acceptable toxicity.

Depth and Patterns of Adnexal Involvement in Primary Extramammary (Anogenital) Paget Disease: A Study of 178 Lesions From 146 Patients.

Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.

Chemotherapy of rare skin adnexal tumors: a review of literature.

Malignant skin adnexal tumors are rare neoplasms which are derived from adnexal epithelial structures of the skin: hair follicle, or sebaceous, apocrine or eccrine glands. Among them, eccrine porocarcinoma is the most frequent, with an aggressive behavior compared to other more common forms of non-melanoma skin cancer. Only few reports describe the treatment of metastatic adnexal tumors, and there is no consensus about the better strategy of chemotherapy. Given the few cases and the absence of randomized clinical trials, it is important to collect clinical experiences on these tumors. Most of these adenocarcinomas are very aggressive and also chemoresistant, and only a targeted-therapy could have an impact on patient survival. Therefore, further studies on the biology of these diseases are necessary. The purpose of the present review is to discuss the treatment of malignant neoplasms of cutaneous adnexae and to suggest some future therapeutic options based on targeted-therapy.

Survival after resection of cutaneous adnexal carcinomas with eccrine differentiation: risk factors and trends in outcomes.

BACKGROUND: Current staging systems do not specifically address cutaneous adnexal carcinomas with eccrine differentiation. Due to their rarity, prognosis and management strategies are not well established. A population-based study was performed to determine prognostic factors and survival. METHODS: Patients diagnosed with cutaneous adnexal carcinomas with eccrine differentiation were identified using the surveillance, epidemiology, and end results population-based cancer registry. Associations between risk factors, treatment modalities, and survival were calculated using logistical regression, Kaplan-Meier estimates and log-rank analysis. RESULTS: The incidence of distinct eccrine subtypes was determined within 1,045 patients with cutaneous adnexal tumors containing eccrine differentiation. All-cause 5-year survival (OS) was 82%, while age-adjusted survival was 94%. Patients with microcystic adnexal carcinoma had improved OS (90%) compared to patients with hidradenocarcinoma (74%), spiradenocarcinoma (77%), porocarcinoma (79%), and eccrine adenocarcinoma (81%). The majority of patients were treated with surgical excision and a small subset with surgery plus radiation, with similar OS. Patients with well-to-moderately differentiated tumors demonstrated improved OS compared to those with poorly differentiated/anaplastic disease. CONCLUSIONS: Histological subtype and grade were associated with survival, and should be specified in biopsies and excised specimens. Surgical excision is appropriate, and the addition of adjuvant radiation may not be associated with survival. These results highlight survival data and high-risk prognostic factors that warrant prospective validation, and may augment current staging systems.

Cutaneous adnexal tumor with an unusual presentation--discussion of a potential diagnostic pitfall.

The clinical presentation of skin adnexal tumors is nonspecific, and histologically; the differential diagnosis between primary cutaneous adnexal malignant carcinomas and metastatic tumors with a visceral origin can be challenging. We report a patient with history of invasive ductal carcinoma of the breast who presented with a 1-cm erythematous palpable lesion on her right calf. The biopsy showed an intradermal proliferation of malignant epithelioid cells with ductal differentiation, histologically compatible with metastatic breast carcinoma. However, the tumor cells labeled strongly and diffusely not only for pancytokeratin and cytokeratin (CK7) but also with p63 and CK5/6; carcinoembryonic antigen highlighted the ductal structures. No labeling was seen for mammoglobin, estrogen/progesterone, Her2-neu, S-100 protein, CK20, thyroid transcription factor-1 (TTF-1), and CDX-2. Based on the p63 and CK5/6 positivity, the differential diagnosis also included the possibility of a primary adnexal neoplasm and a complete excision was advised. The reexcision specimen revealed residual infiltrating dermal tumor and an overlying intraepithelial component with marked cytologic atypia and focal duct formation, diagnostic of a primary cutaneous adnexal tumor with ductal differentiation (porocarcinoma). Immunohistochemical studies (like p63 and CK5/6) can help to differentiate a primary cutaneous neoplasm from a metastatic lesion. This discrimination is of a paramount importance because a diagnostic error can result in profound implications for patient's assumed prognosis and subsequently applied therapy.

Tricoepitelioma desmoplásico múltiple de mejillas: a propósito de un caso / Multiple desmoplastic trichoepithelioma: a case report

El tricoepitelioma es una neoformación benigna diferenciada hacia el folículo piloso. Clínicamente puede presentarse en forma múltiple, solitaria o desmoplásica. Histológicamente plantea algunas dificultades para diferenciarlos del carcinoma basocelular (CSC). Se comunica el caso de una mujer de 28 años de edad y se revisa brevemente la literatura.

Trichoepithelioma is a benign neoformation differentiated from the hair follicle, clinical manifestations can be solitary, multiple or desmoplastic lesions. Histologically, it is not easy to differentiate from basal cell carcinoma. We report the case of a 28-year-old woman, and short review.

Tricoblastoma gigante / Giant trichoblastoma

El tricoblastoma es una neoplasia cutánea benigna con diferenciación hacia células germinativas foliculares y con un estroma densamente fibrocítico que reproduce la papila folicular. Actualmente se utiliza la clasificación de Ackerman et al para denominar este grupo de neoplasias benignas. Generalmente la lesión aparece como un nódulo solitario, con mayor frecuencia en cuero cabelludo y cara, que se enuclea fácilmente durante la extirpación quirúrgica y lo más habitual es que mida entre 1 y 2 cm. Describimos el caso de un tricoblastoma de gran tamaño localizado en nalga

Trichoblastoma is a benign tumour that differentiates towards the hair germ epithelium with a dense fibrous stroma that gives a hair bulb-like appearance. Currently it is being used the classification proposed by Ackerman and colleagues. The lesion usually presents as a solitary nodule, 1-2 cm in diameter, more frequently located on the scalp and face, that is easily removed during surgery. We describe the case of a large trichoblastoma located on the buttock

Female adnexal tumor of probable Wolffian origin diagnosed during the staging evaluation of extranodal diffuse large B-cell lymphoma.

Female adnexal tumor of probable Wolffian origin (FATPWO) is a rare neoplasm arising within the leaves of broad ligament or hanging from it or a fallopian tube. A 55-year-old female patient with the diagnosis of non-Hodgkin lymphoma is presented. The staging procedure revealed a pelvic mass that was not regressed by chemotherapy. Explorative laparotomy showed FATPWO. The extremely rare coexistence of FATPWO in the staging evaluation of non-Hodgkin lymphoma is reported. According to our knowledge, this is the first case of FATPWO coexisting with extranodal diffuse large B-cell lymphoma in the English-language literature.

Malignant transformation within benign adnexal skin tumours.

AIMS: To report five malignant trichogenic tumours arising in longstanding, previously benign adnexal neoplasms through malignant transformation. Malignant trichogenic adnexal tumours are extremely rare neoplasms. METHODS AND RESULTS: The patients were between 55 years and 79 years of age. Three of the tumours were located on the arms, two on the face. Three of our patients had a history of chronic lymphocytic leukaemia, one patient had a history of colonic adenocarcinoma. The duration of the tumour nodules was reported as between 20 and 40 years before sudden changes occurred. These changes included rapid growth, pain, itching, ulceration and bleeding. Histologically, all tumours were well circumscribed and encapsulated. There was a residual benign tumour component and morphological signs such as bone formation, dystrophic calcification and sclerosis suggesting long duration of the lesions. All patients except for one, who refused further clinical investigation due to her advanced age of 79 years, had an underlying systemic malignancy. CONCLUSIONS: The growth stimulus in these benign adnexal neoplasms resulting in malignant transformation may be attributed to the acquisition of additional genetic events or to immunosuppression due to an underlying neoplastic disease. Therefore, patients with systemic diseases or malignancy should be carefully examined and followed for sudden changes in pre-existing benign cutaneous tumours.