Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.

Hidradenocarcinoma: A Case Series From the Scripps Clinic With a Systematic Review of the Literature.

BACKGROUND: Hidradenocarcinoma (HAC) is a rare adnexal carcinoma. To the best of the authors' knowledge, there are no published systematic reviews on HAC. OBJECTIVE: To incorporate a case series from the authors' institution and systematically integrate reported information to provide a reference tool for optimization of diagnosis and management. METHODS: A comprehensive MEDLINE search was conducted from database inception to 2021 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This yielded 225 studies with 165 cases of HAC. References of included articles were also searched. In addition, 9 patients with HAC were identified from the authors' institution over the past 10 years. RESULTS: The mean age of HAC presentation is 60 years with a slight male predilection (60%). The head and neck is the most commonly affected region. Over 36% of cases either presented with metastatic disease or went on to metastasize. The most common treatment type was wide local excision, followed by Mohs micrographic surgery. CONCLUSION: Early detection with accurate histologic interpretation is prudent in all cases of HAC. Wide local excision is the current first-line treatment. However, Mohs micrographic surgery offers complete marginal analysis with evidence of reduced risk of metastasis and better outcomes compared with wide local excision. Currently, there are no National Comprehensive Cancer Network guidelines for the treatment of HAC, and consensus guidelines are limited to tumor and nodal metastasis staging provided by the American Joint Committee on Cancer, eighth edition. Thus, this case series and systematic review integrates important aspects of diagnosis, workup, and management of HAC.

Porocarcinoma: Clinical and Histological Features, Immunohistochemistry and Outcomes: A Systematic Review.

Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.

[Management of malignant adnexal neoplasms of the skin]. / Management von malignen Adnextumoren der Haut.

Malignant adnexal neoplasms of the skin are a heterogeneous group of rare malignancies with eccrine, apocrine, sebaceous and follicular differentiation. Essential clinical practice recommendations for the overall management of these cancers are presented. Moreover, specific evidence-based findings according to diagnosis, therapy and follow-up of porocarcinoma, sebaceous carcinoma and microcystic adnexcarcinoma will be explained.

Apocrine hidrocystoma: a slowly growing postauricular translucent nodule.

Apocrine hidrocystoma is a benign, cystic proliferation of the apocrine sweat gland that may present commonly on sun-exposed areas of the head and neck. However, given its location and features, apocrine hidrocystomas may often be confused with malignant tumors such as basal cell carcinomas or primary cutaneous mucinous carcinomas. Herein, we present an unusual case of an apocrine hidrocystoma presenting in the postauricular region and highlight the importance of histopathological examination of cystic tumors on the periauricular area.

Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.

Pure invasive apocrine carcinoma is a rare type of primary breast cancer, constituting ~1% of all breast cancers. Since most pure invasive apocrine carcinomas are triple negative, the lack of targeted therapies for triple-negative breast cancer has fostered efforts to discover actionable molecular targets in these tumors. In this study, we analyzed the clinicopathologic characteristics and comprehensive genomic profiling of 18 patients with pure triple-negative apocrine carcinomas (TNACs) using a 324-gene panel assay (FoundationOne CDx). The median age of these patients was 55.5 years, and the postmenopausal status rate was 77.8%. In total, 83.3% of patients were diagnosed with histological grade II, and 16.7% were diagnosed with grade III. The majority of patients presented at an early tumor-node-metastasis (TNM) stage (I: 38.9%; II: 50.0%; and III: 11.1%). The mean Ki-67 index was 9.7%, and the percent of PD-L1 positivity was 11.7%. With a median follow-up period of 76.5 months, one patient died, and two experienced distant metastases. There were 61 clinically relevant genomic alterations among all 18 pure TNACs, and the mean tumor mutation burden (TMB) was 3 Mut/Mb. The top ranked altered genes were PIK3CA (72.2%), PTEN (33.3%) and TP53 (27.8%). There were four novel mutations found in PTEN and an actionable rearrangement involving FGFR2-TACC2 that has not been reported in breast cancer before. In total, 88.9%, 50%, 44.4%, and 16.7% of TNACs had at least one clinically relevant genomic alteration in genes involved in the PI3K/mTOR, cell cycle, RAS/RAF/MEK and growth factor receptor-related pathways, respectively. All patients had at least one clinically relevant genomic alteration, and 94.4% had at least one actionable alteration. To the best of our knowledge, this study is the largest genomic sequencing cohort of pure TNACs. Incorporation of comprehensive genomic profiling into TNACs might shed light on potential therapeutic opportunities for both targeted drugs and immune checkpoint inhibitors.

Comparative Efficacy of Hidrocystoma Treatments: A Systematic Review.

INTRODUCTION: Although various treatment options for hidrocystomas have been described, the comparative efficacy of these treatments is poorly understood. METHODS: We conducted a systematic review of all articles describing the treatment of hidrocystomas. Treatment modalities were categorized as destructive surgical procedures, skin-directed therapies, systemic medical therapies, general measures, or combined. Patient and tumor characteristics, as well as response rate, recurrence rate, and adverse effects, were extracted from each article. RESULTS: A total of 94 articles involving 192 patients and 255 unique treatment events were included in the final analysis. Destructive surgical procedures had an overall response rate and recurrence rate of 92.9% and 10.8%, respectively. Skin-directed therapies had an overall response rate of 72.6%. The overall response rate to systemic medical therapies was 71.4%. Solitary hidrocystomas were primarily treated with destructive surgical procedures, including excision, which was associated with a 4.7% recurrence rate. Multiple hidrocystomas were successfully treated with a variety of therapies, including destructive surgical procedures and skin-directed therapies requiring ongoing or repeated therapy. CONCLUSIONS: Excision has the highest efficacy for solitary hidrocystomas. A number of therapies have shown efficacy for multiple hidrocystomas, including lasers, intracystic trichloroacetic acid, intracystic hypertonic glucose, topical and oral anticholinergics, and botulinum toxin. Aluminum chloride is associated with a low response rate. Larger comparative studies are needed to further evaluate the optimal treatments for solitary and multiple hidrocystomas.

Treatment of a case with giant eyelid syringomas.

He had a history of multiple asymptomatic flesh-colored papules, which had slowly increased in number and coalesced into plaques, on both upper and lower eyelids. Some of the plaques were giant and mostly coalescent in nature. We excised surgically the giant plaques which were approximately 1.5-2 cm in diameter symmetrically from upper and lower eylids and the remaining plaques were left to be treated with cauterization. Histopathological examination revealed syringoma. Both of the eyelids were observed to have a cosmetically adequate appearence after the surgical intervention.

Prognostic factors and survival outcomes for head and neck cutaneous adnexal cancers.

OBJECTIVES: Malignant cutaneous adnexal tumors (MCAT) are rare and comprise a heterogeneous group of cancers. There have been several studies reviewing prognostic factors of these tumors, but no studies focusing on the head and neck. This study aimed to review a large population based database to evaluate prognostic factors that could impact survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify patients with MCAT of the head and neck. Both overall and disease specific survival were the main outcome measures for the study. Univariate and multivariate analyses were performed to evaluate the association of suspected prognostic factors with survival. RESULTS: The five-year OS and DSS were 72.6 and 95.5%, respectively. A favorable factor for OS was surgical resection ([HR] 0.324; P = 0.001), while unfavorable factors for OS include older age (1.051; P < 0.001), higher tumor grade (1.254; P = 0.049), larger tumor size (1.293; P = 0.003), and positive nodal involvement (3.323; P = 0.002). A favorable factor for DSS was surgical resection (0.026; P < 0.001). Unfavorable factors for DSS include older age (1.058; P = 0.046), larger tumor size (2.528; 1.565-4.085; P < 0.001), and positive nodal involvement (4.761; P = 0.022). CONCLUSION: Review of the SEER database shows good 5-year OS and DSS rates, similar to those cited in other studies. We identified several prognostic factors associated with survival, while histologic sub-type does not seem to be associated with survival. Surgical resection is the mainstay of treatment.

Eccrine Porocarcinoma: New Insights and a Systematic Review of the Literature.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare cutaneous neoplasm with high potential for morbidity and mortality. Due to its rarity, there is a paucity of data profiling diagnosis, work-up, and management. OBJECTIVE: To consolidate reported information on demographics, diagnostics, clinical behavior, treatment modalities, and patient outcomes in EPC to provide a reference tool to optimize diagnosis and management. METHODS: A comprehensive PubMed search was performed from 1963 to November 2017 using PRISMA guidelines. This yielded 155 articles detailing 206 cases of porocarcinoma. RESULTS: Eccrine porocarcinoma most often presents in elderly patients on the head and neck or lower limbs. Metastatic disease at presentation is not uncommon (22%). Primary tumor location is significantly correlated with presence of metastasis (p = .038). The most common treatment is excision followed by Mohs micrographic surgery (MMS), although the outcomes after MMS were superior to those after surgical excision. CONCLUSION: This systematic review of individual patient data reveals that all patients should have a histological diagnosis with imaging considered for high-risk cases. Primary tumor location should also be considered in diagnostic and therapeutic decision-making. Although wide local excision (WLE) is currently the first-line treatment, MMS is becoming increasingly used, with evidence indicating improved outcomes as compared to those seen with WLE.

Aggressive Digital Papillary Adenocarcinoma: Population-Based Analysis of Incidence, Demographics, Treatment, and Outcomes.

BACKGROUND: As a rare cutaneous malignancy, epidemiologic and outcomes data for aggressive digital papillary adenocarcinoma (ADPA) are limited and no treatment guidelines exist. OBJECTIVE: To provide a population-based study of ADPA incidence and outcomes with a subgroup comparison of patients with localized versus regional disease. METHODS: Data from 18 registries within the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were examined for patients with ADPA (1995-2013) to provide demographic- and cancer-related information, and to calculate race- and age-specific rate ratios, incidence, and mortality. Patients were stratified by the stage for further comparison. RESULTS: Ninety-four cases of ADPA were identified. Overall, ADPA incidence was 0.08 per 1,000,000 person-years, 4 times higher in males than in females (0.13 vs 0.03, p < .001), and most common in Caucasians. Regional disease spread occurred in 22.3% of patients and disease-specific mortality in 2.1% of patients. Patients with regional versus localized disease at diagnosis did not differ significantly in sex, age, race, primary site, tumor size, or mortality. CONCLUSION: Aggressive digital papillary adenocarcinoma is a rare malignancy with increasing incidence. Regional disease spread is not infrequent, but mortality is rare. Identification of patients best suited for additional diagnostic procedures or more extensive surgical resection remains challenging.

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.

A case and literature review of orbital microcystic adnexal carcinoma.

Microcystic adnexal carcinoma (MAC) is a very rare and locally aggressive sweat gland tumour. MAC has been well reported presenting as a periocular cutaneous lesion, rarely with subsequent direct orbital invasion and only once as a primary orbital lesion. Local recurrence is frequent after primary surgical excision and the role of adjuvant radiotherapy is ill-defined. We describe a case of orbital MAC treated successfully with radiotherapy after incomplete margin clearance post exenteration surgery and review the associated literature.

[Multiple eccrine hidrocystomas on the lower forehead and nose of a 60-year-old man]. / Multiple ekkrine Hidrozystome an Stirn und Nase eines 60-jährigen Mannes.

Multiple eccrine hidrocystomas are benign cystic skin lesions which originate from the sweat gland ducts and typically affect women's midfacial area. Sweating may lead to an increase in size of the translucent papules. In some cases hidrocystomas are associated with other diseases such as Parkinson's disease. Treatment options include laser, topical and systemic anticholinergic drugs (glycopyrrolate, clonidine, atropine, and oxybutynin), whereby therapeutic success is limited in most cases.

[Hidradenocarcinoma of the heel associated with inguinal metastases]. / Hidradénocarcinome du talon associé à des métastases inguinales.

BACKGROUND: Hidradenocarcinoma is a rare malignant tumour involving the sweat glands. It classically arises de novo, only rarely resulting from pre-existing hidradenoma. The literature contains few reports of lymph node metastasis in this tumour. We report a case of a patient with hidradenocarcinoma of the heel associated with inguinal node metastases. PATIENTS AND METHODS: We report the case of a 64-year-old patient with a history of chronic smoking, who in the last two years developed a painless nodule in his right heel, with no prior injury, and which gradually increased in size to become an ulcerated tumour. Physical examination revealed a rounded tumour mass, ulcerated in the centre, and associated with multiple inguinal adenopathies. Histological and immunohistochemical examination was suggestive of hidradenocarcinoma. The patient had undergone extensive local excision with inguinal lymphadenectomy. Histological examination showed infiltration of lymph nodes by the tumour with capsular rupture. Radiotherapy was subsequently given. The outcome was good without recurrence after 34 months of follow-up. DISCUSSION: Hidradenocarcinoma is a rare malignant tumour. Diagnosis is based on histological and immunohistochemical examination. However, hidradenocarcinoma may on occasion be difficult to differentiate from hidradenoma, a benign tumour, hence the interest of complete surgical resection with safety margins even in the absence of cytological malignancy. Local recurrences are common. The occurrence of lymph node metastasis during hidradenocarcinoma has been described only rarely in the literature. Such metastases usually occur after tumour resection. The specific features of our case are the rarity of lymph node metastases in hidradenocarcinoma coupled with the fact that these metastases were discovered upon diagnosis of the primary tumour.

Eccrine Porocarcinoma: Patient Characteristics, Clinical and Histopathologic Features, and Treatment in 7 Cases. / Porocarcinoma ecrino: aspectos demográficos, clínicos, histopatológicos y terapéuticos en una serie de 7 pacientes.

Eccrine porocarcinoma is a rare, malignant cutaneous adnexal tumor that arises from the ducts of sweat glands. Found mainly in patients of advanced age, this tumor has diverse clinical presentations. Histology confirms the diagnosis, detects features relevant to prognosis, and guides treatment. Growth is slow, but the prognosis is poor if the tumor metastasizes to lymph nodes or visceral organs. We report 7 cases of eccrine porocarcinoma, describing patient characteristics, the clinical and histopathologic features of the tumors, and treatments used. Our observations were similar to those of other published case series. Given the lack of therapeutic algorithms or protocols for this carcinoma, we propose a decision-making schema based on our review of the literature and our experience with this case series. The algorithm centers on sentinel lymph node biopsy and histologic features.

Evaluation and management of the patient with multiple syringomas: A systematic review of the literature.

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma ("tadpole") shaped tail comprised of dilated, cystic eccrine ducts. Clinically, syringomas typically present in adolescent females predominantly in the periorbital region. They may present as solitary or multiple lesions, and more rare sites of involvement include the genitals, palms, scalp, and the chest. Over the past 50 years, there have been >800 reported cases of syringoma either alone or in conjunction with a systemic syndrome, most commonly Down syndrome. The primary aim of this systematic review is to discuss the clinical features and associations of syringomas with a focus on the patient with multiple syringomas. Its secondary aims are to explore pathophysiology with a focus on multiple syringomas and provide comprehensive data on both traditional and novel treatments. Importantly, multiple syringomas present across a broad clinical spectrum. Though noted in many textbooks to be related to tumor syndromes, the association of syringomas with inherited tumor syndromes is only rarely reported in the literature. Despite multiple reported cases of syringoma, the pathophysiology remains poorly understood and treatment continues to pose a significant challenge.

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.