Aggressive Digital Papillary Adenocarcinoma Research Articles

National epidemiology of digital papillary adenocarcinoma in England 2013-2020: a population-based registry study.

Digital papillary adenocarcinoma (DPA), formerly known as aggressive DPA, is a rare adnexal cancer of sweat gland differentiation with metastatic potential. DPA epidemiology and patient outcome data are a prerequisite to develop diagnostic and therapeutic guidance, which is lacking for this rare cancer. To report the incidence, patient demographics and treatment of patients with DPA in England from 1 January 2013 to 31 December 2020 using national cancer registry data. DPA diagnoses in England during 2013-2020 were identified from the National Cancer Registration Dataset using morphology and behaviour codes. These were registered from routinely collected pathology reports and cancer outcomes and services datasets. The 2013 European age-standardised incidence rates (EASRs) were calculated. In total, 36 DPA (7 in females and 29 in males) were diagnosed. The median age at diagnosis for the cohort was 54 years (interquartile range 46-64). The most frequently affected sites were upper limbs (81%). All patients in the cohort received surgical excisions. The European age-standardised incidence rate (EASRs) was 0.10 [95% confidence interval (CI) 0.07-0.14] per 1,000,000 person-years (PY)]. This study reports the incidence and variation of DPA in England between 2013 and 2020. DPA was more common in older men and predominantly affected the upper limbs. This supports the need to develop a national policy for the reporting and management of DPA as well as clinical guideline development.

DP24 A case of digital papillary adenocarcinoma linked to human papillomavirus-42

Abstract A 60-year-old man with known stage-4 non-small cell lung cancer (NSCLC) and previous right-thumb hidradenoma presented with a 5-month history of a growing vascular lesion on his right great toe. Histology revealed a digital papillary adenocarcinoma (DPA) and positive quantitative polymerase chain reaction (qPCR) for human papilloma virus (HPV)-42 (courtesy of Thomas Wiesner’s research team in Austria). Review of previous histology for the lung and thumb lesions showed histological features consistent with DPA. He re-presented after 2 years with metastatic DPA in his right posterior calf. Following wide local excision (WLE), this locally reoccurred, requiring further excision. Aside from chemotherapy for NSCLC, he was not immunosuppressed and had no history of HPV-related disease. Digital papillary adenocarcinoma is a rare and aggressive neoplasm of sweat glands. Despite being a low-grade tumour, the rates of metastases and reoccurrence are high. Distant metastases are common and can present years after initial presentation. Distant metastases without lymph node spread have been reported. The annual incidence in the USA is ~0.08 cases per 1 000 000, typically presenting in men aged 50–70 years as a solitary lesion on the digits. It can invade muscle, tendons and bone. Owing to its rarity, misdiagnosis and treatment delay are common (Kobayashi T, Hiura A, Oishi K et al. Aggressive digital papillary adenocarcinoma with multiple organ metastases: a case report and review of the literature. Am J Dermatopathol 2016; 38:910–14). Studies show a link between HPV-42 and DPA, with qPCR detecting HPV-42 in known DPA cases (HPV-42 negative in hidradenoma). Human papilloma virus-42 was previously unknown to be oncogenic, and HPV vaccines do not target HPV-42 (Leiendecker L, Neumann T, Jung PS et al. Human papillomavirus 42 drives digital papillary adenocarcinoma and elicits a germ cell-like program conserved in HPV-positive cancers. Cancer Discov 2022; 13:70–84). There are no clear management guidelines and no drug therapy for DPA. Case studies have shown chemotherapy to be ineffective. Management is surgical with either amputation or WLE to avoid reoccurrence or metastases (Leiendecker et al.). Clinical suspicion for DPA should be high given its aggressive nature with regular long-term follow-up to detect reoccurrence or metastases early. More research is required on the epidemiology of this rare tumour in the UK and Europe and on treatment strategy beyond surgical resection, targeting the link between HPV-42 and DPA.

Aggressive Digital Papillary Adenocarcinoma Mimicking a Giant Cell Tumour – A Case Report and Review of the Literature

Aggressive digital papillary adenocarcinoma (ADPAca) is a rare, underreported, and often misdiagnosed malignant tumour of the eccrine sweat gland, with high recurrence and metastatic potential. We present a case of a painless mass over the middle phalanx of the dominant index finger in a 51-year-old man. The mass was present for over 20 years, which had slowly increased in size. The patient only presented when it began to interfere with his profession as an electrician. The clinical presentation was consistent with a giant cell tumour. Histological diagnosis was of an ADPAca. Staging investigations were negative and he subsequently went on to have a ray amputation. The importance of high clinical suspicion of digit lesions is highlighted. No specific histologic features have been identified to predict recurrence or metastasis. We review the merits of performing sentinel node biopsy and alternative treatment options such as Moh’s micrographic surgery. We review the international literature to assess metastatic potential and follow-up requirements.

Modified ketogenic diet in solid tumors: A Veteran Affairs Pittsburgh Healthcare System case series.

e14217 Background: Cancers prefer glucose due to mitochondrial dysfunction. Ketogenic diets fuel normal cells while starving cancer. Sparse data exists on ketogenic diets in solid tumors. Methods: Studied 5 advanced solid tumor patients on a modified ketogenic diet plus standard of care chemotherapy. Daily carbohydrate limited to 20-40 grams, no sweets or starch. Histories and clinical courses are presented. Results: Case 1: 70 year old male, medically inoperable Stage IIIA poorly differentiated squamous cell lung cancer and non-hodgkins lymphoma. Treated with radiation and paclitaxel/carboplatin. After 5 months, lung cancer relapsed in a neck mass, treated with chemoradiation plus the diet. At 46 months, scans and blood counts were normal. Case 2: 42 year old, 417 lb. male diabetic stage IV colon cancer, spread to lungs and liver. Progressed on 5FU/bevacizumab/oxaliplatin, irinotecan, tipiracil/trifluridine, regorafenib but responded to 5FU/irinotecan rechallenge plus liver chemoembolization. Dieted, mild ketosis but lost 64 lbs, stable disease at 6.5 years. Case 3: 42 year old male, Stage III BRAF V600 E melanoma, Vemurafenib intolerant. Bulky axillary nodes resected plus diet for 3 years. Complete remission at 7 yrs 9 months. Case 4: 57 year old male, medically inoperable liver cancer, normal AFP values and normal scans after 5 months of sorafenib. AFP later increased to 690 ng/ml. Advised to change treatment but he refused and started the ketogenic diet with the sorafenib. After 5 months, AFP improved to 445 ng/ml. Sorafenib and diet interrupted for 3 months, AFP rose to 1017. At 7 yrs, 4 months, back on sorafenib and diet, AFP 1520 mg/ml, negative scans. Case 5: 49 year old male, aggressive digital papillary skin adenocarcinoma, multi-organ metastases. Had side-effects with many chemotherapies (paclitaxel/bevacizumab/carboplatin, sorafenib, gemcitabine, oxaliplatin/5FU, cyclophosphamide) Stable disease on diet despite multiple therapy changes. At 34 months, he was off the diet, tumors grew plus new brain lesions (resected). Alive on atezolizumab at 36 months. Conclusions: Ketogenic diets in human solid tumors seem well tolerated and may improve response and survival after standard therapy.

Is aggressive digital papillary adenocarcinoma really aggressive digital papillary adenocarcinoma?

Citation: Chen S, Asgari M. Is aggressive digital papillary adenocarcinoma really aggressive papillary adenocarcinoma? Dermatol Pract Concept. 2014;4(3):5. https://dx.doi.org/10.5826/dpc.0403a05

Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma.

Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001). The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.

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

As a rare cutaneous malignancy, epidemiologic and outcomes data for aggressive digital papillary adenocarcinoma (ADPA) are limited and no treatment guidelines exist. To provide a population-based study of ADPA incidence and outcomes with a subgroup comparison of patients with localized versus regional disease. 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. 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. 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.

Aggressive Digital Papillary Adenocarcinoma

We report an interesting case of aggressive digital papillary adenocarcinoma (ADPCA), a rare eccrine neoplasm with high rates of recurrence and metastatic potential. Diagnosis and treatment is often delayed due to its unusual clinical presentation and it may be confused with other benign lesions. A man aged 71 was referred to the medical oncology clinic with CT scans showing recurrent oligometastatic ADPCA. Initial trauma more than a decade ago to the fourth digit lead to recurrent swelling necessitating a biopsy and subsequent amputation. Routine imaging surveillance then showed recurrence in the axillary lymph nodes for which the patient underwent an axillary node clearance. His most recent scan now shows a growing metastatic pulmonary nodule which is in consideration of resection. There is limited documentation on management of such cases. It is also important not to overlook the possibility of ADPCA when a patient presents with recurrent digital swellings or lesions.

Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19 cases

Aggressive digital papillary adenocarcinomas (ADPA) are malignant tumors of sweat glands having recurrence/metastatic potential. We sought to describe the clinical/histopathological characteristics of a series of ADPA. This is a retrospective case series of 19 ADPA. The tumors occurred in 17 men and 2 women (mean age: 47years). They involved digits (15), big toe (3), andpalm (1), and measured from 3 to 30mm. They were mostly solid and cystic, with papillary projections and tubular structures. Atypia was mostly mild to moderate. Tumors tested positive for p63, keratin 7, keratin77 (eccrine duct-specific), PHLDA1, and epithelial membrane antigen in most cases, andfor carcinoembryonic antigen, smooth muscle actin, S100 protein, estrogen, progesterone, and androgen receptors in 50%. Mean Ki67 proliferation index was 15%. Local recurrence was observed in 4 cases. One patient had axillary lymph node metastasis. Histopathologic parameters were not predictive of evolution. Conservative surgical treatment, performed in 7 of 19 cases, did not result in more recurrences than amputation. The study was retrospective and the number of cases is small. ADPA are histologically variable, but papillary projections are always present. Keratin 77 expression suggests an eccrine origin. P63 is helpful to exclude metastasis. Conservative surgery may be sufficient in some cases.

Papillary adnexal neoplasm (aggressive digital papillary adenocarcinoma) on the ankle of a 15‐year‐old girl: case report and review of literature from a pediatric perspective

Digital papillary adenocarcinoma is a rare malignant tumor of the sweat glands, most commonly encountered in adult males. Only few pediatric cases have been reported, with an apparent predominance of females and none on the ankle. We report a case of a 15-year-old girl with a slowly growing, non-tender mass on the right ankle presenting with difficulty in walking; clinically believed to be a keloid. Excision of the mass revealed a glandular neoplasm with largely eccrine and focally apocrine differentiation. Histologic features do not reliably predict biologic behavior. Because of the existing confusion over the nomenclature, we propose that such tumors be called 'papillary adnexal neoplasms of distal extremities'.

Aggressive Digital Papillary Adenocarcinoma in a Young Female—a Rare Presentation

A 20 year old female presented with a recurrent soft tissue swelling over the medial aspect of proximal phalanx of left little finger. It had recurred one year after excision. There was no lymphadenopathy or bony involvement. Previous histopathology reports were not available. After excision histopathological diagnosis was aggressive digital papillary adenocarcinoma. Later Ray's amputation of little finger was planned. Aggressive digital papillary adenocarcinomas are rare sweat gland tumors which occur on hands, fingers, and toes. They have high local recurrence rate and may metastasize to lungs and lymph nodes.

Next-generation sequencing reveals rare genomic alterations in aggressive digital papillary adenocarcinoma.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare cutaneous adnexal neoplasm that occurs on the fingers, toes, palms, and soles. It is characterized by aggressive biological behavior, with a relatively high potential for local recurrence (30%-40% of cases) and distant metastasis (up to 14%). This retrospective study assessed the mutation status of ADPA lesions to identify possible therapeutic targets. We performed comprehensive genomic profiling of 9 ADPA cases that had been identified in our database. We identified a BRAF-V600E (BRAF c.1799T>A p.V600E) mutation in 1 patient (11%). Complete surgical excision is the treatment of choice for ADPA; however, there are no uniform diagnostic guidelines or recognized effective treatments for metastasis, and no therapeutic targets have been identified. Targeted therapy may be a treatment option for patients with metastatic ADPA if a relevant oncogene mutation is identified. Further studies with a larger sample size are required to confirm our findings and identify more molecular mechanisms.

Aggressive digital papillary adenocarcinoma - a rare malignant tumor of the sweat glands: two case reports and a review of the literature.

Aggressive digital papillary adenocarcinomas are rare malignant tumors often located on the digits of the hand. Due to lack of pain, slow growth, and an inconspicuous appearance, diagnosis is often missed or delayed. We report two cases and review the present literature to give recommendations for diagnosis and treatment.

Digital papillary carcinoma.

Digital papillary carcinoma (DPC) is a rare, slow growing, malignant tumor with eccrine differentiation that occurs predominantly in digits. This tumor was originally classified as a benign neoplasm; aggressive digital papillary adenoma (ADPA) was first described by Helwig in 1979 [1]. In 1987, Kao et al. [2] classified ADPA and aggressive digital papillary adenocarcinoma (ADPAca) based on differences in histologic findings. However, a recent retrospective study revealed that neither histologic nor clinical characteristics were predictive of recurrence or metastasis [3]. Therefore, the designations “ADPA” or “ADPAca” should be reevaluated because lesions with benign histologic features have both recurred and metastasized [3]. In the 2006 World Health Organization (WHO) classification, ADPA or ADPAca were grouped under a single entity of DPC without any benign counterpart [4]. We report a case of DPC on the third finger that lasted for 20 years, but increased in size and became extremely painful in the past 7 months. After a complete excision, no recurrence or metastasis was found for two and a half years. A brief review of the literature is presented.

A slowly enlarging mass on the finger

An otherwise healthy 71-year-old woman presented with an asymptomatic mass on her right 4th finger that had been slowly enlarging over the past 2 years. On physical examination, there was a tan-pink, freely mobile, rubbery 9-mm papule with a central keratotic plug located over the extensor aspect of the proximal interphalangeal joint of the right 4th finger. A 3-mm punch biopsy of the lesion was performed. Histopathologic findings were consistent with a diagnosis of aggressive digital papillary adenocarcinoma (ADPAca), an adnexal tumor with high metastatic potential that is unfortunately commonly misdiagnosed owing to its rarity and nondescript appearance. Aggressive surgical treatment including radical excision or digital amputation with or without sentinel lymph node biopsy is advocated in the treatment of ADPAca.

Papillary eccrine adenoma should not be mistaken for aggressive digital papillary adenocarcinoma

Papillary eccrine adenoma should not be mistaken for aggressive digital papillary adenocarcinoma

Perilipin and adipophilin expression in sebaceous carcinoma and mimics

Although adipophilin has been reported to be a sensitive marker for sebaceous carcinoma, others have noted its expression in squamous cell carcinoma and a variety of noncutaneous tumors, suggesting that lipid droplet accumulation is a frequent feature of neoplastic cells. We investigated the expression of adipophilin and perilipin in 101 cutaneous carcinomas. They included 30 cases of sebaceous carcinoma, 28 squamous cell carcinoma with clear cell change (18 invasive and 10 in situ tumors), 8 hidradenocarcinomas, 1 spiradenocarcinoma, 10 porocarcinomas, 4 malignant chondroid syringomas, 1 malignant cylindroma, 7 apocrine carcinomas, 6 eccrine carcinomas, 5 aggressive digital papillary adenocarcinomas, and 1 pilomatrical carcinoma. Adipophilin stained the rim of cytoplasmic lipid droplets in various tumor types, including sebaceous carcinomas (30/30, 100%), squamous cell carcinoma with clear cell change (21/28, 75%), and eccrine-apocrine carcinomas (25/43, 58%). On the other hand, perilipin expression was seen in 13 (43%) of 30 sebaceous carcinoma and only 1 hidradenocarcinoma. The remaining 28 squamous cell carcinomas with clear cell change and 42 eccrine-apocrine carcinomas were negative. Although specific for invasive sebaceous carcinoma, perilipin expression was not helpful in distinguishing sebaceous carcinoma in situ from squamous cell carcinoma in situ with clear cell change. The expression of adipophilin seen in variety of cutaneous tumors suggests that the biosynthesis of lipid is altered in these neoplasms.

Cutaneous Digital Papillary Adenocarcinoma

Aggressive digital papillary adenocarcinoma is a rare tumor predominantly involving the distal end of digits. We examined 31 cases of this distinctive tumor for clinicopathologic, immunohistochemical, and follow-up data where available. Males were predominantly affected (n=29), with a mean age of 43 years (range, 14 to 67 y). Three lesions were reported in patients below the age of 20 years. All cases involved a finger (n=26) or a toe (n=5), with most involving the distal portion of the digit (n=29). Two lesions involved the base of the digit/webspace. Histopathologically, all tumors involved the dermis with subcutaneous extension in 14 cases. The lesions demonstrated a multinodular solid and/or cystic pattern, with focally infiltrative architecture in 21 cases. Papillary projections were: prominent (n=10), focal (n=15), or not identified (n=6). Within the solid component, tubular structures were present at least focally in all cases. Cytologic atypia ranged from mild (n=8) to moderate (n=20), but was focally severe in 3 cases. Mitotic count ranged from <1 to 18 per mm. Focal necrosis was seen in 6 cases. Immunohistochemically stained sections were available for review in 8 cases. Tumor cells were diffusely positive for MNF116 (3 of 3). Carcinoembryonic antigen and epithelial membrane antigen highlighted the luminal border of tubules (8 of 8). Smooth muscle actin (5 of 6) and calponin (6 of 6) highlighted a myoepithelial layer around tubular/glandular structures, as did p63 (2 of 2) and podoplanin (5 of 5). Follow-up after excision or amputation (n=23; range, 2 mo- to 21 y) revealed local recurrence (n=5) and metastatic disease (n=6; lymph node in 1, lungs in 4, and both lymph node and lung in 1). Metastases were noted at presentation in 2 cases (lymph node in 1 and lung in 1), but presented as late as 14 and 20 years in lymph node and lung, respectively. Only 1 patient died of metastatic disease 6 years after initial diagnosis, after multiple recurrences and lung metastases. Three patients were alive with progressive disease up to 24 months after developing lung metastases. Histopathologic features were not found to be predictive of outcome. The presence of tumor-associated myoepithelial cells histologically and immunohistochemically was not synonymous with benignity. Wide excision and partial digit amputation significantly reduced recurrence and metastatic rates. Delayed occurrence of metastases and a protracted course despite metastatic disease, necessitates long-term follow-up. As the name implies a malignant neoplasm, the rubric "aggressive" is unnecessary.

Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest.

The Medial Plantar Flap Vascularized by the Reverse Flow Lateral Plantar Artery: A Novel Variation through the Case of Aggressive Digital Papillary Adenocarcinoma of the Sole

Aggressive digital papillary adenocarcinoma (ADPA) is a rare neoplasm of eccrine sweat gland origin that typically presents as a mass on the distal extremities. It is associated with high rates of local recurrence and distal metastasis. Presented here is the case of a 61-year-old male who developed ADPA on his distal sole just above the head of the first metatarsal bone. Wide excision of the tumor involving a 3-cm skin margin from previous surgical scar of biopsy was performed, and sentinel lymph node biopsies were taken from the popliteal fossa and inguinal regions. During this wide excision surgery, the pedicle for the reverse medial plantar flap had to be removed along with the tumor. Reconstructive surgery was performed with a medial plantar flap that was vascularized with a lateral plantar artery in a reverse fashion. This flap successfully covered the defect and the patient can walk without any problems. However, the pedicle crossed the donor site somewhat tightly and the flap became congested for a while. Therefore, it is important to ensure careful handling of the donor site when performing this procedure.