Digital papillary adenocarcinoma.

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.

Digital papillary adenocarcinoma (DPAC) is a rare, low-grade sweat gland carcinoma primarily found on the hands, fingers, or toes and predominantly affecting males. Distinguishing DPAC from benign sweat gland tumors can be challenging. We present the case of a 52-year-old patient with a progressive tumor on the finger initially misdiagnosed as a viral wart. Histological examination revealed a cytologically basophilic sweat gland tumor with tubular structures, papillary protrusions, and a characteristic immunohistochemical staining pattern for CK 7 and Actin. HPV-42 positivity and molecular analysis confirmed the diagnosis of DPAC. HPV-42 has been strongly associated with DPAC. Additionally, p16 positivity and BRAFV600E negativity were observed. These findings aid in the differential diagnosis of acral sweat gland tumors and guide clinical management, including with respect to the potential for recurrence and metastasis.

Digital papillary adenocarcinoma (DPA ) is a rare malignant neoplasm of sweat glands, which was first described by Helwig in 1979 and then classified by Kao in 1987. This disease most often occurs in men aged 50–70 years and is characterized by a relatively favorable prognosis. In most cases, radical excision of the tumor leads to cure. However, 14–47 % of patients develop distant metastases with predominant lung involvement (70 %). The study of etiology and pathogenesis of this rare cancer and its molecular genetic profile seems to be interesting. Currently, there is no clear approach to the treatment of metastatic DPA , but sporadic cases of using chemotherapy have been reported. Aim of the study: to analyze current data on the pathogenesis of DPA , diagnostic features and treatment methods used, as well as to present the first clinical case of treatment of disseminated digital carcinoma with immune checkpoint inhibitors described in scientific literature. Material and Methods. A search of available literature published in Medline, Pubmed, etc. databases from 1984 to 2023 was performed, 21 sources were included in this review. Clinical Case Description. We present a rare case of metastatic digital papillary carcinoma in a 23-year-old male with disease manifestation at the age of 14 years. Lack of vigilance and awareness of oncologists and morphologists did not allow timely diagnosis of malignancy, even in case of 3 local recurrences of the disease. Only biopsy of a metastatic lung nodule with histological and IHC examination (of archival and new material) made it possible to make a correct diagnosis. This case revealed 2 potential targets that could be used for disease control: androgen receptor positive expression and PD -L1 expression with CPS =20. The use of immune response checkpoint inhibitors (ipilimumab + nivolumab) resulted in partial response followed by stable disease.

Digital Papillary Adenocarcinoma in the Dorsal Proximal Ring Finger

Digital papillary adenocarcinoma (DPA) is a rare but locally aggressive eccrine tumour that has metastatic potential and most frequently found in the upper extremity. It usually presents as an unremarkable swelling of the skin, commonly misdiagnosed as a benign lesion. We present a 67-year-old male who presented with a slowly growing mass of the right middle finger that was biopsied and diagnosed with DPA. The patient was treated with wide local excision (WLE) and sentinel lymph node biopsy by us during the same operative encounter. This report highlights the need for increased clinical vigilance to diagnose DPAs, and that WLE and sentinel lymph node biopsies can be safe and effective treatments offered. Level of Evidence: Level V (Therapeutic).

Digital papillary adenocarcinoma (DPAC) is a rare malignant tumour of the sweat glands, usually in the digits. It has a high rate of recurrence and metastasis, yet there's a lack of guidelines for its diagnosis and management. Therefore, this report aims to evaluate procedures that provide the best outcomes, which will help create a consensus for its management. This case report presents a 47-year old male who had a painless hyperkeratotic patch on his left index finger, with an additional cystic lesion underlying it. This was diagnosed as a hidradenoma, which later changed to DPAC. His finger was amputated through the head of the middle phalanx. A positive sentinel lymph node biopsy led to a left axillary lymph node dissection, which revealed micrometastasis. The patient declined radiotherapy and was on a melanoma follow-up plan. To date there is no evidence of recurrence. Reviewing studies supported the use of immunohistochemical analysis to identify specific markers, especially HPV42. Sentinel lymph node biopsy and radical excision or amputation had the lowest rate of recurrence and thus should be common practice alongside long-term follow-up. Specific follow-up criteria are debated, yet this case may offer a solution by following the melanoma criteria. Histological and immunohistochemical analysis (including HPV42 detection), SLNB, and radical excision or amputation are optimal for DPAC management. Long-term follow-up, possibly using melanoma criteria, is crucial. Further research is needed to establish definitive guidelines.

Characterization of Malignant Adnexal Tumors of the Head and Neck by Targeted Analysis of Cancer Genes and Human Papillomavirus 42

Regional recurrence of digital papillary carcinoma in ipsilateral axillary lymph nodes 12 years after digital amputation – a case report

Malignant Cutaneous Adnexal Tumors and Role of SLNB

Digital papillary adenocarcinoma (DPAca) is an aggressive lesion with high metastatic potential, which is easily misdiagnosed. We present a 55-year-old male with a cystic lesion on his right thumb. Above all else, lesions of the digits should be sent for histopathology routinely, regardless of their history or appearance.

Faculty Opinions recommendation of Clinicopathologic characterization of hidradenoma on acral sites: A diagnostic pitfall with digital papillary adenocarcinoma.

Prognostic classification of skin adnexal carcinomas: Results from a prospective study of 980 patients in the French CARADERM network.

Chronic infection by several "high-risk" human papillomavirus (HPV) types has been causally implicated in several forms of anogenital and oropharyngeal cancers. Now, HPV42, which is usually classified as a "low-risk" type, can be listed as the main cause of digital papillary adenocarcinoma, an uncommon malignant tumor of the fingers and toes. See related article by Leiendecker et al., p. 70 (3).

Rare Cancers Europe: joining forces to tackle a common problem

3015 Background: Rare tumors constitute a heterogeneous group of cancers with limited treatment options and poor outcomes. To address the need for novel therapeutic options in this challenging population, patient-derived xenograft models of rare cancers were developed to screen combinations of anticancer agents. Based on these preclinical data, the NCI Developmental Therapeutics Clinic designed a series of phase 2 clinical trials to assess promising novel combination therapies in patients (pts) with rare tumors. RARE1—the first trial in this series—evaluates the nilotinib-paclitaxel combination, for which a preceding phase 1 study (NCT02379416) recently identified the recommended phase 2 dose (RP2D) and promising clinical activity, including confirmed partial responses (PR) in 3 pts (2 adult granulosa cell ovarian tumors [AGCOT], 1 endometrial cancer) and 1 unconfirmed PR (anal cancer). Given this clinical experience and preclinical activity in rare tumor models, RARE1 (NCT04449549) aims to evaluate the response and mechanism of action of the nilotinib and paclitaxel combination in rare, refractory solid tumors. Methods: Pts with rare tumors meeting the RARECARE definition were treated at the RP2D: nilotinib 300 mg orally twice a day and paclitaxel 80 mg/m 2 IV on days 1, 8, and 15 in 28-day cycles. Response was assessed by RECIST v1.1. Tissue biopsies and research blood were collected at multiple timepoints for pharmacodynamic and genomic analyses. Results: This study enrolled 31 pts of diverse rare cancers as of the data cut-off. Of the 30 evaluable pts, 2 (7%) had confirmed PRs: 1 Ewing sarcoma and 1 ovarian clear cell cancer, completing 12 and 11 cycles (C) on study, respectively. Stable disease (SD) was the best response in 15 pts (50%), of which 5 pts (17%) had prolonged SD: 1 AGCOT (23+ C), 1 testicular embryonal rhabdomyosarcoma (22 C), 1 non-uterine leiomyosarcoma (21 C), 1 salivary gland (12 C), and 1 ampullary adenocarcinoma (6 C). Overall, the median number of cycles completed is 2 (range 0 - 23) and the median progression free survival is 3.8 months. No unexpected treatment-related adverse events have occurred. No grade 3-4 peripheral neuropathy has been observed. Conclusions: Preliminary clinical outcomes for the nilotinib-paclitaxel combination in patients with rare tumors showed encouraging signals of activity. To facilitate further evaluation of response and the underlying mechanism of action for this combination, enrollment now focuses on the 4 tumor types that have previously demonstrated response: Ewing sarcoma, ovarian clear cell carcinoma, AGCOT, and anal cancers. Pharmacodynamic and genomic analyses are also ongoing. This project has been funded in whole or in part with federal funds from the NCI, NIH, under contract HHSN261201500003I. Clinical trial information: NCT04449549 .