Does systemic hydrochlorothiazide increase the risk of developing ultraviolet radiation-induced skin tumours in hairless mice?

Hydrochlorothiazide (HCTZ) is a frequently prescribed diuretic that exhibits photosensitizing properties. It is used to treat hypertension and edema. Dermato-epidemiological studies in various populations have linked HCTZ treatment with increased risk of particular types of skin cancer, including malignant melanoma (lentigo subtype), and both basal cell carcinoma and squamous cell carcinoma (SCC). This study investigated whether either of two different doses of HCTZ increased the risk of SCC development in mice exposed to ultraviolet radiation (UVR). A total of three groups of hairless mice were used in this study (total, N = 71). One group received a low dose (0.26 mg/mouse/day) and another group received a high dose (0.52 mg/mouse/day) of HCTZ in their drinking water; a third UVR control group received only tap water. All three groups were irradiated with UVR until the mice developed three tumours that were 4 mm in size. The times to SCC tumour development were recorded. In the low-dose group, the median time to develop an SCC tumour was 170 days; in both the high-dose group and the control group, the median time to develop anexd SCC tumour was 163 days (p ≥ 0.331). In our hairless mouse model, we found that mice treated with UVR plus HCTZ did not develop SCCs more rapidly than mice treated with UVR but not HCTZ.

Dermatofibrosarcoma Protuberans in Children.

OPINION STATEMENT: Paediatric dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue malignant tumour which displays aggressive local behaviour and has low metastatic potential. The diagnosis is often delayed as DFSP is usually mistaken for other skin conditions, particularly in the early stages of disease. DFSP tends to follow an indolent course after the initial presentation with what is often described as a "rubbery lump". As the disease progresses, the lump tends to enlarge, change colour, and exhibit a more nodular consistency. In rare cases, DFSP can present as an ulcerated exophytic lesion or a depressed area of skin, making diagnosis even more challenging. A high index of suspicion is warranted for early diagnosis, and referral to a specialist unit with expertise in both oncologic resection and reconstruction. DFSP tumours arise from the dermis and grow with finger-like projections. Therefore, in cosmetically sensitive or functionally important locations, an excision and analysis technique that assesses all excision margins is the gold standard of care. Slow Mohs technique performed with en bloc excision is a well-tolerated option for oncologic resection of the tumour. Mohs technique can also be considered but can be challenging in children for reasons explained below. As an alternative, depending on the anatomical location, tumours can be excised with a wide local excision. While an excision technique that incorporates the deep fascia with a 3-cm peripheral margin is acceptable in adults, planning of the excision margin in children should involve consideration of preoperative imaging with MRI, site of the tumour, age, and physical built of the child. Patients should be offered all treatment options considering the local outcomes, available expertise, and cost. A multidisciplinary approach and good communication between team members is crucial. Close collaboration with a pathologist who is familiar with sectioning technique that allows margin control is of paramount importance. Soft tissue reconstruction should be performed immediately after oncologic clearance, although a staged approach may be required. Adjuvant radiotherapy should be avoided in children due to the long-term risk of secondary malignancies and potential for growth disruption.

Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

Dermoscopy of Malignant Skin Tumours: What's New?

Dermoscopy represents a new and effective tool that assists dermatologists in improving the accuracy of clinical diagnosis in onco-dermatology. The aim of this article is to provide an overview of the latest and important dermoscopic progress and observations in this ever-evolving field of dermatology.

Structural and functional 3D mapping of skin tumours with non-invasive multispectral optoacoustic tomography.

BACKGROUND: Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature. METHODS: Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared. RESULTS: We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation. CONCLUSION: Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

Assessment of SIAscopy in the triage of suspicious skin tumours.

BACKGROUND/PURPOSE: Spectrophotometric Intracutaneous Analysis (SIAscopy) is a non-invasive, computerized technique for the diagnosis of pigmented skin tumours. The analysis is based on the evaluation of skin chromophores, i.e. melanin, haemoglobin and collagen within the epidermis and papillary dermis. Our aim was to assess the diagnostic validity of SIAscopy in the detection of melanoma and non-melanoma skin cancers compared to the clinical-dermoscopic diagnosis and the histopathologic results of the excised lesions. METHODS: In total, 188 lesions of 180 patients were examined by dermoscopy and SIAscopy. A SIAscopy scoring system was first compared with the clinical-dermoscopic diagnosis and then with the histopathologic diagnosis of the excised lesions. RESULTS: With respect to the clinical-dermoscopic evaluation, SIAscopy had sensitivity and specificity values of 85.7% and 65.4% respectively. Of the 188 evaluated lesions, 44 were excised with histopathologic examination revealing 31 malignant tumours, including 18 melanomas. With respect to histopathology SIAscopy had a sensitivity of 83.9%. Seven of the 13 benign excised lesions were scored as malignant by SIAscopy resulting in a specificity of 46.1%. CONCLUSION: SIAscopy cannot replace the standard of care in skin cancer diagnosis, which includes clinical and dermoscopic examination. However, considering that the technique does not require specific training and expertise, it might represent an additional, relatively cost-effective tool to select lesions for referral.

The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours.

BACKGROUND: The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports. PATIENTS AND METHODS: From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up. RESULTS: The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US "positive" patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US "negatives", 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies. CONCLUSIONS: US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed.

Histopathological and Ultrastructural Study of a Canine Langerhans Cell Tumour (Canine Cutaneous Histiocytoma).

Canine cutaneous histiocytoma (CCH) represents a significant proportion of dog skin tumours, often manifesting as the most common neoplastic skin condition in young animals. Predominantly affecting dogs under four, these tumours appear primarily as solitary lesions that may regress spontaneously. This study, conducted over five years at the University of Trás-os-Montes e Alto Douro, involved a detailed histopathological and ultrastructural examination of 93 CCH cases. Histologically, these tumours showed distinct patterns of lymphoid infiltration, which contributed to their classification into four groups based on the inflammatory response and histological architecture. Most tumours displayed signs of epidermal invasion and frequent mitotic figures, with necrosis present in over half of the cases. Ultrastructurally, the neoplastic cells were characterised by pleomorphism, abundant organelles, and adherens-type junctions. This study offers significant insights into the pathophysiology and morphological characteristics of CCH, underscoring the importance of detailed histological and ultrastructural analysis in accurately diagnosing and understanding this common canine tumour.

CYLD in health and disease.

CYLD lysine 63 deubiquitinase (CYLD) is a ubiquitin hydrolase with important roles in immunity and cancer. Complete CYLD ablation, truncation and expression of alternate isoforms, including short CYLD, drive distinct phenotypes and offer insights into CYLD function in inflammation, cell death, cell cycle progression and cell transformation. Research in diverse model systems has shown that these are mediated via CYLD regulation of cellular pathways including the NF-κB, Wnt and TGF-ß pathways. Recent biochemical advances and models have offered new insights into the regulation and function of CYLD. In addition, recent discoveries of gain-of-function germline pathogenic CYLD variants in patients with a neurodegenerative phenotype contrast with the more widely known loss-of-function mutations seen in patients with CYLD cutaneous syndrome and with sporadic cancers. Here, we provide a current review of mechanistic insights into CYLD function gained from CYLD animal models, as well as an update on the role of CYLD in human disease.

Incidence and the risk of occurrence of benign and malignant canine skin tumours in Poland - a five-year retrospective study.

Introduction: The aim of the study was to compile data on the frequency and distribution of canine skin tumours and determine the risk of these being malignant as opposed to benign. This determination proceeded from tumour histogenesis and gave consideration to the dog's breed, sex, age and the anatomical location of tumours. Material and Methods: This retrospective five-year epidemiological study included 3,139 canine skin tumours collected in Poland. A univariable logistic regression analysis was performed to determine the odds ratios (ORs) with 95% confidence intervals (CIs). Results: Microscopic analysis showed a significant predominance of benign tumours (65.02%) as well as mesenchymal and melanocytic tumours (59.57%). The most frequently diagnosed were mast cell tumours, accounting for 13.79% of all skin tumours, and other common tumour types were lipomas (6.40%), haemangiopericytomas (5.96%) and malignant melanomas (4.65%). The risk of malignant versus benign tumours was 1.212 times higher in the female than in the male dogs. A higher risk of development of malignant epithelial tumours was found in boxers (OR 4.091), German shepherds (OR 4.085) and flat-coated retrievers (OR 43.596). A higher risk of development of malignant mesenchymal tumours was found in golden retrievers (OR 4.693), boxers (OR 2.342), bulldogs (OR 3.469) and Maltese (OR 2.757). Conclusion: The results may serve as a reference point for further studies of the complex biology of canine skin tumours.

Cutaneous Mixed Tumour: A Rare Presentation of a Scrotal Lump Mimicking an Accessory Testis.

Cutaneous mixed tumour (CMT), also known as chondroid syringoma (CS), is a rare benign tumour composed of epithelial, myoepithelial, and mesenchymal components with an incidence of less than 0.01% of primary skin tumours. It is more common in males and typically presents as a painless slow-growing firm mass in the subcutis of the head and neck region. Genital regions are very rarely involved. We present the case of a 50-year-old male with a 10-year history of an asymptomatic gradually enlarging mass in the upper scrotum. A surgical excision was performed. Microscopic examination showed features of CMT. This case highlights the diagnostic challenges associated with scrotal CMT and surgical management of these lesions. Additionally, we endorse the recommended terminology of CMT used by the fifth edition of WHO Classification of Skin Tumours (2023).

[Reconstruction of orbital exenteration defects: about 20 cases]. / Couverture des cavités d´exentération: à propos de 20 cas.

The face is social support. Eyes allow the individual to interact with the environment and others. Orbital exenteration defects are the results of extreme disfiguring surgery, leading to functional, aesthetic and psychological sequelae. Reconstruction is essential and must meet several objectives: filling the cavity and closing any communications with the adjacent structures, obtaining rapid healing, allowing for local monitoring and finally enabling patients to reintegrate into society and achieve a satisfactory quality of life. We here present our experience in filling and reconstructing these cavities. Our study involved 20 patients with orbital exenteration defects over a period of 5 years (February 2015-February 2020). We analyzed the epidemiological features, clinical profile, and methods of the reconstruction as well as patients´ outcomes in our hospital. The average age of patients was 58.5 years. Squamous cell carcinoma was the main histological type, followed by basal cell carcinoma. Filling techniques included directed wound healing (7 cases), temporalis fascia flap (2 cases), temporalis muscle flap (10 cases). Methods of reconstruction included directed wound healing (6 cases), full-thickness skin graft (1 case), mediofrontal flap (6 cases; alone or associated with the temporalis muscle), converse scalping flap in three cases. Free latissimus dorsi flap was used in two cases. Thirteen patients showed good outcomes, with good healing after an average follow-up period of 9 months. The most common complication was infection and suture release. Two patients were lost to follow-up. Orbital exenteration defects can be approached in many ways. Temporalis muscle flap has been shown to be a robust and safe choice as well as an excellent filling solution. Prostheses are an aesthetic but expensive solution that should be developed in our hospital.

Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer.

A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five-83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.

Congenital Myofibroblastic Skin Tumours in a Newborn Piglet Resembling the Multicentric Form of Infantile Myofibromatosis.

A 2-day-old female piglet was submitted with multiple congenital, nodular skin masses located on the head, neck, trunk and legs. Histopathological examination revealed the presence of nodular, cutaneous tumours with a biphasic growth pattern and comprising a population of undifferentiated, oval or slightly polygonal, frequently perivascularly located cells and a population of spindle-shaped, fibroblast-like cells arranged in bundles. Multifocally, tumour cells infiltrated subcutaneous adipose and muscular tissue. Immunohistochemically, the undifferentiated tumour cells expressed vimentin and calponin, whereas the spindle-shaped tumour cells were positive for vimentin, α-smooth muscle actin and calponin. Based on these findings, the diagnosis was myofibroblastic tumours closely resembling the multicentric form of human infantile myofibromatosis.

Giant Mushroom-like Neglected Basal Cell Carcinoma of the Shoulder with Spontaneous Bleeding: A Successful Surgical Approach.

INTRODUCTION: Giant basal cell carcinomas (GBCCs) are extremely rare and typically more aggressive than their predecessor subtype. GBCCs with mushroom-like morphology have rarely been reported, with only one other case identified in the literature. Here we present a unique case of a neglected giant mushroom-like BCC that was treated successfully. CASE DESCRIPTION: An 81-year-old male patient presented with a large ulcerative mass on his back. He had a medical history of chronic heart failure and atrial fibrillation, which were controlled with heart medication. During a routine visit to change the dressing of the lesion, the central pedunculated stalk underwent spontaneous haemorrhaging which led to massive blood loss. The patient was treated for shock and the lesion was completely excised under emergency surgery. The tumour was sent for histopathological assessment after complete surgical removal. Recovery was successful with good postoperative results and no recurrence was reported in the 12 months following discharge. DISCUSSION: The patient was under long-standing anticoagulant therapy that contributed to the untimely rupture of the pedunculated lesion and led to spontaneous heavy haemorrhaging. Treatment for such giant lesions can be complex, especially in patients with co-morbid conditions. Careful assessment and early treatment are paramount for successful results. CONCLUSION: Complete removal of such lesions is very successful for treating GBCCs. LEARNING POINTS: Giant mushroom-like basal cell carcinoma is a rare phenomenon that may only occur as a result of patient neglect and failure to seek early medical intervention.Patients with such lesions require special attention as multiple co-morbidities can play a role in disease progression.Early aggressive surgical intervention may be the best strategy for successful treatment and to prevent recurrence.

Multifocal cutaneous non-epitheliotropic B-cell lymphoma in a cat.

CASE SUMMARY: Skin tumours are the second-most common form of feline cancer after haematopoietic neoplasms and are often malignant. Cutaneous lymphoma is uncommon in cats and can be classified as epitheliotropic (typically of T-cell origin) or non-epitheliotropic (either of T-cell or B-cell origin). The present study describes a case of multifocal cutaneous non-epitheliotropic B-cell lymphoma. The skin nodules were multiple and variable in size; showed rapid progression; were alopecic and erythematous in appearance and pruritic and ulcerated; and were mostly located on the trunk. Nodule biopsies revealed the presence of uniform medium-to-large round neoplastic cells that infiltrated the dermis and subcutis. The neoplasias were consistent with a round cell cutaneous tumour and did not show evidence of epitheliotropism. Furthermore, immunohistochemical assessments indicated an immunophenotype characterised by round cells with a strong membrane and cytoplasmic positivity for the CD20 antigen, consistent with a lymphocyte of B-cell origin. RELEVANCE AND NOVEL INFORMATION: Cutaneous non-epitheliotropic B-cell lymphoma in cats is rare and was previously reported to appear as single dermal and subcutaneous masses that are variable in size and generally develop in the tarsal region. To our knowledge, this is the first report to describe multifocal cutaneous non-epitheliotropic B-cell lymphoma in a cat.

A Painful Step - Pendulating Plantar Eccrine Poroma.

BACKGROUND: Eccrine poroma is a benign tumour of eccrine duct epithelium. The usual clinical presentation is nodular. CASE REPORT: We present a 78-year-old man with a painful pendulating flesh-coloured malodorous plantar tumour. Differential diagnoses included telangiectatic granuloma, acrochordon, basal cell or squamous cell carcinoma, cylindroma, amelanotic melanoma, and verruca. Microbiological investigations identified numerous bacteria including Corynebacterium striatum, Streptococcus dysgalactiae, Staphylococcus aureus, Citrobacter koseri. We performed surgery since the tumour hampered his mobility. Histopathology revealed a well-circumscribed tumour composed of cuboidal cells with eosinophilic cytoplasm. Healing was unremarkable. CONCLUSIONS: Pendulating plantar eccrine poroma is a rare clinical presentation of this benign adnexal tumour. Often asymptomatic, in some cases the tumour may become painful. Because of the bacterial colonisation, it could lead to deep soft tissue infections. Malignant transformation is possible. Surgical removal is the treatment of choice.

Recurrent dermatofibrosarcoma protuberans: challenging a surgeon's dexterity for the 'tricky' margins.

Soft tissue tumours represent 0.2%-1% of all breast malignancies. [Al Tarakji M, Toro A, and Di Carlo I, et al (2015) Unusual presentation of dermatofibrosarcoma protuberans in a male patient's breast: a case report and review of the literatureWorld J Surg Oncol13 158 https://doi.org/10.1186/s12957-015-0562-1]. Out of those, Dermatofibrosarcoma protuberans (DFSP) of the breast is extremely rare, especially in men with only six cases, including this case, reported so far. We report a case of recurrent DFSP in a 35-year-old male after a latency of 8 years in the region of previous surgical scar. It was managed by a wide local excision followed by reconstruction using latissimus dorsi flap. It is important to carefully manage recurrent cases because the post-operative margin status is an important determinant of recurrence, and therefore, requires vigilant resection of the tumour without causing extensive morbidity to the patient.

Human polyomavirus DNA detection in keratoacanthoma and Spitz naevus: no evidence for a causal role.

Keratoacanthomas (KA) and Spitz naevus (SN) are both lesions with unknown aetiology; therefore, the possibility of a viral involvement, more specifically the involvement of human polyomaviruses (HPyV), was investigated. In total, 22 cases of KA and 25 cases of SN were tested for the presence of HPyVs. DNA was extracted and amplified by multiplex PCR and thereafter tested with a multiplex bead-based assay for HPyVs (BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, TSPyV, HPyV6, 7 and 9) and two primate viruses (SV40 and LPyV). HPyV DNA was found in 20 of the 47 lesions. There was no significant difference in HPyV DNA detection frequency between patients diagnosed with KA and patients diagnosed with SN, nor any over-representation of a specific HPyV type in any of the two patient categories. In conclusion, evidence for a specific aetiological role of any of the above tested HPyVs in either KA or SN was not disclosed.

PIK3CA and AKT1 mutations in hidradenoma papilliferum.

AIMS: Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on PIK3CA and AKT1 mutations, which are both reported to be detected in 33% of mammary intraductal papillomas. METHODS: In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and ß-catenin were performed. Furthermore, PIK3CA, AKT1, BRAF and KRAS hot spot mutations were examined by Sanger sequencing. RESULTS: Morphologically, all HPs had a papillary and tubular architecture with a biphasic pattern of epithelial and myoepithelial cells. Immunohistochemistry revealed that oestrogen receptor expression was restricted to epithelial cells, whereas p63 and SMA were exclusively expressed in myoepithelial cells. The patterns of p53 and ß-catenin immunostaining suggested wild-type genotypes. Direct sequencing revealed the presence of somatic PIK3CA mutations (Ex9. c.1633G>A, p.E545K and Ex20. c.3140A>G, p.H1047R) in two of the HPs and an AKT1 (c.49G>A, p.E17K) mutation in one. BRAF and KRAS mutations were not found in any of the HP cases. CONCLUSIONS: PIK3CA and AKT1 are frequently mutated in HP tumours (29% and 14%, respectively). PIK3CA/AKT1 pathway alterations in HP further support the hypothesis that HP is the vulvar (anogenital mammary-like gland) analogue of breast intraductal papilloma.