Multiple Cutaneous Tumors Research Articles

Clinical, dermoscopic and histopathological features of multiple cutaneous tumours ascribed to sun damage in a Chinese crested dog

AbstractThis case report describes the clinical, dermoscopic and histopathological findings of three different neoplastic lesions (angiokeratoma, squamous cell carcinoma and multiple melanocytomas) and non‐tumoral skin in a hairless Chinese crested dog following chronic sun exposure. The non‐tumoral skin was characterized by “sunburn cells”, collagen degeneration, dermal elastosis and fibrosis, described in most species as caused by UV light exposure. Cutaneous angiokeratomas have been rarely reported in the canine literature. In this particular case we consider a possible correlation with UV damage.

Cutaneous apocrine gland neoplasia in 16 captive African wild dogs (Lycaon pictus)

This retrospective study documents the occurrence of single and multiple cutaneous apocrine gland tumours (CATs) on the dorsal midline of 16 captive African wild dogs (AWDs, Lycaon pictus) derived from 161 submissions to diagnostic laboratories in South Africa, France and Germany between 1997 and 2022. Animals included in the study came from zoological institutions in South Africa (n = 2), France (n = 5) and Germany (n = 1) and ranged from 5 to 14 years of age. Fifteen affected animals were female (94%) and one was male. CATs presented as raised, hairless, multilobular, grey firm masses, consistently located along the dorsal midline. Apart from a single cutaneous apocrine adenoma and a cystadenoma occurring concurrently with two non-cystic adenocarcinomas, neoplasms were consistent with malignant cutaneous apocrine adenocarcinomas with lymphatic spread and visceral metastases. Advanced age and female sex were identified as risk factors. A genetic component or association with the increasing use of GnRH agonist contraceptives was suspected but could not be established. This study highlights the need for close clinical monitoring of AWDs over the age of 5 years for the development of CATs along the dorsal midline and supports early surgical intervention. More research is needed to determine the role of inbreeding, endocrine changes and husbandry factors that may play a role in the development of CATs on the dorsal midline of AWDs.

Electrochemotherapy for multiple cutaneous tumors in immunosuppressed patients

The risk of cutaneous malignancies is significantly higher in immunosuppressed patients compared to the general population. These high-risk skin tumors tend to be aggressive, multiplex, rapidly growing lesions. It is common to see local recurrence after surgical excision. Multiplex tumors are difficult to treat, especially in the head/neck region. Amongst the standard treatment options, electrochemotherapy can be a suitable option. Our aim was to evaluate the efficacy of electrochemotherapy in immunocompromised patients. In 9 immunosuppressed patients, 118 (average: 13, n = 5-27) non-melanoma skin tumors were treated with electrochemotherapy with intravenous administration of bleomycin, according to the ESOPE criteria. The median follow-up was 15 months. 6 months after the treatment, the objective response rate was 96%. We observed complete response in 88%, partial response in 8% and progressive disease in 2% of the treated lesions. In 2%, the response was not evaluable. In immunocompromised patients, electrochemotherapy is an effective and safe therapeutic option for non-melanoma skin tumors. In order to provide more ideal management for this special sub-group, prevention, multidisciplinary approach and optimized immunosuppressive therapy is essential. Orv Hetil. 2023; 164(37): 1462-1468.

Spontaneous multiple cutaneous mixed tumors in Japanese giant salamander Andrias japonicus.

We examined 7 cutaneous mixed tumors in 2 wild-captured Japanese giant salamanders Andrias japonicus. The tumors were either already present and/or increased in size, or newly occurred during capativity. We sampled the 7 tumors from these animals and 3 verrucose protrusions from 3 unaffected animals, as controls, and examined them pathologically and virologically. The tumors (5 mm to 4 cm in size) were papillary protrusions or pendulated on the skin surface. The cut surface of the tumors was white, lobulated, partially hard, and contained mucus. All tumors presented similar histological characteristics of a hyaline structure and exhibited biphasic proliferation, with neoplastic epithelial cells partially composing the pseudo-ductal structure and staining positive for cytokeratin AE1/AE3. Vimentin 3B4-positive blast-like mesenchymal cells proliferated to fill the gaps in the epithelial components. Transition from unique mucous gland to neoplastic tissue was observed. The hyaline structure was stained blue by AZAN stain, Alcian blue-periodic acid-Schiff (PAS) double stain, and toluidine blue (TB) stain of pH 7.0, but was unstained by TB with pH values of 4.1 and 2.5. The mucus in the neoplastic tissue and in the mucous gland in verrucose protrusions was stained blue by Alcian blue-PAS double stain; TB staining at pH 7.0, 4.1, and 2.5 revealed metachromasy. No virus was detected in the tumors. The 7 tumors were diagnosed as cutaneous mixed tumors, and it was confirmed that the neoplastic cells originated from the mucous gland in the dermis. The biological behavior and pathological development of tumors should be elucidated because the tumors have the potential to negatively affect A. japonicus.

28158 Multiple cutaneous neoplasms and uveal melanoma in a patient with Muir-Torre syndrome

Introduction: Lynch syndrome is caused by germline mutations in mismatch repair genes and increases the risk of gastrointestinal and urogenital tract malignancies. The Muir-Torre subtype is additionally associated with keratoacanthomas and sebaceous carcinomas. We present a patient with Lynch syndrome with colon cancer who later developed metastatic uveal melanoma, multiple basal cell carcinomas (BCCs), and sebaceous carcinoma.

Common Cutaneous Neoplasms in Patients with Immunodeficiency: A Case Series

Abstract Through humoral and cell-mediated mechanisms, the immune system plays a vital role in protecting every organ system. Disorders of the immune system may result in various cutaneous manifestations, including cutaneous malignancies. In patients with immunodeficiency, the risk of development of malignant cutaneous neoplasms is substantially increased. This increased risk may be due to oncogenic viruses that find a suitable microenvironment for tumorigenesis and cancer development. A subset of cutaneous malignancies that develop in patients with immunodeficiency may show aggressive clinical and biological behavior. Here, we report six cases of highly aggressive and deadly cutaneous neoplasms that arose in patients with a known history of immunodeficiency: two cases of Kaposi sarcoma in patients with immunosuppression due to human immunodeficiency virus infection; a case of Merkel cell carcinoma and a case of squamous cell carcinoma (SCC) in patients receiving immunosuppressive drugs after organ transplant; a case of multiple cutaneous tumors, including invasive melanoma, SCC, and sebaceous carcinoma, in a patient with hypogammaglobulinemia and a history of organ transplant; and a case of basal cell carcinoma and melanoma in situ in a patient with primary immunodeficiency.

BRCA1-associated protein (BAP1)-inactivated melanocytic tumors.

Although discussed using variable terminology, cutaneous BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma-like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT.

Abstract 1722: Spectrum of solid malignancies associated with mutations in CYLD gene

Abstract Introduction: The CYLD gene product is a de-ubiqutinating enzyme involved in regulation of NF-kappaB signaling. Inactivating germline mutations in CYLD are the cause of Brooke-Spiegler syndrome characterized by multiple cutaneous tumors (cylindromas, trichoepitheliomas and spiradenomas) and tumors of salivary glands. Little is known about the role of CYLD in the development of solid organ malignancies. Methods: We retrospectively analyzed CYLD gene mutations detected in a large database of solid tumors genetically profiled (NGS of 592 genes) at a reference laboratory (Caris Life Science, Phoenix, AZ). Results: CYLD pathogenic mutations were identified in 235 tumor samples (0.4% of the tumors analyzed). The most common primary sites included lung (60), endometrium (15) and anus (10). Histologically, the majority of the tumors were classified as squamous (71) and adenocarcinoma (59). A number of mutations were identified, most commonly affecting codons p.N722fs (27), p.S371* (16) and p.P771S/p.P771L (12). 38 cases had only CYLD mutations detected, while the majority of associated mutations occurred in TP53 (45%). Numerous co-occurring pathogenic mutations were present in oncogenes (e.g. PIK3CA in 41, KRAS in 33, BRAF 17) and/or tumor suppressor genes (e.g. APC in 40, PTEN in 36, BRCA2 in 25, RB1 in 23). Conclusion: Our study provides the largest database analysis of CYLD gene mutations in solid tumors and shows the distribution in numerous primary tumor sites previously unrecognized in association with CYLD. Additional studies may reveal unexpected germ-line associations and will be pursued in the future. Citation Format: Michelle Ellis, Jeff Swensen, Zoran Gatalica. Spectrum of solid malignancies associated with mutations in CYLD gene [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1722.

Multiple Cutaneous Tumors including Merkel Cell Carcinoma in a Cat

Multiple Cutaneous Tumors including Merkel Cell Carcinoma in a Cat

Diagnosis of Xeroderma pigmentosum variant in a young patient with two novel mutations in the POLH gene.

We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a young Caucasian patient with phototype I, who exhibited a high sensitivity to sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations in the POLH gene, which encodes the translesion DNA polymerase η, with loss of function due to two independent exon skippings, are reported to be associated as a compound heterozygous state in the patient. Western blot analysis performed on proteins from dermal fibroblasts derived from the patient and analysis of the mutation spectrum on immunoglobulin genes produced during the somatic hypermutation process in his memory B cells, show the total absence of translesion polymerase η activity in the patient. The total lack of Polη activity, necessary to bypass in an error-free manner UVR-induced pyrimidine dimers following sun exposure, explains the early unusual clinical appearance of this patient.

A case of Carney complex misdiagnosed as neurofibromatosis type 1 – Diagnostic difficulty in a rare disease

We experienced a diagnostically challenging case of Carney complex (CNC). A 24-year-old woman had a past history of surgical removal of multiple cutaneous tumors in the childhood. She was followed as a patient of neurofibromatosis type 1 (NF1) and referred to our hospital for further treatment after she grew up to adulthood. At our hospital, several cutaneous tumors were excised, and the pathological diagnosis was myxoma arising from not deep soft tissue but cutis (so-called cutaneous myxoma). Despite previous clinical diagnosis of NF1, because of the probability of CNC, detailed systemic examination was undertaken including radiological and endocrinological tests. Imaging techniques showed multiple lumps in both breasts, a mass in left atrium and nodular lesions in adrenal glands. Serum ACTH level was markedly suppressed. Surgically resected specimens revealed breast myxomas, cardiac myxoma and primary pigmented nodular adrenocortical disease (PPNAD). These findings met the diagnostic criteria for CNC. Genetic analysis revealed known non-sense mutation of PRKAR1A c.124C>T (p.R42X) (ClinVar ID 41382). Her 50-year-old mother was also shown to have cardiac myxomas, radiological finding of breast myxomatosis and the same PRKAR1A mutation as her daughter. In the present case, the accurate diagnosis of CNC was difficult not only because CNC is a rare disease but also because skin pigmentation was not obvious. Since cardiac myxoma might result in poor or fatal outcome, early and accurate diagnosis of CNC and subsequent systemic investigation including heart are important. Although pediatric cutaneous myxomas are rare, multiple cutaneous myxomas might suggest the possibility of CNC. In such cases, systemic investigation should be done for the accurate diagnosis.

Canine Cutaneous Plasmacytosis: 21 Cases (2005-2015).

BackgroundCutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous plasma cell tumors, in the absence of multiple myeloma. Although rare in both humans and dogs, treatment recommendations are usually extrapolated from multiple myeloma protocols. To date, no case series of CP have been described in the veterinary literature.Hypothesis/ObjectivesTo describe clinical presentation, determine treatment response rates and duration, and report overall survival of dogs with CP.AnimalsTwenty‐one client‐owned dogs with CP.MethodsMedical records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs with ≥3 lesions. Dogs with suspicion of multiple myeloma were excluded.ResultsThe most commonly affected breeds were the golden (5/21) and Labrador retriever (3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions commonly were described as round, raised, pink‐to‐red, and variably alopecic or ulcerated. The most commonly used drug protocol was combined melphalan and prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single‐agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all treatments combined, the median progression‐free interval after the first treatment was 153 days. The median survival time from the first treatment was 542 days.Conclusions and Clinical ImportanceAlkylating agents were effective in inducing remission of CP; corticosteroids, melphalan, and lomustine were the most commonly used drugs. Survival times were similar to those reported in dogs with multiple myeloma treated with alkylating agents.

Examining the Role of Transmission of Chelonid Alphaherpesvirus 5.

Marine turtle fibropapillomatosis (FP) is a devastating neoplastic disease characterized by single or multiple cutaneous and visceral fibrovascular tumors. Chelonid alphaherpesvirus 5 (ChHV5) has been identified as the most likely etiologic agent. From 2010 to 2013, the presence of ChHV5 DNA was determined in apparently normal skin, tumors and swab samples (ocular, nasal and cloacal) collected from 114 olive ridley (Lepidochelys olivacea) and 101 green (Chelonia mydas) turtles, with and without FP tumors, on the Pacific coasts of Costa Rica and Nicaragua. For nesting olive ridley turtles from Costa Rica without FP, 13.5% were found to be positive for ChHV5 DNA in at least one sample, while in Nicaragua, all olive ridley turtles had FP tumors, and 77.5% tested positive for ChHV5 DNA. For green turtles without FP, 19.8% were found to be positive for ChHV5 DNA in at least one of the samples. In turtles without FP tumors, ChHV5 DNA was detected more readily in skin biopsies than swabs. Juvenile green turtles caught at the foraging site had a higher prevalence of ChHV5 DNA than adults. The presence of ChHV5 DNA in swabs suggests a possible route of viral transmission through viral secretion and excretion via corporal fluids.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Is Highly BCL-2 Dependent and Sensitive to Venetoclax

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a particularly aggressive hematologic malignancy with median survival of 80% bone marrow blasts. His BPDCN carried the mutations ASXL1 Y581fs*, ASXL1 E553fs*, GNB1 K57E, IDH2 R140W, and NRAS G12D, and expressed high levels of BCL-2 protein in bone marrow and skin. BH3 profiling of a skin tumor biopsy revealed marked BCL-2 dependence and dynamic BH3 response to venetoclax (4 hr delta priming 55.6%). We treated him using a regimen recently FDA-approved for chronic lymphocytic leukemia (CLL) consisting of weekly dose escalation (20 -> 50 -> 100 -> 200 mg), to a target dose of 400 mg daily. At the time of this writing, he had reached 200 mg without significant toxicity, including no evidence of tumor lysis syndrome. His skin disease has responded remarkably (Figure), with the first response evident within 10 days. Our data suggests that BPDCN is highly sensitive to BCL-2 inhibition, which could provide an urgently needed new treatment for patients with this disease. We propose that BCL-2 inhibition should undergo expedited clinical evaluation in BPDCN. In addition, this case offers an example of precision cancer medicine by functional rather than genetic means. Disclosures Davids:Infinity: Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Gilead: Honoraria; Janssen: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Stone:ONO: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Roche: Consultancy; Celator: Consultancy; Abbvie: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Agios: Consultancy; Celgene: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Karyopharm: Consultancy; Jansen: Consultancy; Pfizer: Consultancy; Juno Therapeutics: Consultancy; Merck: Consultancy; Sunesis Pharmaceuticals: Consultancy; Xenetic Biosciences: Consultancy. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Letai:AbbVie: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Research Funding; Tetralogic: Consultancy, Research Funding. Lane:N-of-1: Consultancy; Stemline Therapeutics: Research Funding.

Long-lasting multiple cutaneous tumors

Long-lasting multiple cutaneous tumors

Tumores del corazón

Una revisión de la literatura sobre los tumores cardíacos. Un estudio anatomo-patológico de demasiados casos de neoplasia corazón. En el caso N ° 1, sin observaciones clínicas, el autor encontró múltiples tumores cutáneos, un tumor en el cerebelo, y en la base del corazón, una masa tumoral voluminosa. entrar en el epicardio y que rodea la aorta y la arteria pulmonar. 800 C.C. de un exudado de sangre, fueron encontrados en el pericardio. Basando sus deducciones en el estudio de la histología, el autor asume las diferentes localizaciones tumorales, al ser una transformación-neuro sarcomatose de tumores que inicialmente fueron meramente de naturaleza neuro-fibromatose. Caso N ° 2 se refiere a un tubo de adeno-carcinoma de riñón, con metástasis múltiples en la piel, los pulmones, el hígado, el peritoneo y el corazón. En el último órgano llamado, los nódulos metastásicos, se produjeron en los tabiques interauricular e interventricular, así como en las paredes de ambos ventrículos. No hay síntomas de algún problema cardiovascular se indican en la historia clínica de este caso.

Global Contributions to the Understanding of DNA Repair and Skin Cancer

Living organisms exposed to sunlight have developed mechanisms to repair the damage that UVR induces in their DNA. These DNA repair systems are present in most life forms including bacteria, yeast, rodents, and mammals. Three rare human genetic diseases have defects in the DNA repair system called nucleotide excision repair (NER). Patients with xeroderma pigmentosum (XP) have defective NER and a more than 10,000-fold increased frequency of skin cancer, whereas patients with Cockayne syndrome (CS) or with trichothiodystrophy (TTD) have NER defects without increase in cancer. These are strikingly different clinical phenotypes (Figure 1). The dramatic differences in their manifestations reflect the complexity of DNA repair and the broad scope and central role of DNA repair on preservation of diverse biological functions. This article will review the major milestones in our understanding of DNA repair and skin cancer (Table 1). These include recognition of the clinical diseases, understanding the types of damage sunlight causes in the DNA, recognition of DNA repair in different organisms, discovery of defective DNA repair in humans, cloning of multiple human DNA repair genes, and identification of UV-type mutations in skin cancer.

Multiple secondary cutaneous tumours following electron beam radiotherapy for cutaneous malignancies of the scalp

Electron beam radiation is a commonly used and effective treatment modality for cutaneous malignancies. Secondary cutaneous malignancies arising in electron beam treatment sites are rarely reported. We report on seven patients who developed multiple secondary tumours arising within and immediately around electron beam radiation treatment sites in the setting of treatment for diffuse primary disease or as adjunctive therapy for aggressive cutaneous malignancies.

Sığır Deri Papillomatozisinin Histopatolojik, İmmunohistokimyasal ve Moleküler Araştırılması

Summary In animals and man, some forms of cutaneous papillomas are caused by papillomaviruses. Twelve different genotypes of bovine papillomavirus (BPV) have been identified. BPV-1 through BPV-12 are all strictly species-specific. BPV-1 and BPV-2 are associated with fibropapillomas in cattle; these tumors are formed by excessive proliferation of virus-infected dermal fibroblasts and epidermal keratinocytes. In the present study well known diagnostic procedures including histopathological, immunohistochemical and molecular methods were used for the diagnosis of bovine papillomavirus infection.Samples were taken randomly from five cattle with multiple cutaneous tumor formations for the diagnosis of bovine papillomavirus infection occurring commonly in herds.In the present study five cattle were examined for the presence of multiple cutaneous tumors. Cutaneous fibropapillomatosis were confirmed histopathologically and immunohistochemically. BPV-1 and BPV-2 which are etiological agents for the bovine cutaneous fibropapillomatosis were investigated by PCR. BPV serotyping was performed from five cattle all coming from three different farms. In conclusion papillomaviral DNA was detected by the PCR. The amplified long control region (LCR) DNA sequence was identical to that of BPV-1 and negative for the BPV-2 DNA. When considered economical impact of the disease associated with the abundance of the infection significance of protective measures and vaccine studies come forward.

Recurrent CYLD Nonsense Mutation Associated With a Severe, Disfiguring Phenotype in an African American Family With Multiple Familial Trichoepithelioma

To the Editor:Recently, Kazakov et al1 performed a clinicopathologic and genotypic analysis on a series of 16 patients suffering from multiple (familial) trichoepitheliomas (MFT: MIM 601606) and found mutations in the CYLD gene in 46%. Based on the frequent presence of CYLD mutations in MFT, it, alo