Dermal Tumor Research Articles

Integrated bioinformatics analysis of core regulatory elements involved in keloid formation

BackgroundKeloid is a benign fibro-proliferative dermal tumor formed by an abnormal scarring response to injury and characterized by excessive collagen accumulation and invasive growth. The mechanism of keloid formation has not been fully elucidated, especially during abnormal scarring. Here, we investigated the regulatory genes, micro-RNAs (miRNAs) and transcription factors (TFs) that influence keloid development by comparing keloid and normal scar as well as keloid and normal skin.MethodsGene expression profiles (GSE7890, GSE92566, GSE44270 and GSE3189) of 5 normal scar samples, 10 normal skin samples and 18 keloid samples from the Gene Expression Omnibus (GEO) database were interrogated. Differentially expressed genes (DEGs) were identified between keloid and normal skin samples as well as keloid and normal scar samples with R Project for Statistical Computing. Gene Ontology (GO) functional enrichment analysis was also performed with R software. DEG-associated protein–protein interaction (PPI) network was constructed by STRING, followed by module selection from the PPI network based on the MCODE analysis. Regulatory relationships between TF/miRNA and target genes were predicted with miRnet and cytoscape. Core regulatory genes were verified by RT-qPCR.ResultsWe identified 628 DEGs, of which 626 were up-regulated and 2 were down-regulated. Seven core genes [neuropeptide Y(NPY), 5-hydroxytryptamine receptor 1A(HTR1A), somatostatin (SST), adenylate cyclase 8 (ADCY8), neuromedin U receptor 1 (NMUR1), G protein subunit gamma 3 (GNG3), and G protein subunit gamma 13 (GNG13)] all belong to MCODE1 and were enriched in the “G protein coupled receptor signaling pathway” of the GO biological process category. Furthermore, nine core miRNAs (hsa-mir-124, hsa-let-7, hsa-mir-155, hsa-mir-26a, hsa-mir-941, hsa-mir-10b, hsa-mir-20, hsa-mir-31 and hsa-mir-372), and two core TFs (SP1 and TERT) were identified to play important roles in keloid formation. In the TF/miRNA-target gene network, both hsa-mir-372 and hsa-mir-20 had a regulatory effect on GNG13, ADCY8 was predicted to be target by hsa-mir-10b, and HTR1A and NPY were potentially by SP1. Furthermore, the expression of core regulatory genes (GNG13, ADCY8, HTR1A and NPY) was validated in clinical samples.ConclusionsGNG13, ADCY8, NPY and HTR1A may act as core genes in keloid formation and these core genes establish relationship with SP1 and miRNA (hsa-mir-372, hsa-mir-20, hsa-mir-10b), which may influence multiple signaling pathways in the pathogenesis of keloid.

A Large Mass over the Foot due to the Coexistence of an Eccrine Poroma and a Poroid Hidradenoma: A Case Report.

Eccrine poroma and poroid hidradenoma are uncommon benign poroid neoplasms derived from eccrine sweat glands. There are four types of poroid neoplasms according to the position within the skin layer: hidroacanthoma simplex, eccrine poroma, dermal duct tumor, and poroid hidradenoma. Poroid neoplasms usually arise as slow-growing solitary lesions and can present different clinical presentations, such as a foot mass, an ulceration lesion, a solid cyst, a bleeding lesion or suspected melanoma. Extremities are the most common sites, especially hands and feet. However, the coexistence of these two tumors in a single lesion is extremely rare. Surgical excision represents the main treatment and can be curative, preventing malignant changes and recurrence. We describe a rare solitary tumor over the foot with clinical and histopathological features of an association of an eccrine poroma and a poroid hidradenoma that was surgically treated with no recurrence at the midterm follow-up. Level of Evidence IV, Case Report.

26232 Cutaneous metastatic breast cancer in zosteriform distribution

An 82-year-old Caucasian female presented with violaceous papules and nodules in a zosteriform distribution across her abdomen. A punch biopsy was performed which demonstrated a dermal neoplasm with nests of poorly differentiated pleomorphic cells with focal areas of ductal differentiation. These findings are consistent with metastatic breast carcinoma in a zosteriform distribution. Cutaneous metastasis from primary breast cancer is typically nodular, with lesions being single or multiple. Cutaneous metastasis represents late disease findings, and is indicative of advanced disease progression.

28154 Endocrine mucin-producing sweat gland carcinoma in a patient with metastatic melanoma

A 55-year-old male with metastatic melanoma recently off immunotherapy presented with a 1-year history of an asymptomatic, slow growing mass on his right eyelid. Examination revealed a 3-mm well-circumscribed flesh-colored papule on the right upper eyelid margin. Excision performed by oculoplastics showed a multinodular superficial cystic and deep solid dermal neoplasm. The cystic component was comprised of an epithelial lining two layers thick. The deep solid component had foci of papillary change. Lesional cells had nuclear contours with small nuceloli and sparse pale granular eosinophilic cytoplasm. Scattered mitoses were present and high-grade atypia was absent. The tumor was positive for chromogranin A, CK7, EMA, BerEp4, synaptophysin (patchy), ER, and PR. MelanA, CK20, and CD56 were negative. P63 highlighted myoepithelial cells around the tumor. Based on the histopathologic and immunohistochemical features, endocrine mucin-producing sweat gland carcinoma (EMPSGC) was diagnosed. EMPSGC is an uncommon low-grade carcinoma with histopathologic and immunohistochemical features of solid, papillary breast carcinoma. Diagnosis can be difficult given its rarity and broad clinical differential diagnosis. The key immunohistochemical feature is neuroendocrine expression; tumors also often co-express estrogen and progesterone receptors. Elaboration of a myoepithelial layer surrounding the tumor is prudent to evaluate for invasive tumor. Although EMPSGC is a low-grade carcinoma with no reported cases of metastases, complete surgical excision is recommended given local recurrence and concern for progression to invasive mucinous carcinoma. Our patient’s tumor was completely excised via Mohs micrographic surgery with closure by oculoplastics. To our knowledge, there is no known association between EMPSGC and melanoma.

28581 Vulvar mammary-like adenocarcinoma with overlying extramammary Paget disease

Observations: An 88-year old Asian female with a history of thyroid cancer presented with an itchy 5 cm erythematous inflammatory plaque on the right labia majora extending to the clitoris and left labia majora. Biopsy revealed mammary-like adenocarcinoma beneath extramammary paget disease of the vulva. Breast mammograms revealed no malignancy. The invasive dermal tumor resembled invasive ductal adenocarcinoma of the breast, being positive for cytokeratin 7 and negative for cytokeratin 20. Malignant pagetoid cells were in the epidermis. Immunohistochemical reactions found PR negative, weakly ER positive, 3+ positive for HER2, and S100 negative. Abdominal and pelvic PET/CT images revealed a hypermetabolic area only in the vulvar region. Advanced age advised against chemotherapy. The patient was treated with 4500 cGy intensity-modulated radiation therapy followed by 2160 cGy boost to the vulva and pelvic lymph nodes. A month after completion, there were no complications. She died 8 months later, cause not known.

Delayed presentation of inflammatory breast carcinoma during the COVID-19 pandemic.

BackgroundBreast cancer may present with distinct cutaneous manifestations that may be paraneoplastic or secondary to direct skin infiltration, distant skin metastases, or dermal lymphatic tumor embolization (inflammatory breast carcinoma).Case reportA 51-year-old Asian woman visited the emergency care department during the outbreak of COVID-19 in Northern Italy. About 6 months before, she had noted the onset of right breast swelling accompanied by skin redness and itching. She never consulted a physician, and, over time, the local skin condition progressed to a large scaly plaque covering the entire breast surface including the nipple. At presentation, abduction of the right upper limb was impaired due to severe shoulder pain. CT scan showed the presence of bilateral breast masses with necrotic and colliquative features, and multiple skeletal, nodal, pulmonary, and brain images suggestive of metastases. An ultrasound-guided core biopsy of the contralateral breast showed grade 2 non-special type infiltrating carcinoma. The patient was referred to the breast oncology unit and is currently being treated with aromatase inhibitors and chemotherapy.ConclusionThe COVID-19 pandemic has disrupted the entire spectrum of oncological care including breast cancer. Hopefully, telemedicine will contribute to increase patients’ confidence and will provide earlier diagnosis and treatment while minimizing the risk of contagion.

Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors.

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.

The "Matrisome" reveals the characterization of skin keloid microenvironment.

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

Dermal melanocytic tumor with CRTC1‐TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity

"Cutaneous melanocytic tumor with CRTC1-TRIM11 fusion" (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100-protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow-up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65-year-old female and the other on the arm of a 33-year-old female in addition to a comprehensive literature review are reported.

Struma ovarii-A rare entity

Struma ovarii, also known as goiter of the ovary is a rare disease.1 Considering the rarity of this tumor and constrained literature in Nepal’s context, we hereby present a case of a 46-year-old female, asymptomatic, with normal blood parameters who presented with an abdominal mass. She was suspected of malignant ovarian mass on an ultrasonogram. Intraoperative frozen section examination revealed a benign tumor suggestive of dermal tumor versus struma ovarii. Postoperatively, histopathological examination was performed to assess the percentage of thyroid tissue and a diagnosis of benign struma ovarii was made which was confirmed by thyroglobulin positivity on immunohistochemistry. No features of immature teratoma and malignancy were identified.

Mycosis fungoides and Sézary syndrome tumor cells express epidermal fatty acid-binding protein, whose expression decreases with loss of epidermotropism.

Fatty acid binding protein (FABP) is a family of transport proteins for fatty acid (FA). Epidermal FABP (E-FABP) is highly expressed by resident memory T cells (TRM ) in the skin. It supports the uptake of exogenous FA for long-term survival of skin TRM . Mycosis fungoides (MF) is regarded as malignancy of skin TRM . In this study, we investigated E-FABP expression in psoriasis vulgaris (PV), atopic dermatitis (AD), MF, and Sézary syndrome (SS). E-FABP mRNA levels in PV were much higher than those in healthy controls. E-FABP mRNA levels in AD and MF/SS lesional skin were also significantly higher than those of normal skin. By immunohistochemical staining, E-FABP was positive in MF/SS lesional skin. Interestingly, E-FABP was stained positive in epidermotropic lymphoid cells in patch, plaque, and erythrodermic lesions of MF/SS, suggesting that a part of tumor cells expressed E-FABP. In tumorous lesions, however, most dermal tumor cells were negative for E-FABP. Immunohistochemical staining using patch/plaque lesions and tumorous lesions from the same patients also revealed that E-FABP expression decreased in tumorous lesions. Our study has suggested that MF/SS tumor cells express E-FABP, whose expression decreases with loss of epidermotropism.

Efficacy of Surgical Excision and Adjuvant High-dose Rate Brachytherapy in Treatment of Keloid: Our Experience.

Background:Keloids are dermal tumors that are due to increased production of collagen caused by abnormal and prolonged wound healing. The incidence of recurrence is extremely high if only conservative measures are used. This study was conducted to evaluate the feasibility and efficacy surgery and high dose rate brachytherapy as an adjuvant therapy for treatment of keloids.Materials and Methods:50 patients with clinically diagnosed 71 keloids were treated with excision of keloid and post-operative high-dose rate brachytherapy were studied. Complete excision of the keloid till the healthy skin margin was excised. The wound were closed in 2 layers. Subcutaneous tissue closed using absorbable suture, over which a 6F flexible polyethylene tube was placed. High dose rate cobalt-60 brachytherapy was administered. Total of 15 Gy in divided dose, 5 Gy in 3 fractions were administered.Results:50 patients with 71 keloids were studied. Out of the 50 patients, 12 were male (24%) and 38 were females (76%). Age of the patients ranged between 14 and 71 years. Recurrence rate was 2% with 2 keloids recurring at 5 months interval. 4 patients scored the results as unacceptable, remaining 45 patients rated their results as excellent during their follow up at 10 days, 3 months and 6 months.Conclusion:Treatment of keloids in the plastic surgeon’s practice even today is still challenging. Many therapies have been described, but recurrence rate is high with mono-therapy. Combination therapy especially surgical excision with postoperative radiotherapy is best in preventing recurrence.

Co-expression of CD34 and h-caldesmon in a benign meningioma-like dermal neoplasm, a case report

Meningioma-like dermal tumor with diffuse coexpression of CD34 and hcaldesmon is rarely reported. Herein, we report a case of a 58-years-old woman who complained of a solitary dome-shaped papule on the left hand. An ellipse of skin measuring 1 x 0.5 x 0.5 cm was excised and sent for histopathological evaluation. Upon sectioning, the specimen showed a whitish firm dermal nodule measuring 3 mm in its greatest dimension. Microscopic examination revealed a well-circumscribed barely encapsulated dermal lesion showing compact round whorled sheets formed of round to ovoid uniform cells with abundant pink cytoplasm. Occasional intranuclear vacuoles were seen. A minor capillary-sized vascular component was seen in the background. Immunohistochemical (IHC) study revealed a diffuse positivity of tumor cells to CD34 and h-caldesmon along with faint reaction to Smooth Muscle Actin (SMA) and ER. However, Desmin, S100, HMB45, EMA, Pan Cytokeratin, and Chromogranin were all negative. Ki67 was very low (1%). The main differential diagnoses of the current lesion are meningioma and glomus family tumors. While the current lesion is morphologically reminiscent of cutaneous meningioma; neither the location nor the IHC stains support that diagnosis. The glomus family is highly suggestive. However, the location, the compact nature of the proliferation, and the positivity of CD34, all are unusual in such entities.

Dermatofibroma Over The Scar – A Rare Entity

Dermatofibroma is a common benign dermal tumour of unknown aetiology. With varied clinical presentation mimicking keloid, desmoid tumour and leiomyoma, the diagnosis of Dermatofibroma sometimes become problematic from the clinician side. Here, we report a case of Dermatofibroma in a not so common site which was clinically diagnosed to be a keloid. But later, the lesion turned out to be a dermatofibroma on histopathological examination. In our patient, the lesion was a single smooth circumscribed nodule over the left side of the abdomen. The lesion had a linear scar on either side and on palpation; it was firm in consistency. It was initially diagnosed to be a keloid which even after multiple intra-lesional steroid injections, failed to show any results. This prompted us to search for an alternate diagnosis; hence lesion was excised and analyzed. The Histopathological examination revealed a circumscribed lesion in the dermis, composed of benign spindle-shaped cells arranged in a storiform pattern. These findings, as mentioned above, were consistent with a diagnosis of Dermatofibroma, which is a slow-growing tumour commonly seen in the extremities. The keloid like a presentation of Dermatofibroma, is one another example of how a similar morphological presentation may have two distinct diagnoses resulting in a delay in providing appropriate treatment.

Spindle cell variant of epithelioid cell histiocytoma (spindle cell histiocytoma) with ALK gene fusions: Cases series and review of the literature.

Epithelioid fibrous histiocytoma (EFH) is an uncommon dermal neoplasm expressing anaplastic lymphoma kinase (ALK) protein. Rarely a histopathological variant of this entity exhibits exclusively spindle cells. We report three cases of EFH that do not completely fulfill phenotypic criteria featuring spindle cell morphology and expressing ALK protein. We also analyze the fusion partner genes rearranged with ALK in these cases. ALK expression and rearrangement status were evaluated by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next generation sequencing based gene fusion analysis. Three cases, all from females between 25 and 55 years old, have been biopsied from back, left arm, and thumb. All three cases showed tumor with exclusively spindle cell morphology without any epithelioid cells. The tumor cells exhibited strong ALK expression by IHC and FISH study confirmed ALK gene rearrangement in all three cases. DCTN1-ALK fusion was identified in two cases. EFH is not always purely epithelioid and its spindled cell variant, spindle cell histiocytoma, should be included in the differential diagnosis of superficial dermal spindled cell neoplasms. ALK immunostain is a useful diagnostic marker for this entity and further studies may be useful to investigate whether DCTN1-ALK fusion mutations are specific to EFH with spindled cell features.

真皮导管瘤一例

Dermal duct tumor arising from the intradermal portion of the eccrine duct is a variant of benign eccrine sweat duct tumor. The tumor is a rare, usually occurs on the head and neck or limbs and presents as a non-characteristic, usually asymptomatic, flesh-colored or erythematous, firm nodule or papule. Histologically, the tumor lobules are located principally in the dermis with or without connection to the epidermis, showed similar architectural features and identical cytologic features of eccrine poroma. We report a case of dermal duct tumor which developed on the left calf area in a 57-year-old male patient.

Pedunculated atypical fibroxanthomas of the face

Atypical fibroxanthomas are rare, superficial dermal tumors. Most cases are benign and only locally destructive with a low rate of metastasis. Lesions are most commonly found on sun-exposed sites of elderly light-skinned patients and present as asymptomatic nodules with irregular borders; ulcerations and friability are other key characteristics. Pedunculated lesions, however, are rarely described in the literature. We present two cases of atypical fibroxanthoma manifesting as exophytic, pedunculated lesions on the face: one in a 74-year-old man and the other in an 82-year-old woman. These tumors are very effectively treated by excision with Mohs micrographic surgery.

Dermatofibrosarcoma protuberans associated with trauma: A case report.

A case of dermatofibrosarcoma protuberans (DFSP) in a 22-year old female associated with blunt trauma of the mid-upper back is presented in the current study with a review of the literature. DFSP is a rare slow growing sarcoma of the soft tissue most commonly seen on the trunk and upper extremities with a low to intermediate grade malignant potential, high chance of local invasion and a high local recurrence rate. The literature search revealed that both non-congenital mutation as well as trauma serve a role in the development of this dermal neoplasm, but the exact mechanism by which trauma may predispose to development of DFSP is unknown. However, it seems intuitive that chronic inflammation and stimulation of the immune system at a local level may trigger the immunopathologic changes that could lead to the malignant transformation of dermal cells. Future research into the relationship between trauma and DFSP on a cellular level is required, as there appears to be a direct link present.

Carcinoma de Merkel intraepidérmico. Presentación de un caso con expresión de INSM1

We report the case of a 90-year-old male who presented with an erythematous desquamative plaque on his left cheek. Histopathology demonstrated an epidermal lesion with multifocal epithelial growth. The cells were small, with scant cytoplasm and hyperchromatic nuclei with molding and a high mitotic and apopototic rate. Immunohistochemistry showed positivity for CK20, CK7, synaptophysin and INMS1. These findings are consistent with a Merkel cell carcinoma in situ. This tumor corresponds to a primary neuroendocrine neoplasm of the skin, which usually affects elderly people with sun-exposed skin. Usually, it presents as a dermal tumor but intraepidermal involvement alone is extremely rare. In this scenario, a broad differential diagnosis should be considered, excluding all neoplasms that may present intraepidermal forms. The evolution of this entity is unknown.

Cutaneous leiomyosarcoma /
 atypical smooth muscle sarcoma

Relevance: Cutaneous leiomyosarcoma is a rare primary
 dermal neoplasm, accounting for up to 2-3% of all superficial
 sarcomas. It can occur at any age, most likely between the ages
 of 50 and 70 years. This tumor has a high recurrence potential
 in case of insufficiently deep excision. Recurrent tumors are
 more aggressive and characterized by subsequent metastasis.
 The purpose of the study was to demonstrate the results
 of the histopathological examination of a cutaneous leiomyosarcoma / atypical smooth muscle tumor.
 Results: Cutaneous leiomyosarcoma was represented by
 spindle-shaped cells with high cellularity located in bundles
 and growing expansively, surrounded by a capsule. The nuclei
 of the cells were elongated, hyperchromic. Cells with atypical
 abnormal nuclei were present in smaller quantities. The mitoses, including atypical, were numerous. IHC staining for SMA,
 Desmin, H-Caldesmon – diffusely positive on tumor cells. The
 reaction for S100, Myogenin – negative.
 Conclusion: A cutaneous leiomyosarcoma can be finally
 diagnosed only after a pathomorphological examination of
 the specimen and differential diagnostics using additional research methods.