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1.
Skin Health Dis ; 4(2): e325, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38577055

ABSTRACT

Epidermolytic hyperkeratosis is a rare histopathological phenomenon which has been reported in a number of dermatological conditions. It is rare but can cause chronic and intractable symptoms which can impede the quality of life of those affected. Treatment options are variable and not enough data exists to provide a definitive protocol for management. We present this case to highlight a simple, efficacious way for dermatologists to treat the condition and provide a literature review.

2.
Dermatopathology (Basel) ; 11(1): 101-111, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38390851

ABSTRACT

This literature review introduces the integration of Large Language Models (LLMs) in the field of dermatopathology, outlining their potential benefits, challenges, and prospects. It discusses the changing landscape of dermatopathology with the emergence of LLMs. The potential advantages of LLMs include a streamlined generation of pathology reports, the ability to learn and provide up-to-date information, and simplified patient education. Existing instances of LLMs encompass diagnostic support, research acceleration, and trainee education. Challenges involve biases, data privacy and quality, and establishing a balance between AI and dermatopathological expertise. Prospects include the integration of LLMs with other AI technologies to improve diagnostics and the improvement of multimodal LLMs that can handle both text and image input. Our implementation guidelines highlight the importance of model transparency and interpretability, data quality, and continuous oversight. The transformative potential of LLMs in dermatopathology is underscored, with an emphasis on a dynamic collaboration between artificial intelligence (AI) experts (technical specialists) and dermatopathologists (clinicians) for improved patient outcomes.

3.
J Cutan Pathol ; 51(4): 267-271, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38140907

ABSTRACT

Sclerotic fibroma (SF) is a rare subset of dermal fibromas that occurs sporadically or in association with Cowden syndrome (CS). We report a case of a patient with known CS and a solitary lesion on the scalp. Histologic examination demonstrated a well-circumscribed lesion with sclerotic dermis and a whorled collagen pattern, multinucleated giant cells, and dendritic spindle cells. Nuclear atypia or mitotic figures were not noted. The giant cells were negative for Melan-A, SOX-10, EMA, SOX-10, and factor XIIIa. These findings are consistent with a giant cell collagenoma (GCC). Despite possible overlap with SF, GCC has not been associated with CS. This makes our case unique and suggests that GCC should be included in the spectrum of CS-associated cutaneous lesions. The diagnosis of SF may lead to the identification of previously undiagnosed CS; accordingly, GCC, even when present as a solitary lesion, may indicate the need for further work-up and screening for CS.


Subject(s)
Fibroma , Hamartoma Syndrome, Multiple , Nevus , Skin Diseases , Skin Neoplasms , Humans , Hamartoma Syndrome, Multiple/diagnosis , Skin Neoplasms/pathology , Fibroma/complications , Fibroma/pathology , Skin Diseases/pathology , Giant Cells/pathology
4.
Am J Dermatopathol ; 45(10): 721-723, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37708370

ABSTRACT

ABSTRACT: Cervical chondrocutaneous branchial remnant is a rare congenital developmental anomaly typically located on the lateral neck. Histologically, it has the appearance of an accessory tragus demonstrating a central cartilaginous core with surrounding fibrosis located in the subcutaneous tissue. The condition has been associated with a variety of congenital anomalies, particularly involving the auditory, cardiovascular, and visual systems. Given that research-based evidence related to cervical chondrocutaneous branchial remnant in dermatology literature is sparse, we present this case to raise more awareness about this entity among dermatopathologists and review the different histopathologic presentations and possible associated anomalies.


Subject(s)
Neck , Subcutaneous Tissue , Humans , Subcutaneous Fat
6.
Melanoma Res ; 33(4): 283-292, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37276030

ABSTRACT

Melanoma is a highly aggressive form of skin cancer and the most frequent lethal malignancy diagnosed by dermatologists. Although there have been advances for predicting melanoma prognosis, there are few highly sensitive and specific diagnostic tools for clinically evaluating suspicious melanocytic lesions prior to biopsy. We have recently determined that alterations in cellular lipid and pigment content are associated with tumor progression and melanoma metastasis. Here, we seek to determine if lipid droplet and pigment content assessments near the skin's surface are able to distinguish benign from malignant melanocytic lesions. We obtained 14 benign melanocytic lesions, classified as Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) class 1, and 22 malignant melanomas, classified as MPATH-Dx class 4 or 5, from Boston Medical Center. The malignant melanomas had an average greatest thickness of 1.8 ±â€…2.1 mm with 7/22 biopsies showing the presence of ulceration. Tissues were stained with the Fontana Masson stain to detect pigment or immunohistochemically stained for adipophilin, the main protein component of lipid droplets, to detect lipid droplets. Pigment and lipid droplets were quantified using ImageJ and CellProfiler, respectively. We found no significant difference in total pigment area between benign melanocytic lesions and malignant melanoma, and a 66% decrease in lipid content and 68% reduction in lipid/pigment content between benign melanocytic lesions and malignant melanoma ( P  < 0.05). Our results suggest that lipid content and lipid/pigment content ratios may distinguish benign and malignant melanocytic lesions, which may be useful as a diagnostic tool for histopathologically challenging pigmented lesions.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/diagnosis , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Melanocytes/pathology , Prognosis , Lipids
7.
Dermatopathology (Basel) ; 9(4): 355-360, 2022 Oct 20.
Article in English | MEDLINE | ID: mdl-36278542

ABSTRACT

Clear cell acanthoma (CCA) is classically considered a benign epidermal tumor, although rare case reports have described CCA with malignant features. Here, we present a case of a patient with a biopsy proven CCA that regrew post-biopsy and was subsequently completely excised. Histologic examination of the tumor in the excision specimen revealed malignant cytologic features that were not present in the initial biopsy. A review of the literature identified five additional cases of CCA with similar malignant cytologic features. On analysis, common histopathologic characteristics included cellular pleomorphism, increased nuclear-to-cytoplasmic ratio, prominent nucleoli, and atypical mitotic figures. We support the designation of atypical clear cell acanthoma for these entities with features of both CCA and significant cytologic atypia. As none of these cases exhibited clinically aggressive behavior, further study is warranted.

9.
Dermatopathology (Basel) ; 9(3): 244-250, 2022 Jul 05.
Article in English | MEDLINE | ID: mdl-35892481

ABSTRACT

Pityriasis lichenoides is an acute and/or chronic skin disease associated with recurrent erythematous papules that self-resolve. While its etiology is unknown, preceding viral infection may play a role. We present an atypical case of a 40-year-old woman with pityriasis lichenoides et varioliformis acuta as a complication of a COVID-19 infection.

10.
J Dermatol ; 49(11): 1193-1197, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35906811

ABSTRACT

Melanocytic matricoma is a rarely reported, benign cutaneous adnexal neoplasm composed of epithelial cells exhibiting differentiation towards hair matrix as well as admixed, pigmented, dendritic melanocytes. The proposed malignant counterpart to melanocytic matricoma, malignant melanocytic matricoma (MMM), is even more rare. Here we report a case of a melanocytic matricoma with atypical features in a 92-year-old female with a 1.2-cm pigmented nodule on the right nasal sidewall. Histopathology revealed a well-circumscribed dermal tumor composed of atypical matrical cells with scattered aggregates of anucleate keratinocytes (ghost cells), prominent intratumoral pigment, numerous mitotic figures (88 mitosis/10 high-power field [HPF]), and intermixed dendritic melanocytes. A literature review was performed for MMM to determine if the current case fit diagnostic criteria for this entity. Including the current case, 12 cases of MMM were identified and analyzed to investigate common clinical and histopathologic features. MMM commonly occurred on the head and neck (7/12 cases) of older individuals (median age of 80) with a slight male predominance (male-to-female ratio of 3:1) and on histopathology presented as a multinodular dermal tumor composed of mitotically active (average mitotic rate of >50 mitoses/10 HPF) pleomorphic epithelial cells with foci of ghost cells. Dendritic melanocytes were found throughout the tumor lobules in all cases. Given that only two of 12 cases have exhibited locally aggressive behavior, further study is warranted to determine the true malignant potential of MMM.


Subject(s)
Hair Diseases , Neoplasms, Adnexal and Skin Appendage , Pilomatrixoma , Skin Neoplasms , Male , Female , Humans , Aged, 80 and over , Pilomatrixoma/pathology , Hair Diseases/pathology , Skin Neoplasms/pathology , Neoplasms, Adnexal and Skin Appendage/pathology , Melanocytes/pathology
11.
Am J Dermatopathol ; 44(3): 174-178, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35171884

ABSTRACT

ABSTRACT: Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) can often demonstrate clinical and histopathologic overlap. A recent study demonstrated significant plasmacytoid dendritic cell (pDC) recruitment in lesions of PLEVA, whereas another study reported minimal pDC recruitment in lesions of LyP. To confirm the possible diagnostic value of pDCs in differentiating PLEVA and LyP, we compared the presence and distribution of pDCs and myxovirus protein A (MxA) expression (an indirect assessment of pDC activity). In total, 19 cases of PLEVA (16 patients) and 14 cases of LyP (11 patients) were examined using immunohistochemical stains for anti-blood-derived dendritic cell antigen-2 and MxA. Individual semiquantitative scoring systems were used to assess the immunohistochemical results, and a Mann-Whitney test with a subsequent 2-tailed P test was performed for statistical analysis. No statistically significant difference in the number of pDCs in both groups was found. However, most PLEVA cases (84%) demonstrated intense and diffuse MxA expression, whereas LyP cases (71%) demonstrated weak patchy staining (P < 0.007). Our study suggests that although additional studies may be needed to determine whether pDCs are more relevant to the pathogenesis of PLEVA or LyP, pDC activity through MxA staining may play a role in differentiating PLEVA from LyP and may serve as a platform for additional studies.


Subject(s)
Dendritic Cells/pathology , Lymphomatoid Papulosis/pathology , Pityriasis Lichenoides/pathology , Adult , Diagnosis, Differential , Female , Humans , Male , Retrospective Studies
12.
Am J Dermatopathol ; 44(2): e23-e25, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35076434

ABSTRACT

ABSTRACT: Three hundred thousand new cases of Lyme disease are diagnosed annually in the United States. The earliest manifestation of the disease, erythema migrans, occurs earlier than serologic conversion, and skin biopsies can be very helpful in suggesting the diagnosis. Histopathologic findings vary depending on where in the lesion the specimen is taken, but typically consist of a superficial and deep perivascular and interstitial lymphocytic infiltrate with eosinophils centrally and with histiocytes and plasma cells at the periphery. Rare cases with interstitial histiocytes and rare-to-sparse plasma cells exist. We present a 67-year-old man whose skin biopsy, taken on day 2 of his eruption, demonstrated a subtle perivascular and interstitial infiltrate of histiocytes without plasma cells. Dermatopathologists need to be aware of this pattern and consider the diagnosis of erythema migrans, despite negative initial serologic testing.


Subject(s)
Erythema Chronicum Migrans/pathology , Plasma Cells/pathology , Aged , Borrelia burgdorferi/isolation & purification , Erythema Chronicum Migrans/diagnosis , Humans , Male
13.
Am J Dermatopathol ; 44(4): 297-301, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34726189

ABSTRACT

ABSTRACT: A 50-year-old man, with a history of extensive sun exposure and multiple previous non-melanoma skin cancers, presented with an asymptomatic 8-× 10-millimeter scaly, skin-colored papule on his right shoulder. Subsequent biopsy and excision revealed epidermal hyperplasia containing large atypical basaloid cells with pagetoid spread. Immunoperoxidase staining for cytokeratin-20 demonstrated a focal perinuclear dot-like pattern, and after excluding other in situ entities, a diagnosis of Merkel cell carcinoma In Situ (MCCIS) was rendered. MCCIS is a very rare entity. Although approximately 18% of Merkel cell carcinomas have epidermal involvement, currently only 17 cases of MCCIS have been reported, of which only 7 had no associated neoplasm. Previously, MCCIS was considered a serendipitous or incidental finding, as most cases co-existed with squamous cell carcinoma in situ. This case is unique in that it was not associated with a squamous lesion, and in addition, the pagetoid spread was unusual and has only occasionally been described. As such, MCCIS should be added to list of in situ epidermal lesions with pagetoid spread.


Subject(s)
Carcinoma, Merkel Cell/diagnosis , Skin Neoplasms/diagnosis , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/surgery , Diagnosis, Differential , Humans , Male , Middle Aged , Skin Neoplasms/pathology , Skin Neoplasms/surgery
14.
Cancer Res ; 81(8): 2071-2085, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33526511

ABSTRACT

The failure of once promising target-specific therapeutic strategies often arises from redundancies in gene expression pathways. Even with new melanoma treatments, many patients are not responsive or develop resistance, leading to disease progression in terms of growth and metastasis. We previously discovered that the transcription factors ETS1 and PAX3 drive melanoma growth and metastasis by promoting the expression of the MET receptor. Here, we find that there are multiple ETS family members expressed in melanoma and that these factors have redundant functions. The small molecule YK-4-279, initially developed to target the ETS gene-containing translocation product EWS-FLI1, significantly inhibited cellular growth, invasion, and ETS factor function in melanoma cell lines and a clinically relevant transgenic mouse model, BrafCA;Tyr-CreERT2;Ptenf/f. One of the antitumor effects of YK-4-279 in melanoma is achieved via interference of multiple ETS family members with PAX3 and the expression of the PAX3-ETS downstream gene MET. Expression of exogenous MET provided partial rescue of the effects of YK-4-279, further supporting that MET loss is a significant contributor to the antitumor effects of the drug. This is the first study identifying multiple overlapping functions of the ETS family promoting melanoma. In addition, targeting all factors, rather than individual members, demonstrated impactful deleterious consequences in melanoma progression. Given that multiple ETS factors are known to have oncogenic functions in other malignancies, these findings have a high therapeutic impact. SIGNIFICANCE: These findings identify YK-4-279 as a promising therapeutic agent against melanoma by targeting multiple ETS family members and blocking their ability to act as transcription factors.


Subject(s)
Indoles/pharmacology , Melanoma/drug therapy , Proto-Oncogene Proteins c-ets/antagonists & inhibitors , Skin Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/metabolism , Disease Progression , Humans , Melanoma/metabolism , Melanoma/pathology , Mice , Mice, Transgenic , Neoplasm Invasiveness , Oncogene Proteins, Fusion/antagonists & inhibitors , PAX3 Transcription Factor/antagonists & inhibitors , PAX3 Transcription Factor/metabolism , Proto-Oncogene Protein c-ets-1/antagonists & inhibitors , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-fli-1/antagonists & inhibitors , Proto-Oncogene Proteins c-ets/metabolism , Proto-Oncogene Proteins c-met/antagonists & inhibitors , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , RNA-Binding Protein EWS/antagonists & inhibitors , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism
15.
Front Med (Lausanne) ; 7: 314, 2020.
Article in English | MEDLINE | ID: mdl-32760731

ABSTRACT

Background: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed "driver mutations," are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors reveals cancer-related genomic alterations and provides therapeutic recommendations for specific targeted therapy. We analyzed our experience with FoundationOne, a validated NGS genomic profiling test, in a community oncology network. Methods: NGS results from May 2014 to September 2016 from a community oncology network in Western Pennsylvania were analyzed. Medical records were reviewed for primary site, stage, biopsy site, time of testing, prior treatment, FDA-approved therapy in patient's and other tumor types and potential clinical trials based upon mutations detected. Two co-primary endpoints for this study were to determine the percentage of patients having mutations with a FDA-approved targeted agent and the percentage of patients in whom a treatment decision was made based on these NGS results. Results: One Fifty-Seven NGS results were available for analysis. 82% patients had a mutation with a FDA-approved targeted agent available while 18% patients had no FDA-approved targeted agent for the mutation detected. Clinical trials were available for 93% cases. The NGS results were utilized in treatment decisions in 18% patients (n = 28) with, 7% (n = 11) initiating a targeted agent, 6% (n = 9) were on an appropriate targeted agent prior to testing and 5% (n = 8) being unable to start a targeted agent because of insurance denial, clinical deterioration or patient preference. 38% cases were tested early in the disease course (at diagnosis, during or shortly after first-line treatment) and 62% at progression. Conclusions: NGS is a valuable tool to identify molecular targets for personalizing cancer care. From our experience, the actual number of patients starting a targeted agent based on NGS results is low but it provides substantial information in terms of providing additional treatment options, identifying resistance conferring mutations and facilitating clinical trial enrollment. Optimal time of testing, early or late in disease course, financial implications of testing and using targeted therapy and survival benefit of targeted therapy need further studies.

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