Dermatopathology, Volume 11, Issue 1 (March 2024) – 13 articles

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the implementation of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs. (2) Methods: Single-center retrospective study in patients with ADRs after mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines). (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculopapular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular predominantly lymphocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred after the second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% of patients and maculopapular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients. (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. Interestingly, in about half of our patients, ADRs were self-limited, whereas ADRs extended beyond a month in the other half. Full article

As the Editor-in-Chief of Dermatopathology and the President of the European Society of Dermatopathology (ESDP), I have the great pleasure of celebrating the 10th anniversary of Dermatopathology, the only online journal in the field of cutaneous pathology and the official journal of the ESDP [...] Full article

This case report describes a case of a patient with MUTYH-associated polyposis (MAP), who presented with multiple sebaceomas in a Muir–Torre-like phenotype. MAP is caused by mutations in MUTYH, a base excision repair gene responsible for detecting and repairing the 8-oxo-G:A transversion caused by reactive oxygen species. MAP is associated with an increased risk of developing adenomatous polyps and colorectal cancer. Muir–Torre syndrome is a clinical phenotype of Lynch syndrome, which presents with multiple cutaneous sebaceous neoplasms. Lynch syndrome, like MAP, increases the likelihood of developing colorectal cancer but with a different pathogenesis and mode of inheritance. This case demonstrates that in a patient presenting with multiple sebaceous neoplasms, further workup and genetic testing may be indicated, not only for Muir–Torre and Lynch syndrome but also for MAP. Full article

In recent years, particular interest has developed in molecular biology applied to the field of dermatopathology, with a focus on nevi of the Spitz spectrum. From 2014 onwards, an increasing number of papers have been published to classify, stratify, and correctly frame molecular alterations, including kinase fusions. In this paper, we try to synthesize the knowledge gained in this area so far. In December 2023, we searched Medline and Scopus for case reports and case series, narrative and systematic reviews, meta-analyses, observational studies—either longitudinal or historical, case series, and case reports published in English in the last 15 years using the keywords spitzoid neoplasms, kinase fusions, ALK, ROS1, NTRK (1-2-3), MET, RET, MAP3K8, and RAF1. ALK-rearranged Spitz tumors and ROS-1-rearranged tumors are among the most studied and characterized entities in the literature, in an attempt (although not always successful) to correlate histopathological features with the probable molecular driver alteration. NTRK-, RET-, and MET-rearranged Spitz tumors present another studied and characterized entity, with several rearrangements described but as of yet incomplete information about their prognostic significance. Furthermore, although rarer, rearrangements of serine–threonine kinases such as BRAF, RAF1, and MAP3K8 have also been described, but more cases with more detailed information about possible histopathological alterations, mechanisms of etiopathogenesis, and also prognosis are needed. The knowledge of molecular drivers is of great interest in the field of melanocytic diagnostics, and it is important to consider that in addition to immunohistochemistry, molecular techniques such as FISH, PCR, and/or NGS are essential to confirm and classify the different patterns of mutation. Future studies with large case series and molecular sequencing techniques are needed to allow for a more complete and comprehensive understanding of the role of fusion kinases in the spitzoid tumor family. Full article

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. Full article

Galli–Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD’s first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the KRT5 and POGLUT1 genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments. Full article

Ulcerations of the lower extremities are a frequently encountered problem in clinical practice and are of significant interest in public health due to the high prevalence of underlying pathologies, including chronic venous disease, diabetes and peripheral arterial occlusive disease. However, leg ulcers can also present as signs and symptoms of various rare diseases and even as an adverse reaction to drugs. In such cases, correct diagnosis ultimately relies on histopathological examination. Apart from the macroscopic presentation, patient history and anatomic location, which are sometimes indicative, most ulcers have very distinct histopathological features. These features are found in different layers of the skin or even associated vessels. In this narrative review, we discuss and highlight the histopathological differences of several types of leg ulcers that can contribute to efficient and accurate diagnosis. Full article

Direct immunofluorescence is a vital diagnostic test for assessing vesiculobullous disorders, vasculitides, and connective tissue diseases. It is a robust and valuable technique that offers essential diagnostic information for many critical dermatoses. Dermatopathologists depend heavily on the data obtained from direct immunofluorescence evaluation to confirm final diagnoses. Selecting the most appropriate biopsy site is necessary for maximizing diagnostic accuracy, and the best site may vary depending on the clinical differential diagnosis. Inaccurate biopsy site selection can significantly impact the accuracy of the results. To optimize the use of direct immunofluorescence studies, this review provides helpful guidelines and some practical tips for selecting the best biopsy site. Full article

Over the past decade, molecular and genomic discoveries have experienced unprecedented growth, fundamentally reshaping our comprehension of melanocytic tumors. This review comprises three main sections. The first part gives an overview of the current genomic landscape of cutaneous melanocytic tumors. The second part provides an update on the associated molecular tests and immunohistochemical stains that are helpful for diagnostic purposes. The third section briefly outlines the diverse molecular pathways now utilized for the classification of cutaneous melanomas. The primary goal of this review is to provide a succinct overview of the molecular pathways involved in melanocytic tumors and demonstrate their practical integration into the realm of diagnostic aids. As the molecular and genomic knowledge base continues to expand, this review hopes to serve as a valuable resource for healthcare professionals, offering insight into the evolving molecular landscape of cutaneous melanocytic tumors and its implications for patient care. Full article

Folliculosebaceous cystic hamartoma (FSCH) is a rare and benign form of cutaneous hamartomas. These skin lesions often lead to clinical and histopathological misdiagnosis due to their similarities to cutaneous lesions with overproduction of clustered sebaceous glands. Clinically, the lesions often present as solitary, skin-colored, pedunculated warts to cauliflower-like, exophytic papules and nodules, usually with a diameter ranging 0.5–1.5 cm that rarely exceed 2 cm in size. Only a small number of giant variants are reported in the literature with a diameter in the range of 5–23 cm. The vast majority of the lesions appear in the central face and show a striking predilection for the nose, ears, and scalp, but also emerge on the nipples, extremities, and genitals. Histologically, the epithelial components of folliculosebaceous cystic hamartoma comprise dilated infundibular cystic proliferation with surrounding mesenchymal components, which commonly include fibroplasia and vascular and adipose tissue proliferation. These histological characteristics were coined by Kimura and colleagues (1991). To the best of our knowledge, our case represents the biggest variant of giant folliculosebaceous cystic hamartoma. Full article

We present the case of a 99-year-old Caucasian female who was referred for treatment of a painless, 8.0 cm × 7.8 cm exophytic, pedunculated, ulcerated tumor of the left medial canthus. Pathology showed spindled, oval, and polygonal cells with pleomorphic nuclei. Many multinuclear giant cells and mitotic figures were also noted. The tumor was highlighted with CD10, showed focal positivity with actin, desmin, and CD68, and had increased Ki67 immunohistochemical staining. The tumor was negative for pancytokeratin, CK5/6, p63, MART-1/MelanA, S100, Sox10, p40, CD34, and CD23. Based on clinicopathologic correlation, the diagnosis of pleomorphic dermal sarcoma (PDS) was made. Pleomorphic dermal sarcoma (PDS) refers to a deep, histologically high-grade tumor that often resembles other tumors clinically and histologically. As PDS is frequently aggressive and related to adverse outcomes, it is important to recognize its distinguishing features in comparison to other similar entities, including atypical fibroxanthoma (AFX) and pleomorphic leiomyosarcoma (PLMS). To our knowledge, there is only one other reported case in the literature of PDS occurring on the eye. By reviewing and understanding characteristic etiologies, locations of presentation, histopathological features, and management techniques, pathologists can make a more accurate diagnosis and dermatologists can provide more effective patient care in a timely manner. Full article

A 31-year-old male presented with a firm, well-demarcated, erythematous, crateriform, and ulcerated nodule in the left lumbar region, which persisted for 3 months. Clinically, a keratoacanthoma was suspected. The histological analysis was consistent with perforating fibrous histiocytoma, a rare histopathologic variant of fibrous histiocytoma. To our knowledge, this is the third case reported in the literature. Full article

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey–Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism. Full article