Toxic epidermal necrolysis-like cutaneous toxicity following chimeric antigen receptor T-cell therapy in recurrent large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.

A case of diagnostic uncertainty: High-grade melanocytoma versus balloon cell melanoma in a pediatric patient.

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.

Myelodysplasia cutis and VEXAS syndrome initially diagnosed as histiocytoid Sweet syndrome: A diagnostic pitfall.

Histiocytoid Sweet syndrome (H-SS) is a histopathological variant of Sweet syndrome (SS) defined by cutaneous infiltration of immature myeloid cells morphologically resembling histiocytes. The association of H-SS with underlying malignancy, particularly myelodysplastic syndromes, is well-established. Myelodysplasia cutis (MDS-cutis) has been proposed to describe cases historically diagnosed as H-SS but characterized by shared clonality of the myeloid infiltrate in skin and bone marrow. Therefore, identifying patients who might have MDS-cutis is critical for the management of the associated hematologic malignancy. VEXAS syndrome, an adult-onset autoinflammatory disease, should also be included in the histopathologic differential diagnosis of H-SS, as it shares clinical and pathologic features with MDS-cutis. Through the presentation of two cases, we aim to highlight the defining features and key clinical implications of MDS-cutis and VEXAS syndrome.

Digital dermatopathology implementation: Experience at a multisite academic institution.

BACKGROUND: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change. METHODS: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis. RESULTS: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration. CONCLUSIONS: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

Dense Lichenoid Inflammation in Paget Disease: A Diagnostic Pitfall.

ABSTRACT: Mammary Paget disease is a rare form of breast cancer, which typically presents as an eczematous plaque on the nipple or surrounding skin. It is often a clinical diagnosis that is confirmed with skin biopsy. Histologic hallmarks of mammary Paget disease include large, pleomorphic, malignant, ductal epithelial cells within the epidermis. Chronic lichenoid inflammation may be seen in the papillary dermis but is not diagnostic. Because mammary Paget disease often overlies ductal carcinoma in situ or invasive carcinoma of the breast, prompt bilateral mammography is warranted. We report a case of Paget disease of the nipple with negative breast imaging that was originally misdiagnosed due to a dense lichenoid infiltrate obscuring the neoplasm.

Plexiform neurofibroma masquerading as a giant congenital melanocytic nevus.

A 4-month-old male presented for a large, hypertrichotic brown patch on the upper back with several scattered 0.5-1.5 cm, round to oval, brown macules and patches on the trunk and extremities. The lesion was initially diagnosed as a giant congenital melanocytic nevus based on clinical exam and histopathology with immunohistochemical stains. The patient was later diagnosed with neurofibromatosis type 1, and the lesion on the back developed a "bag of worms" texture consistent with a plexiform neurofibroma and found to harbor a pathogenic variant in the NF1 gene. This case highlights the diagnostic challenge of differentiating these lesions and their overlapping clinical and histopathological features.

Clinical and histopathological features of hypereosinophilic syndrome with cutaneous involvement: The Mayo Clinic Experience.

BACKGROUND: Hypereosinophilic syndrome (HES) encompasses a group of diseases with blood hypereosinophilia and eosinophil-mediated organ dysfunction. HES-associated skin abnormalities, termed cutaneous HES (cHES) here, may influence diagnosis of HES. We sought to better define clinical and histopathological features of cHES. METHODS: We retrospectively reviewed clinical records and cutaneous histopathology of adult patients with HES evaluated at our institution from 2007 to 2018. RESULTS: Forty-one percent (61/150) patients with HES had cHES. The most common clinical morphologies were urticarial (30%) and eczematous (26%). Skin specimens most often showed a spongiotic pattern (31%) with abundant inflammation (50%) including eosinophils (85%). Two specimens (8%) showed interstitial granulomatous dermatitis, and two specimens showed eosinophilic fasciitis (8%). Vasculitis was not identified in any specimen. Eighty-four percent of patients with cHES had ≥1 other organ system involved: pulmonary 41%, ENT 26%, and nervous 23%. Sixty percent (53/89) of non-cHES patients had at least two organ systems involved. Cardiac or gastrointestinal involvement was more common in non-cHES than cHES (p < 0.05). CONCLUSION: Our review confirms that there are no specific clinical or histopathological cHES patterns, but HES should be considered in patients who have eczematous or urticarial reactions of unknown etiology and persistent peripheral hypereosinophilia.

The Role of Excision for Treatment of Chromoblastomycosis: A Cutaneous Fungal Infection Frequently Mistaken for Squamous Cell Carcinoma.

BACKGROUND: Chromoblastomycosis is an uncommon fungal infection of the skin caused by a variety of dematiaceous fungal species that is typically contracted through direct inoculation into the skin. OBJECTIVE: To collect and examine data pertaining to the clinical presentation and management of patients with chromoblastomycosis. METHODS: Through a retrospective study, a pathology medical record search was performed from January 2004 to December 2020 at a single institution. RESULTS: A total of 9 patients were identified. Seven of 9 cases occurred in solid organ transplant recipients. All cases were located on the extremities. Six of 9 cases were clinically suspected to be squamous cell carcinoma. Seven of 9 cases were treated with surgical excision. Six of 9 patients were treated with oral antifungal medication. Four of 9 patients had received combination therapy. Eight of 9 patients had no recurrence of the disease after treatment. CONCLUSION: Chromoblastomycosis presents as verrucous papules or nodules and may clinically and histopathologically mimic squamous cell carcinoma. Immunosuppression is likely a risk factor for the development of chromoblastomycosis. This study highlights the importance of clinical awareness of this disease's clinical presentation and prevalence in immunosuppressed patient populations.

Eruptive Papules as a Cutaneous Manifestation of Metastatic Prostate Adenocarcinoma.

ABSTRACT: Cutaneous metastasis from prostate cancer is a rare manifestation, occurring in less than 1% of all cases of prostate cancer. Prostate cancer metastasis occurs most often in lymph nodes and bones. In this study, we present the case of a 55-year-old man with prostate adenocarcinoma and progressive papules on his left chest that developed shortly after androgen deprivation therapy was initiated. This case emphasizes the significance of considering cutaneous metastasis in the diagnostic differential when assessing patients with a history of cancer and the need to thoroughly evaluate these cases.

Deep learning for dermatologists: Part II. Current applications.

Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.

Deep learning for dermatologists: Part I. Fundamental concepts.

Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In 2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.

Cutaneous metastases of non-cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases.

BACKGROUND: Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are rare; however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management. METHODS: We performed a retrospective review from September 1, 2010 to September 30, 2020 of the histopathologic, immunohistochemical, and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non-cutaneous primaries. RESULTS: Fourteen patients were identified for the study (nine males and five females; mean age of 59.5 years). Fifteen skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non-cutaneous neuroendocrine neoplasm was present in 50% of patients. Primary sites of neuroendocrine carcinoma included lung (n = 5), terminal ileum (n = 2), and one each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). Eleven of fourteen patients are dead of disease; one was lost to follow-up. All 15 specimens showed subcutaneous/deep dermal involvement with six involving the papillary dermis and one involving the epidermis. The tumors ranged from well to poorly differentiated. Two of fifteen specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF-1 was performed in 13 specimens and was positive in six, of which two were of non-pulmonary origin. CONCLUSIONS: While immunohistochemical stains, in particular CK20, CK7, and TTF-1, are integral in the workup of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non-specific for a single primary site. Therefore, complete radiologic imaging as well as clinical correlation should be recommended to further aid in the identification of a non-cutaneous primary neoplasm.

Lichen Planus Pemphigoides Associated With PD-1 and PD-L1 Inhibitors: A Case Series and Review of the Literature.

ABSTRACT: Immune checkpoint inhibitors are increasingly being used in the treatment of various solid organ and hematologic malignancies. Dermatologic toxicities associated with programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) therapy have been widely reported in the literature. It is important for clinicians to be aware of these toxicities to ensure prompt recognition and treatment. Herein, we present the clinical, histopathologic, and immunofluorescence findings of 3 patients diagnosed with lichen planus pemphigoides (LPP) after treatment with anti-PD-1 inhibitors. We also reviewed the literature and summarize 7 previously reported cases of LPP associated with anti-PD-1 and anti-PD-L1 inhibitors. LPP was diagnosed at a median time of 24.4 weeks (range: 4-78 weeks) after initiation of immunotherapy. Clinical findings included papules, plaques, erosions, vesicles, and bullae on the trunk and extremities. Oral involvement was present in half the cases. Histopathologic features of immunotherapy-induced LPP included lichenoid or vacuolar interface dermatitis, the presence of eosinophils, and subepidermal bullae. Direct immunofluorescence demonstrated linear deposition of immunoglobulin G (IgG) or C3. Indirect immunofluorescence demonstrated linear IgG along basement membrane zone on monkey esophagus in 2 cases and linear IgG on the epidermal side of salt split skin in 3 cases. Serum anti-BP180 was elevated in all cases in which enzyme-linked immunosorbent assay was performed.

Rituximab-Induced Alopecia Universalis in a Patient With Bullous Pemphigoid.

Alopecia areata is a CD8+ T-lymphocyte driven autoimmune disorder leading to reversible hair loss. While most commonly presenting as isolated well-demarcated non-cicatricial alopecic patches on the scalp, subtypes of alopecia areata include alopecia totalis with loss of all scalp hair and alopecia universalis with complete loss of all body hair. Although primarily an idiopathic condition, several triggers, including medications, have been reported in the literature. To the best of our knowledge, we present the first reported case of rituximab, a chimeric anti-CD20 receptor monoclonal antibody, inducing alopecia universalis on two separate occasions during the treatment of bullous pemphigoid in a 55-year-old female. While the exact mechanism driving this association remains unclear, greater insights into the pathophysiology of alopecia areata/universalis may help to further explain this association and provide greater insight into other possible therapeutic options.J Drugs Dermatol. 2022;21(8):894-895. doi:10.36849/JDD.6690.

Post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified in a pediatric patient.

Solid organ and hematopoietic stem cell transplantation may be complicated by the development of post-transplant lymphoproliferative disorders (PTLDs). The World Health Organization categorizes PTLDs into four entities including non-destructive, monomorphic, polymorphic, and classical Hodgkin lymphoma types. The most common PTLDs are B-cell lymphomas, with T-cell lymphomas accounting for only a few cases. Cutaneous T-cell lymphomas are rarer still in post-transplant patients with primary cutaneous peripheral T-cell lymphoma being an extraordinarily rare subtype in this population. PTLDs may be aggressive and are often associated with high morbidity and mortality. Advances in medicine have led to increased awareness of PTLDs and improved diagnostic tools which assist in the diagnosis of these conditions. However, the clinical and histopathologic heterogeneity of PTLDs may make diagnosis a challenge. In the transplant patient population, the cutaneous manifestations of the lymphoproliferative disease may mimic other conditions, such as eczematous dermatitis and graft-vs-host disease. Herein, we report a case of post-transplant primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in a pediatric heart transplant patient and describe the clinical presentation and diagnostic histopathologic features.

Histopathologic Spectrum of Morphea.

ABSTRACT: Morphea is an autoimmune skin disease with protean clinical manifestations. Histologic features are similarly variable, and skin biopsies may be nondiagnostic. A single-institution retrospective cohort study was conducted. Morphea patients who had a biopsy in 2005-2015 were included, and a histopathological review was conducted by 2 pathologists. There were 51 biopsy specimens from 40 subjects. The most common histologic features were dermal sclerosis (90%), dermal thickening (78%), collagen homogenization (86%), a superficial and deep infiltrate (76%), a moderate-abundant inflammatory infiltrate (73%), and periadnexal fat loss/decreased skin appendages (71%). Twenty-four specimens were not diagnostic of morphea. In these specimens, the main clues to diagnosis included the presence of dermal sclerosis (79%), subtle collagen homogenization (75%), dermal thickening (58%), moderate-to-abundant plasma cells (50%), and perineural inflammation (50%). There were no statistically significant differences between active and inactive lesions, nor untreated and treated lesions. The histopathologic features of morphea are variable and a high proportion of biopsies are not diagnostic. Clinicians and pathologists should have a high degree of suspicion to correctly make the diagnosis of morphea.

Acneiform Presentations of Folliculotropic Mycosis Fungoides.

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders. However, we describe distinctive presentations of FMF with acneiform features that can be diagnostically challenging, leading to diagnostic delay. OBJECTIVE: To highlight the importance of histopathologic and immunohistochemical evaluation for diagnostic confirmation of presumed inflammatory follicular unit-based disorders that are unusual in presentation or unresponsive to standard therapies. METHODS: A cross-sectional retrospective study of 5 consecutive patients with a histopathologic diagnosis of FMF was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases are presented. RESULTS: We describe 5 patients with clinical and histopathologic presentations of FMF masquerading as hidradenitis suppurativa, furunculosis, or acne vulgaris (age range 34-66 years, 4:1 female to male). Clinical morphologies included open and closed comedones, inflammatory pustules, papules and nodules, follicular papules with keratotic plugging, cysts, and scarring involving the face, trunk, and intertriginous areas. All patients failed to respond to standard therapies, including topical and oral antibiotics, topical and oral retinoids, or topical corticosteroids, before receiving the diagnosis of FMF. Lesional skin biopsies showed a perifollicular CD4-positive T-lymphocytic infiltrate with pilotropism, intrafollicular mucin deposition, foreign-body granulomatous inflammation, acute inflammation, and follicular epithelial necrosis. None had concurrent systemic mycosis fungoides. LIMITATIONS: Small retrospective cohort study. CONCLUSION: We present these cases to expand the clinical and histopathologic spectrum of FMF that may strikingly resemble acneiform disorders and to highlight the importance of diagnostic reconsideration with histopathologic evaluation.

Xanthomatous Dermal Changes in a Patient With Locally Advanced Basal Cell Carcinoma Treated Using Vismodegib.

ABSTRACT: Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer in the United States with more than 2.5 million treated annually. Genetic studies have revealed that approximately 90% of BCCs have a mutation in the hedgehog-signaling pathway. Patients with BCC usually have an excellent prognosis with surgical modalities, however, patients with locally advanced BCC may potentially experience significant cosmetic or functional impairment, with only surgical intervention. Vismodegib is a hedgehog pathway inhibitor that has been successful in treating patients with locally advanced BCC. We report a patient with BCC with a good response to vismodegib and a novel xanthomatous change in the excision specimen.

Evolution of Dupilumab-Associated Cutaneous Atypical Lymphoid Infiltrates.

BACKGROUND: Observations highlighting the "unmasking" of cutaneous T-cell lymphoma after treatment with dupilumab for atopic dermatitis (AD) have been recently reported. However, there remains a paucity of literature describing the evolution of clinical and histopathological features that characterizes this phenomenon. OBJECTIVE: To define the clinical and histopathologic evolution of atypical lymphoid infiltrates after the administration of dupilumab for AD. METHODS: A cross-sectional study of clinical and histopathologic features in 7 consecutive patients with a diagnosis of "atypical lymphoid infiltrate" or mycosis fungoides (MF) on dupilumab for AD was performed. RESULTS: Seven patients with atypical lymphoid infiltrates or MF in evolution after dupilumab therapy (age range 27-74 years) were reviewed. Average duration of AD before MF diagnosis was 5.7 years, and the average duration on dupilumab treatment was 9.8 months. Notable histopathologic features across predupilumab and postdupilumab biopsies included progressive increase in the densities of the atypical lymphoid infiltrates (7/7), presence of atypical epidermotropic lymphocytes (6/7), and papillary dermal fibrosis (6/7). LIMITATIONS: Small retrospective cohort study. CONCLUSION: These cases highlight the transformation of lymphoid infiltrates after dupilumab treatment for AD and emphasize the importance of clinical and histopathologic evaluation before and during treatment with dupilumab for treatment-refractory presumed AD.

Unilateral swelling and hyperpigmented papules.

Lymphangioendothelioma, also known as acquired progressive lymphangioma, is a rare vascular neoplasm of lymphatic origin. Although in light-skinned individuals lesions typically present as erythematous to violaceous papules or plaques, in dark-skinned patients lesions often appear hyperpigmented. Histopathologic distinction of lymphangioendothelioma from early Kaposi sarcoma and angiosarcoma is imperative considering the therapeutic and prognostic implications. Herein, we present a 71-year-old woman with slowly progressive hyperpigmented papules and histopathology demonstrating thin-walled vascular spaces interspersed between collagen bundles, consistent with lymphangioendothelioma. We describe the clinical and histologic findings of this rare entity and highlight histologic mimics that might result in diagnostic delay.