Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report.

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis. Case presentation: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms. Discussion: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy. Conclusion: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.

Merkel Cell Hyperplasia Versus Intraepidermal Merkel Cell Carcinoma: A Comparative Study of 2 Cases.

ABSTRACT: Intraepidermal Merkel cell hyperplasia and Merkel cell carcinoma represent 2 histologically similar-appearing diagnoses with significant differences regarding prognosis and management. We present 1 case of each diagnosis to highlight characteristic histopathologic and immunohistochemical features. Our case of Merkel cell hyperplasia was identified by its small intraepidermal nest of monomorphic cells without atypia or mitoses, which demonstrated cytoplasmic, rather than perinuclear dot, patterning on CK20 staining. This can be contrasted with our case of intraepidermal Merkel cell carcinoma, which, despite a lack of dermal extension, demonstrated large nests of pleomorphic cells with frequent mitoses and apoptoses. The diagnosis was further confirmed by immunohistochemistry because CK20 staining showed classic perinuclear dot patterning. By presenting both diagnoses in parallel, this comparison aims to underscore crucial histopathologic and immunohistochemical similarities and differences.

Application of the current diagnostic algorithm for early mycosis fungoides to a single center cohort: Identification of challenges and suggestions for modification.

BACKGROUND: Diagnosing early-stage mycosis fungoides (MF) remains a significant challenge. The International Society for Cutaneous Lymphomas (ISCL) proposed an algorithm for diagnosing early MF incorporating clinical and histopathologic characteristics, as well as immunohistochemistry and molecular studies. Here we aim to examine the diagnostic utility of the ISCL algorithm. METHODS: In this single-center retrospective review, the ISCL algorithm was applied to 28 patients diagnosed with early-stage MF. Immunohistochemistry and molecular studies were not performed for all patients, so a subgroup analysis was conducted including 18 patients in whom both studies had been performed. We calculated the diagnostic sensitivity of the algorithm. Subsequently, we examined how modifying the algorithm's histopathologic criterion from epidermotropism without spongiosis to epidermotropism influenced its sensitivity. RESULTS: Forty-three percent (12/28) of the cohort and 50% (9/18) of the subgroup met the algorithm's diagnostic threshold. When the algorithm was modified, 71% of the cohort and 89% of the subgroup met the algorithm's threshold. CONCLUSION: While the ISCL algorithm is useful in diagnosing early-stage MF, its sensitivity remains suboptimal. Further refinement of the algorithm to capture spongiotic subtypes of MF may improve its diagnostic value.

Disease characteristics, prognosis, and response to therapy in patients with large-cell transformed mycosis fungoides: A single-center retrospective study.

BACKGROUND: Mycosis fungoides with large-cell transformation (MF-LCT) is associated with an aggressive clinical course, yet data comparing treatment outcomes in MF-LCT are sparse. OBJECTIVE: To compare treatment outcomes and to determine disease prevalence and characteristics associated with survival in MF-LCT. METHODS: A retrospective review was conducted of mycosis fungoides patients from 2012 to 2020 treated at Thomas Jefferson University. Patients with histopathologic diagnosis of MF-LCT were included. Treatment outcomes were assessed by mean changes in the modified Severity Weighted Assessment Tool (mSWAT) and stage. RESULTS: Of 171 patients with mycosis fungoides, 23 (13.4%) had histologic diagnosis of MF-LCT. The overall 5-year survival rate for MF-LCT was 74% and was not significantly associated with sex, age, or initial stage at the time of MF-LCT diagnosis. Brentuximab vedotin showed the greatest mean decrease in mSWAT (-20.53) and stage progression (change in Δ stage: -0.4) in MF-LCT compared to oral bexarotene (ΔmSWAT: +4.51; Δstage: +0.27), skin-directed therapy (ΔmSWAT: -5.93; Δstage: -0.08), and chemotherapy (ΔmSWAT: +4.97; Δstage: +0.85). LIMITATIONS: Single-center retrospective design, and patients often on multiple treatment modalities. CONCLUSIONS: We report superior treatment outcomes for brentuximab vedotin compared to oral bexarotene, skin-directed therapy, and chemotherapy in MF-LCT in both early and advanced disease.

High-Dose-Rate Brachytherapy for the Treatment of Basal and Squamous Cell Carcinomas on Sensitive Areas of the Face: A Report of Clinical Outcomes and Acute and Subacute Toxicities.

PURPOSE: Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face. METHODS AND MATERIALS: Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos were reviewed at multiple time points: start of treatment, end of treatment, short-term (2 week) follow-up, 3-month follow-up, and if needed at 6 months. Radiation toxicity was graded using the Radiation Therapy Oncology Grading (RTOG) acute toxicity scale. Median (range) toxicity grades at follow-up intervals were calculated. Clinical outcomes including local recurrence were evaluated for all patients. RESULTS: The study included 19 patients and 20 KCs. The median radiation dose was 42 Gy (39-42 Gy) over 6 fractions. The median toxicity at completion of treatment was RTOG grade 2 (85% of patients). At short-term follow-up, 50% of patients (n = 10) improved to RTOG grade 1 (0-2). At 3 months, 70% of patients (n = 14) had RTOG grade 0, and by 6 months, 100% of patients (n = 18) had RTOG grade 0. No RTOG grade 3 or higher skin toxicity was observed. With a median follow-up of 7.2 months (range, 1.3-54.4 months), the local recurrence-free survival was 95%. CONCLUSIONS: We demonstrate that HDR-BT can be used as definitive treatment of KCs of the face with excellent cosmetic outcomes and local control. Acute and subacute skin toxicities were most commonly RTOG grade 2 or less with resolution of patient's skin toxicity by 3 months.

Reactive granulomatous dermatitis associated with ovarian cancer and a review of its role as a harbinger for malignancy.

Reactive granulomatous dermatitis (RGD) is a rare dermatosis with a variety of cutaneous manifestations unified by a dermal granulomatous infiltrate on histology. Rheumatoid arthritis and autoimmune disease are classic associations, but an increasing number of cases have been attributed to covert malignancy. Only 41 cases of paraneoplastic RGD have been documented to our knowledge and we present an additional case that manifested eight months prior to the diagnosis of ovarian cancer and clinically mimicked morphea. Histopathologic examination identifying palisaded CD68+ cells and collagen degeneration are helpful in diagnosing this entity which may mimic a host of other cutaneous processes, including metastatic disease. Cancer-directed therapies have been successful in clearing paraneoplastic RGD with or without the addition of corticosteroids, as RGD severity may be driven by the underlying malignancy. This case highlights the importance of utilizing histopathology to confirm the diagnosis given its nonspecific clinical findings, as well as the importance of considering malignancy and metastatic disease in patients diagnosed with RGD regardless of their cancer history.

Response to topical corticosteroid monotherapy in mycosis fungoides.

BACKGROUND: Topical corticosteroids alone or in combination with other therapies are widely used to treat mycosis fungoides (MF), but data on response rates to their use as monotherapy in MF are limited. OBJECTIVE: To evaluate the efficacy of topical corticosteroid monotherapy in MF; compare sex, age, stage distributions, and histopathologic features between responders and nonresponders. METHODS: A retrospective cross-sectional review of patients with MF from 2013 to 2019 treated at Thomas Jefferson University was conducted. Patients with biopsy-proven MF, all stages, who received topical corticosteroid monotherapy were included. Response rates were determined by percent change in body surface area (BSA) involvement and modified Severity-Weighted Assessment Tool (mSWAT). RESULTS: Of the 163 patients with MF in our database, 23% (37/163) initially received topical steroid monotherapy. Of these, 73% (27/37) improved, with an average 65% decrease in BSA (67% in mSWAT); 27% (10/37) did not respond/progressed, with an average 51.6% increase in BSA (57% in mSWAT); and 33% (12/37) had a complete response (BSA, 0%) with prolonged topical steroid use. Early-stage MF and female sex were more represented in responders. LIMITATIONS: Single-center retrospective design. CONCLUSIONS: Topical steroid monotherapy in early-stage MF can produce measurable improvements in BSA and mSWAT scores and achieve complete remission in a limited subset of patients.

Toxic erythema of chemotherapy secondary to gemcitabine and paclitaxel.

Toxic erythema of chemotherapy (TEC) is an infrequently reported cutaneous condition, with diagnosis predominately based on clinical presentation, histologic findings, and known reported associations. Therefore, it is important to both recognize common presentations of TEC and be mindful of chemotherapeutic agents associated with this cutaneous side effect to prevent misdiagnosis and prolonged time to treatment. Herein, we present a patient with TEC occurring in intertriginous skin (malignant intertrigo) with classic clinical and histologic findings. In our patient this was associated with a combination neoadjuvant gemcitabine and paclitaxel therapy, a relationship that, to our knowledge, has yet to be reported in the literature.

Botulinum toxin: Pharmacology and injectable administration for the treatment of primary hyperhidrosis.

Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis.

Impaired wound healing secondary to bevacizumab.

Bevacizumab is a monoclonal antibody that exerts its antitumor activity by inhibiting vascular endothelial growth factor. Consequently, it suppresses endothelial cell proliferation, vascular permeability, and angiogenesis. This inhibitory effect contributes to tumour size reduction but causes wound-healing delay, specifically during the proliferative phase, in patients receiving bevacizumab. Although surgical wound-healing complications (WHC) associated with bevacizumab have been extensively reported, there is limited literature on peripheral WHC. More importantly, the histopathology of bevacizumab-associated WHC has not been described. We present the histopathology findings of a non-healing ulcer in a patient receiving bevacizumab, providing insight into the possible aetiology of this drug's adverse reaction. Furthermore, our patient's positive response to hyperbaric oxygen suggests its possible use for treatment of bevacizumab-associated non-healing wounds.

The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Therapeutic options.

Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality of life. A variety of treatment modalities currently exist to manage HH. Initial treatment includes lifestyle and behavioral recommendations. Antiperspirants are regarded as the first-line therapy for primary focal HH and can provide significant benefit. Iontophoresis is the primary remedy for palmar and plantar HH. Botulinum toxin injections are administered at the dermal-subcutaneous junction and serve as a safe and effective treatment option for focal HH. Oral systemic agents are reserved for treatment-resistant cases or for generalized HH. Energy-delivering devices such as lasers, ultrasound technology, microwave thermolysis, and fractional microneedle radiofrequency may also be utilized to reduce focal sweating. Surgery may be considered when more conservative treatments have failed. Local surgical techniques, particularly for axillary HH, include excision, curettage, liposuction, or a combination of these techniques. Sympathectomy is the treatment of last resort when conservative treatments are unsuccessful or intolerable, and after accepting secondary compensatory HH as a potential complication. A review of treatment modalities for HH and a sequenced approach are presented.

The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Etiology and clinical work-up.

Hyperhidrosis (HH) is a dermatologic disorder defined by sweat production exceeding thermoregulatory needs. Clinically, HH is diagnosed when excess sweating creates significant emotional, physical, or social discomfort, causing a negative impact on the patient's quality of life. Existing data imply that this condition may affect at least 4.8% of the US population. The etiology of HH may stem from a complex autonomic nervous system dysfunction, resulting in neurogenic overactivity of otherwise normal eccrine sweat glands. Alternatively, HH may be a result of aberrant central control of emotions. This condition is categorized as primary or secondary HH. Approximately 93% of patients with HH have primary HH, of whom >90% have a typical focal and bilateral distribution affecting the axillae, palms, soles, and craniofacial areas. Secondary HH presents in a more generalized and asymmetric distribution and is generated by various underlying diseases or medications. Secondary causes of HH need to be excluded before diagnosing primary HH.

Multiple Eruptive Eccrine Poromas Associated with Chemotherapy and Autologous Bone Marrow Transplantation.

Eccrine poroma is a benign adnexal tumor that originates from the uppermost portion of the intraepidermal eccrine duct. It usually presents as a solitary tumor. Histopathology shows a monomorphic proliferation of cuboidal cells, which radially extend from the basal layer to the dermis. Here, we present a rare multilesional eruption of eccrine poroma after chemotherapy and bone marrow stem cell transplantation for acute promyelocytic leukemia along with a description of clinical, pathological, and dermoscopic findings.

Questioning the specificity and sensitivity of ELISA for bullous pemphigoid diagnosis.

The reported sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) for bullous pemphigoid (BP) diagnosis is approximately 87% and 98%, respectively. These statistics suggest that ELISA is a reliable diagnostic test; therefore, the use of ELISA for BP diagnosis has increased. We report the case of a man who was diagnosed with BP and was treated for 3 years based on a positive ELISA for IgG against BP180. After reevaluation, his revised diagnosis was not consistent with BP based on clinical presentation, histopathology, and direct immunofluorescence (DIF). Reviewing reports of ELISA for BP diagnosis in the literature revealed several issues including dissimilar diagnostic procedures and patient populations, multiple reports of positive ELISA in patients without BP, and lack of explanation for these false-positives. This case report and review of the literature is a cautionary tale regarding the use of ELISA as an independently reliable test for BP diagnosis.

A Souvenir From France: Acrodermatitis Chronica Atrophicans Presenting in the United States.

A 70-year-old man was referred by his rheumatologist to our dermatology clinic for evaluation of dermatitis on his right arm that appeared 3 months earlier. The skin lesion was asymptomatic and the patient denied current systemic symptoms, including fever, chills, and joint pain; however, 10 months prior to this presentation he experienced arthritis in the left knee. At that time, Borrelia serology revealed positive IgG (6.07; <0.8 negative, 0.8 to 0.99 borderline, ≥1 positive) and negative IgM titers. The patient had not received treatment for Lyme disease in the past. He was referred to rheumatology for evaluation of possible Lyme disease but did not follow up until 10 months later. The arthritis has since resolved. He travels frequently to France and recalls multiple tick bites during these trips.

A recurrent melanocytic nevus phenomenon in the setting of Hailey-Hailey disease.

Atypical acquired melanocytic nevi in patients with epidermolysis bullosa (EB) have been referred to as EB nevi and are considered to be a type of recurrent nevus with atypical but distinctive histopathologic findings. Herein, we describe an atypical nevus in a patient with Hailey-Hailey disease with different histopathologic findings from EB nevi because of presumably different pathogenesis. It is important to be aware that the recurrent nevi phenomenon can be seen in acantholytic conditions as well as blistering disorders, given these lesions may clinically resemble melanoma.