Invasion risk of cutaneous squamous cell carcinoma in situ by histological subtype: a retrospective cohort study.

AIMS: Cutaneous squamous cell carcinoma in situ (SCCis) can be classified histopathologically into four subtypes: full-thickness (FT), hypertrophic actinic keratosis (HAK), Bowenoid, and acantholytic types. 3%-5% of SCCis lesions progress to invasive squamous cell carcinoma (iSCC), however progression risk by subtype has not been assessed. Aim one of this study is to quantitatively assess the risk of iSCC associated with each histological subtype of SCCis. Aim two is to evaluate if the histological grade of iSCC differs among subtypes of the associated SCCis. METHODS: The pathology information system at our institution was queried for cutaneous SCCis cases with and without associated iSCC from 2020 to 2022. The study group consisted of 65 cases of SCCis with associated iSCC and control group 65 randomly selected cases of SCCis without invasion. For each case SCCis subtype was classified as FT, HAK, Bowenoid or acantholytic type. iSCCs were classified as low grade if well to moderately differentiated (LG) and high grade (HG) if moderately to poorly differentiated. RESULTS: iSCC was most often associated with HAK-type SCCis, followed by acantholytic and FT-type SCCis, with Bowenoid type rarely associated with iSCC. 41% (14/34) of iSCCs associated with HAK-type SCCis were HG compared with 84% (21/25) for FT-type SCCis. CONCLUSIONS: iSCC is most often associated with HAK-type SCCis, followed by acantholytic and FT-types, and rarely with Bowenoid type. HG invasive SCC is most often associated with FT-type, and LG with HAK-type SCCis. Stratifying SCCis by subtype can inform clinical management.

Clonal-pattern Seborrheic Keratosis: Risk of Recurrence and Progression to Carcinoma.

Seborrheic keratosis is a benign epidermal tumor. Seborrheic keratosis with clonal pattern (CPSK) displays histologic features distinct from other subtypes of SK (non-CPSK). We sought to quantitatively assess the risk of recurrence and progression to squamous cell carcinoma (SCC), either in situ or invasive, of incompletely excised CPSKs. We studied all 244 cases from 238 patients of "seborrheic keratosis, clonal pattern" diagnosed in our institution over a 10-year period (2008-2018). Demographic, clinical, pathologic, and follow-up data were gleaned from electronic health records. Following glass slide review, CPSK lesions were divided into 2 groups: CPSK with cytologic atypia and CPSK without cytologic atypia. For comparison, 107 non-CPSKs were studied as controls. The minimum follow-up period was 2 years (median=4 y). All lesions were incompletely excised. Eighteen of 244 CPSKs (7.4%) recurred at or adjacent to the site of initial partial removal compared with 1.9% of non-CPSKs. Five of the 18 (28%) recurrent CPSKs recurred as CPSK, 11 (61%) as SCC in situ, and 3 (17%) as invasive SCC. The mean time to recurrence was 3.1 years. Two non-CPSKs recurred as non-CPSKs. Overall CPSKs were more likely to recur than non-CPSKs ( P =0.04). CPSKs with atypia were more likely to recur than CPSKs without atypia ( P =0.03). The upgrade rate to SCC at least in situ of all recurrent CPSK lesions with atypia was 78%. Our results suggest that pathologists should report the presence of clonal pattern when observed in seborrheic keratoses, indicate the presence of atypia, and provide lesional margin assessment.

Dogliotti and Phillips classifications are unsuitable for grading the histopathological findings of exogenous ochronosis.

BACKGROUND: Cutaneous exogenous ochronosis (EO) is frequently graded and staged according to the Dogliotti or Phillips classification system, both in research studies and in clinical practice. There are no data to support the use of these systems in either of these settings. These systems additionally purport that the clinical and histopathological findings of EO are concordant; however, anecdotal evidence suggests otherwise. We aimed to determine the clinical-histopathological concordance rates in EO and to assess the suitability of the Dogliotti and Phillips classification systems for the grading and staging of EO lesions. METHODS: Five cutaneous EO cases diagnosed at our institution were studied. Clinical and histopathological data were obtained by medical record and histopathology slide review. Each case was assigned a clinical and histopathological grade according to both the Dogliotti and Phillips classifications. Clinical-histopathological concordance rates were determined for each classification. RESULTS: Clinical-histopathological concordance was seen in 80% and 60% of EO lesions when graded according to the Dogliotti and Phillips classifications, respectively. CONCLUSIONS: Cutaneous EO lesions do not consistently show clinical-histopathological concordance. Although the Dogliotti and Phillips classifications may have clinical utility, they are not suitable to grade EO histopathologically.

Changing Trends in Dermatopathology Case Complexity: A 9-Year Academic Center Experience.

CONTEXT.­: Pathology case volume and complexity impact clinical service burden, staffing, and reimbursement, particularly in an academic setting. OBJECTIVE.­: To investigate dermatopathology case complexity by using indicators of challenging cases, which require increased clinical service effort. DESIGN.­: A retrospective review was performed of dermatopathology cases during a 9-year period at a tertiary care academic center. A subset of cases was analyzed for which extractable data were available. Cases requiring the following metrics of complexity were identified: rush processing, consensus agreement, performance of immunohistochemistry, use of special histochemical stains, use of immunofluorescence, examination of additional tissue levels, review of a prior case, addition of an explanatory note, presence of multiple specimen parts, and use of intradepartmental consultation. RESULTS.­: A total of 8173 cases were reviewed. During the same 3-month period of the year, there was a statistically significant increase in use of rush processing/interpretation, consensus review, number of cases requiring immunostains, special stains, levels, and an explanatory note, and cases reviewed by other subspecialists in the department from 2010 to 2019. CONCLUSIONS.­: This study shows an increasing trend in dermatopathology case complexity, suggesting that overall clinical service efforts have increased. These findings may inform clinical service staffing and reimbursement.

Intralymphatic histiocytosis in healing cellulitis: Case report and review of the literature.

Intralymphatic histiocytosis (ILH) is a rare skin benign condition observed in a variety of inflammatory settings. It is characterized by the presence of ectatic dermal lymphatic vessels containing aggregates of histiocytes. Associated conditions that have been identified include rheumatoid arthritis, metallic orthopedic implants, inflammatory bowel disease, and malignancies of the breast, skin, and colon. Some cases with no attributable underlying cause have been described. The pathophysiology of ILH is not well understood. It has been proposed that it may represent macrophage migration during immune activation. Herein, we present the first description of ILH observed in the healing phase of cellulitis on the skin of the breast. Awareness of this possibility is important when the diagnosis of intravascular carcinomatosis is being considered.

A pink enlarging plaque on the plantar foot: amelanotic acral lentiginous melanoma.

Acral lentiginous melanomas account for less than 5% of all melanomas, whereas amelanotic melanomas account for around 2-8% of all melanomas. Amelanotic acral lentiginous melanomas are even less common and can often be mistaken for other clinical entities, including pyogenic granulomas, non-melanoma skin cancers, and warts. We describe a man in his 50s with a twenty-year history of a skin-colored plaque on the right plantar foot; after enlargement and failure of wart treatment, a shave biopsy revealed an amelanotic melanoma. A subsequent wide local excision and sentinel lymph node biopsy revealed melanoma in 4 lymph nodes and the patient underwent an abbreviated course of interferon-alpha therapy. The patient remained stable until 2 ? years after diagnosis, at which time he presented with in-transit metastases on the foot and right thigh; he has since been stable on nivolumab. This case represents the challenge of diagnosing amelanotic melanomas on acral surfaces and highlights the importance of considering a skin biopsy for diagnosis of any changing, atypical amelanotic lesions on the feet or hands.

Folliculin mutation-negative trichodiscomas in a patient with multiple endocine neoplasia type I syndrome.

Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma that involves the oral mucosal. The manifestation of lesions within the oral cavity generally correlates with a poor prognosis. Management of MF includes skin directed therapies and localized radiation treatment, with systemic biologic therapies and chemotherapy used for more advanced stages. The clinical and histologic features of MF in a patient with oral disease are reviewed.

Chronic Q-Fever (Coxiella burnetii) Causing Abdominal Aortic Aneurysm and Lumbar Osteomyelitis: A Case Report.

Coxiella burnetii is a rare cause of chronic infection that most frequently presents as endocarditis. We report a case of C burnetii causing an infected abdominal aortic aneurysm with contiguous lumbar osteomyelitis resulting in spinal cord compromise. The diagnosis was established by serologic studies consistent with chronic Q-fever (ratio of C burnetii immunoglobulin [Ig]G phase II titer to IgG phase I titer <1) and was confirmed by positive C burnetii polymerase chain reaction of vertebral tissue in addition to pathology of vertebral bone showing intracellular Gram-negative coccobacillary bacteria. The patient clinically improved after surgical decompression and prolonged treatment with doxycycline and hydroxychloroquine.

Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

BACKGROUND: Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes. METHODS: Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas. RESULTS: The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%. CONCLUSIONS: The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms.

Cutaneous granulomatous eruption and successful response to potent topical steroids in patients undergoing targeted BRAF inhibitor treatment for metastatic melanoma.

IMPORTANCE: Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported. OBSERVATIONS: Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy. CONCLUSIONS AND RELEVANCE: We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management.

Telaprevir-related dermatitis.

OBJECTIVE: To evaluate the incidence, type, and severity of telaprevir-associated skin reactions. DESIGN: Three dermatologists assessed available information including photographs, biopsy results, and clinical summaries of all cases with skin eruptions reported as moderate or severe during the telaprevir clinical development program. For cases from placebo-controlled trials, they were masked to exposure. SETTINGS: Phase 1 to 3 studies of telaprevir combination therapy for hepatitis C. PATIENTS: All patients with skin eruptions enrolled in telaprevir clinical trials prior to 2011 MAIN OUTCOME MEASURES: Incidence, diagnosis, morphologic features, extent, and severity of skin eruption. RESULTS: Skin eruptions were more frequent in patients who received telaprevir as part of hepatitis C treatment compared with pegylated interferon (peginterferon) and ribavirin alone (56% vs 34% overall; 3.7% vs 0.4% severe). Occurring at any time during the 12 weeks of telaprevir combination regimen, in more than 90% of cases, this eruption is pruritic eczematous dermatitis. None of the clinical or genetic factors examined were substantial risk factors for dermatitis. Three cases of Stevens-Johnson Syndrome (SJS), and 11 cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were suspected, with 2 SJS and 3 DRESS cases considered likely. CONCLUSIONS: Telaprevir-related dermatitis occurs in a majority of telaprevir-treated patients. It is an eczematous dermatitis that differs in timing and appearance from the eruptions usually associated with drug reactions. The strong signal for an increased risk of DRESS or SJS requires particular vigilance in telaprevir-treated patients.

A randomized, controlled trial of four ablative fractionated lasers for photoaging: a quadrant study.

BACKGROUND: Fractionated technology has revolutionized laser therapy. With the success of initial devices, several fractionated lasers have appeared on the market. Claims of superiority have made device choice difficult for physicians and patients. MATERIALS AND METHODS: Twelve subjects were treated with fractionated ablative lasers (10,600-nm carbon dioxide and 2790-nm yttrium scandium gallium garnet) in this institutional review board-approved trial. Each face was divided into four quadrants, and each quadrant was randomly treated using one of four lasers. Clinical experience was used to optimize settings. Two patients submitted biopsies from each quadrant immediately after treatment. Patients and blinded investigators assessed pain during treatment and post-treatment improvement in photoaging (measured by rhytides, lentigines, texture, and pore size) using a five-point scale. RESULTS: All devices resulted in statistical improvement in photoaging in all patients, but no device was statistically significantly superior. No statistically significant difference was found in pain scores. All patients reported satisfaction 1 month after treatment. Three patients experienced adverse reactions. Histologically, there were no statistically significant differences between devices. CONCLUSIONS: Fractionated ablative lasers reliably result in improvement in photoaging. Despite marketing claims, no statistically significant differences were found in outcomes, pain during treatment, or histologic findings. Even with experienced users, significant adverse reactions are possible.