Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

False-Negative Rate of Direct Immunofluorescence on Lower Extremities in Bullous Pemphigoid.

ABSTRACT: Bullous pemphigoid (BP) is the most common autoimmune blistering disorder of the skin. It is typified by tense blisters with a subepidermal split and mixed dermal inflammatory infiltrate on histology. Biopsy of the perilesional skin for direct immunofluorescence (DIF) has become the gold standard in the diagnosis of BP. Currently there is a pervasive clinical opinion that the lower extremity is a site with a high false-negative rate (FNR) for DIF in the diagnosis of BP. This notion is primarily based on 2 early studies from the 1980s without more recent confirmatory studies. To readdress this question regarding the lower extremities, a retrospective study from 2012 to 2018 was performed in our institution that evaluated the FNR of DIF by an anatomical site in the diagnosis of BP. Cases of BP were identified using standard criteria (clinical and histological data reviewed in cases with negative DIF), and overall, 79 patients were included in the study. A total of 4 false-negative DIF biopsies were verified. Two negative DIF were from the lower extremity yielding a FNR of 10% compared with 4% on the trunk and 3% from the upper extremity, with no statistically significant difference by anatomical sites. Our study fails to demonstrate a high FNR of DIF from the lower extremity in the diagnosis of BP.

Syringotropic Mycosis Fungoides: A Variant of Folliculotropic Mycosis Fungoides or a Distinct Entity?

Syringotropic mycosis fungoides (MF) is classified under folliculotropic MF. Although there is significant overlap between the 2, this study demonstrates that folliculotropism is frequently present in syringotropic MF, and when not present, the specimen did not include a follicle to examine. In addition, few of the pathology reports mentioned folliculotropism or syringotropism, although this is an important prognostic feature.

"Low-Fat" Pseudoangiomatous Spindle Cell Lipoma: A Rare Variant With Loss of 13q14 Region.

Spindle cell and pleomorphic lipoma constitute a spectrum of lipomatous lesions with characteristic clinical, morphologic, immunohistochemical, and molecular features. Multiple variants have been previously described including vascular, fibrous, plexiform, and those with significantly less fat termed "low-fat" and "fat-free" by Folpe. Cytogenetically, spindle cell lipomas frequently display monoallelic loss of 13q14 region, an abnormality also found in cellular angiofibroma and mammary-type myofibroblastoma. Pseudoangiomatous spindle cell lipoma, originally described by Fletcher et al in 1994, is a rare variant within the spindle cell/pleomorphic lipoma spectrum, with less than 20 published cases. It consists of an admixture of spindle cells, "ropey" collagen, variable amounts of mature fat, and irregular, branching slit-like vascular spaces. The authors present a case of a 1-cm subcutaneous lesion excised from the neck of a 70-year-old man with classic histologic and immunohistochemical features of "low-fat" pseudoangiomatous spindle cell lipoma. Fluorescence in situ hybridization demonstrated a loss of 13q14 region, a characteristic presumed cytogenetic finding of spindle cell lipoma, which has been previously unconfirmed in this variant.

Keratoacanthoma clinical behavior: a systematic review.

As of 2013, keratoacanthomas (KAs) have not been decided on as either a benign or a malignant entity. Originally considered benign epidermal growths, the assertion by Hodak, Jones, and Ackerman that these lesions are truly "an expression of squamous cell carcinoma" (SCC) fueled the controversy and placed some of the biggest names in the field on opposite sides of the issue. Without a clear understanding of the etiology of KAs and without stringent diagnostic criteria, the literature in regard to KA contains scant reports of their "metastatic potential." Four hundred forty-five cases of KA with reported follow-up and outcomes were reviewed from 113 published articles. In our data set, none of these cases resulted in death or distant metastases. When compared with 429 cases of SCC of the skin, with 61 cases of metastases and 24 deaths as a direct result of SCC, the biologic behavior of the 2 entities is distinct and evident. KAs are benign epidermal growths and not a malignant variant of SCC.

Histologic features of scalp melanocytic nevi.

BACKGROUND: The scalp has been proposed as an anatomic site that harbors melanocytic nevi with distinctive histologic attributes, so-called "special-site" nevi, similar to nevi on the breast and genitalia. However, detailed studies are lacking. OBJECTIVE: We sought to better delineate the features of scalp melanocytic nevi, particularly lesions that may qualify as special-site nevi. METHODS: The histologic features of 365 total melanocytic nevi of the scalp were studied from 322 patients over a consecutive period of 18 months from July 2007 through January 2009. RESULTS: A total of 56 nevi with characteristic features were identified. The most common features were: (1) random melanocytes containing large nuclei (92.9%) and abundant pale cytoplasm with dusty melanin granules (96.4%); (2) large nests (76.8%) situated along the sides of rete and between rete ridges (85.7%); (3) nests of poorly cohesive melanocytes (82.1%); (4) overlap features with Clark nevi (75.0%); and (5) overlap features with superficial congenital nevi (50.0%). Pagetoid spread (14.3%), asymmetry (23.2%), and poor lateral demarcation (16.1%) were less common. These 56 lesions predominated in the first 2 decades of life and were not observed after age 35 years. LIMITATIONS: Lack of long-term clinical follow-up of patients is a limitation; however, no recurrences or malignancies from these patients' scalps were submitted in the time period (≥ 3 years) since the initial biopsies. CONCLUSION: A special site scalp nevus is recognizable amongst scalp melanocytic nevi, and this lesion is more common in younger patients. Familiarization of its features should assist in the diagnosis and management of scalp melanocytic lesions.

Multiple myeloma diagnosed secondary to analysis of a lytic bone lesion encountered during Mohs micrographic surgery.

An 89-year-old man underwent Mohs micrographic surgery for treatment of a squamous cell carcinoma of the scalp. A lytic bone lesion was found that led to the diagnosis of multiple myeloma.

Molecular biology of melanoma.

Dermatologists and dermatopathologists face the difficulties of accurately diagnosing and treating atypical melanocytic lesions and melanomas. Despite huge advances in medicine, our management of melanoma has not significantly changed in many years. The biggest gains made recently have been in the identification of common mutations in melanoma and the use of these mutations to aid in the diagnosis and treatment of melanoma. To understand these gains one must first be familiar with the regulatory pathways of melanoma and the most common mutations found there. This article will review the function and significance of the most studied mutations in melanoma and briefly discuss new and planned treatment options.

Giant fibrous hamartoma of infancy: a report of two cases and review of the literature.

We present two unique cases of fibrous hamartoma of infancy defined by giant-sized and/or multicentric cutaneous and subcuticular lesions--features not, to our knowledge, reported to coexist. We review the nature of such tumors and examine the clinical implications of tumor size and multicentricity on risk for recurrence and likelihood of visceral involvement.

Patient safety: Part I. Patient safety and the dermatologist.

UNLABELLED: Congress is grappling with ways to fund health care in the future. Much of the focus rests on paying physicians for their patients' outcomes, rather than the current system of payment for services provided during each visit. The years ahead will be years of change for American health care, with an increasing emphasis on the comparison of patient outcomes and measures of quality. Patient safety initiatives will be an integral part of the overall strategy to improve American health care. Part one of this two-part series on patient safety examines what we know about patient safety in dermatology, including data from medicolegal claims and published data on patient safety in the setting of office-based surgery. The article also focuses on how medical societies, payers, the US government, and the Board of Medical Specialties are responding to calls for accountability and improvements in patient safety. LEARNING OBJECTIVES: After completing this learning activity, participants should be able to identify risks to patient safety based on an understanding of the major causes of legal claims against dermatologists, use published patient safety data to improve the practice of office surgery, and be able to improve patient safety through an understanding of requirements for maintenance of certification.

Lupus-like histopathology in bloom syndrome: reexamining the clinical and histologic implications of photosensitivity.

Bloom syndrome is a rare genodermatosis of autosomal recessive inheritance. Although lupus-like skin lesions characterize this disorder, mechanisms of photosensitivity are poorly understood. In this case presentation, the authors report a patient with Bloom syndrome whose lupus-like facial rash revealed striking histopathologic similarities to cutaneous lupus erythematosus.

The role of observation in the management of atypical nevi.

OBJECTIVE: The definition and management of the atypical nevus remains a controversial issue. Some believe that atypical nevi are common variants of benign melanocytic nevi while others believe they are lesions intermediate between benign melanocytic nevi and melanoma. Therefore, the question of whether or not partially removed atypical nevi should be re-excised with clear margins in order to prevent their evolution into melanoma remains unanswered. Although studies have shown that most atypical nevi will never progress into melanoma, re-excision, when biopsy margins are positive, is commonly practiced. We argue that re-excision in such cases is not necessary. METHODS: Our cohort study includes 55 previously biopsied atypical nevi that were not re-excised and which were followed for at least 5 years with a mean follow up time of 6.12 years. RESULTS: The experimental group included 26 atypical nevi whose biopsy revealed at least one involved margin. The control group included 29 atypical nevi whose biopsy revealed clear margins. No melanomas were observed to arise in association with a pre-existing atypical nevus in either the experimental or control group during the follow-up period. CONCLUSIONS: The results of our study support observation as a safe alternative to re-excision for incompletely removed atypical nevi. A large prospective study with longer follow up would be necessary to better answer the question of how often atypical nevi evolve into melanoma and over what time period this occurs.

Unilateral eosinophilic fasciitis: an under-recognized subtype?

Symmetric skin thickening of the limbs with deep fascial inflammation is the hallmark of eosinophilic fasciitis. We describe a woman who presented with unilateral progressive skin thickening. Examination of a full thickness skin biopsy revealed an inflammatory process and fascial changes consistent with eosinophilic fasciitis. In contrast to other scleroderma mimics, eosinophilic fasciitis generally responds rapidly to glucocorticoid therapy. It is possible that unilateral eosinophilic fasciitis is under-recognized and can easily be misdiagnosed as another scleroderma variant if a full thickness biopsy is not reviewed by a dermatopathologist. Recognition of this subtype of eosinophilic fasciitis is important given the profound differences in prognosis of eosinophilic fasciitis and other scleroderma variants.

Chemokine receptor expression in non-melanoma skin cancer.

BACKGROUND: Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro-inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (alpha) chemokine receptor (CXCR)4 and CC (beta) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non-melanoma skin cancer have yet to be elucidated. METHODS: The expression patterns of CCR6, CCR7 and CXCR4 were determined using an immunohistochemical approach on formalin-fixed, paraffin-embedded normal, pre-cancerous actinic (solar) keratosis, squamous cell carcinoma and basal cell carcinoma tissues. RESULTS: Analysis of chemokine receptor expression showed downregulation of CCR6 and upregulation of CCR7 and CXCR4 in potentially metastatic non-melanoma skin cancer, invasive squamous cell carcinoma, but this pattern did not exist in non-melanoma skin cancer with no metastatic potential, basal cell carcinoma; or actinic keratosis, when compared with normal skin. CONCLUSIONS: Chemokine receptor expression may influence the biological behavior of non-melanoma skin cancer. The exact mechanism by which this occurs requires further study.

Papulonecrotic eruption in a 44-year-old-man.

A patient is described who presented with the acute onset of widely distributed necrotic papules mimicking pityriasis lichenoides et varioliformis acuta. A skin biopsy revealed granulomatous inflammation and spirochetes were demonstrated. Serologic testing confirmed infection with the Treponema pallidum. Syphilis is still a great imitator and its persistence as an infectious disease is reviewed.

Localized cutaneous argyria from an acupuncture needle clinically concerning for metastatic melanoma.

Localized cutaneous argyria presenting as an asymptomatic blue-gray macule has been rarely reported from diverse etiologies including occupational exposures, topical medications, alternative medical therapies, body jewelry, and dental procedures (amalgam tattoos). The lesions often are clinically indistinguishable from blue nevi and malignant melanoma. We present a case of localized cutaneous argyria from an acupuncture needle in a patient with a history of malignant melanoma. Fine granules of nonbleachable dark particles coating collagen and elastin fibers, altered yellow-brown collagen bundles similar to ochronosis, and involvement of eccrine structures were histologically consistent with the pseudo-ochronosis pattern of localized cutaneous argyria, demonstrating that clinicopathologic correlation is of crucial importance.