Amicrobial pustulosis of the folds: A case report of a rare variant of neutrophilic dermatosis associated with systemic lupus erythematosus.

Amicrobial pustulosis of the folds (APF) is a rare neutrophilic dermatosis found in association with autoimmune diseases. We present a 49-year-old woman with a history of systemic lupus erythematosus and a recurrent pustular eruption in the cutaneous folds. Histologic examination revealed spongiform pustulosis and dermal neutrophilic infiltrate. The Gram and periodic acid-Schiff stains were negative for bacteria and fungi. A diagnosis of amicrobial pustulosis of the folds was given. While there is no standard treatment, our patient's symptoms resolved following an oral prednisone taper and have not recurred since starting colchicine. The presence of pustules and erosive plaques in skin folds in young women with autoimmune conditions should raise suspicion for APF. The combination of localized neutrophilic spongiosis with intraepidermal or subcorneal pustules in conjunction with dermal changes of a neutrophilic dermatosis is a helpful clue to the diagnosis. If the patient does not already have a diagnosis of an underlying autoimmune condition, a presentation of APF should prompt further screening consisting of a relevant review of symptoms and appropriate assessment for autoimmune antibodies, since APF may precede the diagnosis of autoimmune disorders.

Neutrophilic fixed drug eruption, a histopathologic variant or an expected finding?-A report of two cases and review of the literature.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by recurrent circumscribed lesions at the same location upon re-exposure to the culprit medication, resulting in distinct postinflammatory hyperpigmentation. Histopathologically, FDE demonstrates a predominantly lymphocytic interface or lichenoid infiltrate with basal cell vacuolar changes and keratinocyte dyskeratosis/apoptosis. The term "neutrophilic fixed drug eruption" has been used to describe cases in which the inflammatory infiltrate is predominantly neutrophilic. The infiltrate can extend deeper in the dermis, potentially mimicking a neutrophilic dermatosis such as Sweet syndrome. We present two cases and review the literature to discuss the possibility that a neutrophilic inflammatory infiltrate may be an expected finding in FDE, rather than a histopathologic variant.

Reactive infectious mucocutaneous eruption due to COVID-19 with erythema-multiforme-like lesions and myeloid cells.

Reactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16-year-old male with COVID-19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non-segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID-19-related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.

Wells Syndrome-Like Histologic Pattern Caused by a Permanent Tattoo.

ABSTRACT: Tattoo reactions have become more common as tattoos gain visibility and popularity worldwide. A variety of inflammatory patterns have been described in association with tattoos- more commonly fibrosing, granulomatous, lichenoid, pseudolymphomatous, and spongiotic patterns. To date, there has been one case report of a Wells syndrome-like inflammatory pattern associated with a temporary Henna tattoo. Here we present the first case of a permanent tattoo with resulting flame figures, histologically resembling Wells syndrome. We believe this uncommon histologic pattern might be of interest for pathologists to be aware of.

An Immune Suppression-associated EBV-positive Anaplastic Large Cell Lymphoma With a BRAF V600E Mutation.

Iatrogenic lymphoproliferative disorders have been described in patients receiving immunosuppressive/immunomodulatory agents outside the transplantation setting. Novel biological agents such as TNF-α blockers and JAK-inhibitors have also proven to be effective in many disorders including rheumatoid arthritis, inflammatory bowel disease (ulcerative colitis and Crohn disease), psoriasis, and others. A significant dilemma exists in those lymphoproliferative disorders associated with immunosuppressants and rheumatologic conditions, that relies on whether the association of the process is with the medication or the underlying autoimmune condition. In the current case report, we describe an extraordinary case of Epstein-Barr virus-positive anaplastic large cell lymphoma, in association with rheumatoid arthritis and the use of JAK-inhibitors. Comprehensive molecular testing (fluorescence in situ hybridization, OncoScan microarray, pyrosequencing) was done comparing sequential biopsies in this patient from skin and lung, which revealed a driving mutation in the BRAF V600E gene, a crucial finding, given the potential use of targeted therapy in this pathway.

Lymphocytes in Sweet syndrome: A potential diagnostic pitfall.

BACKGROUND: Patients with Sweet syndrome (SS) have acute onset of cutaneous lesions with characteristic histopathology (dense and diffuse neutrophilic infiltrate, dermal edema, leukocytoclasis and no vasculitis) accompanied by systemic symptoms. Sometimes, only skin lesions with classic histopathologic features are seen. Although SS is considered to be a "neutrophilic dermatosis," lymphocytes are also seen on histological examination. METHODS: We evaluated the cellular infiltrate in 9 biopsies from SS lesions with routine staining and immunohistochemistry. RESULTS: Lymphocytes were present in all biopsies in variable amounts, often exceeding the number of intact neutrophils. Prominent fragmentation of neutrophils rendered some biopsies "lymphocyte-rich" on routine histologic evaluation. Myeloperoxidase was helpful in highlighting the inconspicuous neutrophilic fragments in these cases. Lymphocytes were highlighted with immunohistochemistry, and had a CD3+, CD4+, CD20(-) immunophenotype, with rare CD8+ lymphocytes. CONCLUSION: Awareness of the lymphocytic component of SS is important to avoid diagnostic errors, especially in subcutaneous lesions of SS, in which the lymphocytic infiltrate predominates in the upper parts of the dermis, while the typical neutrophilic infiltrate may be seen only in the deeper dermis and subcutis. The lymphocytic component may potentially help to differentiate lesions of SS from neutrophilic urticarial dermatosis, which has not been reported to contain a significant lymphocytic population.

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αß T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αß/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

Pseudo-Bullous Dermatosis Induced by Topical Anesthetic Agent-Clues to This Localized Toxic Reaction.

Eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA AstraZeneca, DE) is a widely used topical anesthetic cream for preprocedural cutaneous analgesia. In addition to potential clinical cutaneous and systemic adverse effects, EMLA may also induce microscopic changes detectable by light and electron microscopy leading to difficulty in accurate diagnosis. We report the case of a biopsy demonstrating EMLA-induced histopathologic changes. The biopsy was taken from the back of a 5-month-old infant and submitted to rule out psoriasis. Hematoxylin and eosin (H&E) staining of the biopsy demonstrated spongiosis and a noninflammatory subepidermal bulla, raising the histopathologic possibility of epidermolysis bullosa. Further investigation confirmed that EMLA was applied under occlusion before biopsy. A second biopsy without topical anesthetic did not demonstrate a bulla and supported the clinical diagnosis of psoriasiform dermatitis. Our case highlights the importance of awareness of EMLA-induced histopathologic changes to avoid potential misdiagnosis. The histopathologic findings of this case in conjunction with other previously reported cases of EMLA-induced bullae were analyzed. Vacuolization of the basal and suprabasilar layer, pallor and swelling of upper layer epidermal keratinocytes, a pauci-inflammatory cleavage beneath or within the basal layer, basophilic granular karyorrhectic debris in the subepidermal cleft, and congestion of papillary dermal vessels characterized the biopsy findings of this localized adverse reaction.

Linear Sclerodermoid Lupus Erythematosus Profundus in a Child.

Lupus erythematosus panniculitis, also known as lupus profundus, is a variant in the clinicopathological spectrum of lupus erythematosus (LE) affecting about 2%-3% of LE patients. A linear configuration of LE panniculitis has been reported rarely with rare reports describing the coexistence of different forms of cutaneous LE and localized morphea. In this study, the authors present a 9-year-old girl with linear arrangement of subcutaneous nodules on her left forearm. Microscopic findings from 2 biopsies included lymphocytes at the dermoepidermal junction with mild interface dermatitis, a dense lymphocytic infiltrate that was concentrated around adnexae and subcutaneous fat in concert with thickened collagen bundles and mild widening of fibrous septae surrounding fat lobules. Although the clinical differential diagnosis included panniculitis or a sporotrichoid infection, 1 biopsy showed a dense lymphocytic infiltrate histologically bordered on that of cutaneous lymphoid hyperplasia or a late stage of Lyme disease, and a second also demonstrated more prominent sclerodermoid collagen bundles rendering the diagnosis of linear sclerodermoid LE profundus.

Cystic acantholytic dyskeratosis of the vulva: An unusual presentation of a follicular adnexal neoplasm.

Acantholytic dyskeratosis (AD) is a histologic pattern seen in Darier's disease or dyskeratosis follicularis, warty dyskeratoma, and transient AD. This pattern is characterized by suprabasilar clefting, acantholysis, and formation of corps ronds and grains. We present a case of AD that is unique based on its genital location and cystic architecture. A 53-year-old woman presented with an otherwise asymptomatic cyst on her left vulva of uncertain duration. On microscopic examination, there were fragments of cystic epithelium with areas of hypergranulosis, acantholysis, corps ronds, and corps grains formation. These features are felt by the authors to be a unique presentation of a follicular adnexal neoplasm.

Two cases of systemic mantle cell lymphoma involving the skin.

Mantle cell lymphoma (MCL) is a form of non-Hodgkin lymphoma that rarely affects skin. Cutaneous involvement is non-specific but usually indicates widespread disease. Herein we present two cases of MCL with secondary skin involvement. One case presented as an acneiform eruption on the face and had aberrant expression of bcl-2 and bcl-6 with weak CD5 expression. The second presented with multiple tumors on the abdomen and thighs. In both cases expression of Cyclin-D1 by the tumor cells was seen. Both patients died shortly after the diagnosis was established.

Pseudoepitheliomatous Hyperplasia in a Red Pigment Tattoo: A Separate Entity or Hypertrophic Lichen Planus-like Reaction?

Red pigment tattoos are known to cause pseudoepitheliomatous hyperplasia in the skin, frequently simulating squamous cell carcinoma or keratoacanthoma. Herein, the authors present two additional cases of red pigment tattoo pseudoepitheliomatous hyperplasia in which they noted a lichenoid tissue reaction. They reviewed the previously published cases and observed a lichenoid reaction in the histopathological images similar to hypertrophic lichen planus. The authors suggest that these reactions might best be referred to as "lichenoid reaction with pseudoepitheliomatous hyperplasia" or "hypertrophic lichen planus-like reaction." Accordingly, recognition of an inflammatory component may allow additional treatment options.

Hyperkeratotic variant of porokeratosis in a patient with Hepatitis C virus infection and a concomitant immunosuppressed state.

Porokeratoses are acquired and hereditary disorders of keratinization that share a distinctive lesion characterized by raised keratotic borders corresponding histologically to an angled column of parakeratotic cells, called a cornoid lamella. Although a precise mechanistic explanation is lacking, ultraviolet radiation and immunosuppressed states are considered causally-associated with most cases of acquired porokeratosis. Hepatitis C virus (HCV) infection has been proposed as a link between the immunosuppressed states and development of acquired porokeratosis. Among the various recognized clinical entities that constitute this group, rare cases of hyperkeratotic variants have been described that may pose a diagnostic challenge. Herein we describe a remarkable case of the hyperkeratotic variant of porokeratosis that occurred in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state. We also provide a review of the relevant literature.

Histopathologic Distinguishing Features Between Lupus and Lichenoid Keratosis on the Face.

BACKGROUND: The occurrence of lichenoid keratosis (LK) on the face is not well characterized, and the histopathologic distinction between LK and lupus erythematosus (LE) occurring on the face is often indeterminate. The authors aimed to describe differences between LE and LK occurring on the face by hematoxylin and eosin alone. METHODS: Cases of LK and LE were obtained using computer-driven queries. Clinical correlation was obtained for each lupus case. Other diagnoses were excluded for the LK cases. Hematoxylin and eosin-stained sections were reviewed. RESULTS: Forty-five cases of LK and 30 cases of LE occurring on the face were identified. Shared features included follicular involvement, epidermal atrophy, pigment incontinence, paucity of eosinophils, and basket-weave orthokeratosis. Major differences between LK and LE, respectively, included perivascular inflammation (11%, 90%), high Civatte bodies (44%, 7%), solar elastosis (84%, 33%), a predominate pattern of cell-poor vacuolar interface dermatitis (7%, 73%), compact follicular plugging (11%, 50%), hemorrhage (22%, 70%), mucin (0%, 77%), hypergranulosis (44%, 17%), and edema (7%, 60%). A predominate pattern of band-like lichenoid interface was seen more commonly in LK as compared with LE (93% vs. 27%). CONCLUSIONS: The authors established the occurrence of LK on the face and identified features to help distinguish LK from LE. Follicular involvement, basket-weave orthokeratosis, pigment incontinence, paucity of eosinophils, and epidermal atrophy were not reliable distinguishing features. Perivascular inflammation, cell-poor vacuolar interface, compact follicular plugging, mucin, hemorrhage, and edema favored LE. High Civatte bodies, band-like lichenoid interface, and solar elastosis favored LK.