Two Squamomelanocytic Tumors With Dendritic Melanocytes: Thoughts About Origin.

ABSTRACT: Cutaneous malignant squamomelanocytic tumor (SMT) is a rare neoplasm comprising 2 distinct cell populations of squamous cell carcinoma and a second component of either benign or malignant melanocytes. SMT most often presents as a keratotic papule in areas of chronic sun exposure, typically on the head or neck of middle-aged and elderly-aged, White male patient populations. In recent years, there has been an increase in case reports, including a review article published in 2023, identifying a total of 37 cases published in the literature. There are only 3 reported cases in the literature with spindled or dendritic cells in the melanocytic component, as most have been of the epithelioid subtype. Despite the increasing prevalence, the origin and pathophysiology is poorly understood. We report 2 cases of SMT with dendritic melanocytes that are centered around a hair follicle, proposing the theory that these 2 distinct cell types may arise from the hair follicles.

An Unexpected Post-Egg-Free Influenza Vaccine Granulomatous Reaction.

ABSTRACT: A 53-year-old woman presented with a pruritic plaque on the left upper arm that appeared following an egg-free flu vaccine due to a history of reaction to the standard vaccine. The affected area enlarged over a several month period immediately following vaccine administration. Physical examination revealed an 8 × 4 cm coalescent pink plaque on the left upper arm. A shave biopsy of the lesion showed dermal "naked" granulomas, or granulomas with sparse lymphocytic infiltrate at the margins, as typically seen in sarcoidosis. No foreign material was seen in the granulomatous reaction, including with polarization. Special stains, including acid fast bacilli, Grocott methenamine silver, periodic acid-Schiff, and Gram, were negative for organisms. The diagnosis of granulomatous dermatitis was made. Subsequent imaging demonstrated no findings suggestive of sarcoidosis. While vaccine-associated hypersensitivity reactions occur frequently, these reactions are typically due to individual vaccine components, such as egg protein, and do not normally result in the formulation of granulomas. Vaccination-induced granulomas are more often associated with the use of aluminum as an adjuvant; however, this is not present in the egg-free influenza vaccine. Thus, a granulomatous reaction to the egg-free influenza vaccine is very unusual and, to our knowledge, not previously reported.

Non-psoriatic uses of calcipotriol: a concise updated review.

Calcipotriol (calcipotriene) is a synthetic vitamin D3 derivative that is a standard treatment option for psoriasis. It is generally well tolerated with minimal side effects. Due to its ability to reduce keratinocyte proliferation and induce keratinocyte differentiation as well as its immunomodulatory effects, calcipotriol has been used to treat a variety of skin disorders such as atopic dermatitis, actinic keratoses, lichen planus, seborrheic keratoses, and vitiligo [1]. We surveyed the literature examining the use of calcipotriol for non-psoriatic dermatologic disease.

An Extraordinary Cause of Colonic Obstruction: Merkel Cell Carcinoma of Unknown Primary.

Merkel cell carcinoma is an aggressive and rare neuroendocrine skin cancer with documented metastases to the liver, lungs, and, seldom, the gastrointestinal tract. Metastases to the colon are rare but are seen with primary skin lesions or recurrent disease. Presented is a patient with large bowel obstruction secondary to a large hepatic flexure mass. Pathologic workup revealed Merkel cell carcinoma, and a dermatologic evaluation did not identify a primary cutaneous lesion. This is the first reported case of Merkel cell carcinoma of unknown primary presenting as large bowel obstruction.

Papuloerythroderma of Ofuji in a Young Man.

Papuloerythroderma of Ofuji (PEO) is a rare skin disorder characterized by a distinctive pattern of pruritic, flat-topped, erythematous papules which coalesce into an erythroderma-like eruption with classic sparing of the skin folds. Although the pathogenesis of this condition is incompletely understood, previous reports have suggested a notable link between PEO and various forms of malignancy and immunocompromised states. Here, we report a case of a healthy young male with no comorbidities who presented with the classical features of PEO that responded well to combination therapy comprised of topical corticosteroids and phototherapy.

Myxoid perineurioma: an entity with many mimics.

We present a case of a female patient who presented with a 0.6cm flesh-colored "rubbery" papule on the left thigh. Biopsy revealed a dermal myxoid tumor containing spindled cells, tapered nuclei, indistinct cell borders, and a large number of mast cells. The spindle cells stained negative for S100 protein and Sox10 on immunohistochemistry, excluding myxoid neurofibroma, but positive for epithelial membrane antigen (EMA), and CD34, supporting a diagnosis of myxoid perineurioma. Interestingly, the mast cells showed cytoplasmic and nuclear positivity for microphthalmia transcription factor (MiTF). The lesion was fully excised one year later with identical histopathology and ancillary immunohistochemical profile.

Pseudolymphoma to Lymphoma: A Case of Chronic Reactive Lymphoid Hyperplasia Transforming to Primary Cutaneous Marginal Zone Lymphoma.

ABSTRACT: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that originates from the skin. It often presents as erythematous solitary or multiple papules, nodules, and/or plaques. It is one of the 3 main subtypes of primary cutaneous B-cell lymphomas. PCMZLs are believed to develop from chronic antigenic stimulation such as from tick-borne bacteria, vaccines, tattoo pigment, or other foreign body. In addition, cutaneous lymphoid hyperplasia, a documented precursor to malignant PCMZL, often presents in response to areas of chronic inflammation. Cutaneous lymphoid hyperplasia and PCMZL share several clinical and histological similarities that require clinicopathologic suspicion, immunohistochemical ancillary studies, and histopathologic analysis to accurately differentiate the 2 entities. Although gene rearrangement studies have historically been of limited value in the diagnosis of PCMZL, recent studies investigating molecular markers have identified the presence of multiple genetic abnormalities that have helped to better characterize the disease and aid in diagnosis. In addition, newer studies have found associations between PCMZL and gastrointestinal disorders, including Helicobacter pylori and inflammatory bowel disorders. In this article, we describe a case of a 56-year-old patient with a history of ulcerative colitis presenting with chronic reactive lymphoid hyperplasia that transformed to primary cutaneous marginal zone lymphoma.

Interstitial Mycosis Fungoides: An Unusual Mimic of Interstitial Granuloma Annulare Not to Miss.

Interstitial mycosis fungoides is a rare histopathologic variant of mycosis fungoides that may resemble interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Reported is a case of a 62-year-old African American female who presented with an asymptomatic, progressive rash of the left underarm and abdomen with histologic features suggestive of granuloma annulare. Biopsies revealed an interstitial pattern of cells in the dermis with prominent small aggregates of atypical lymphocytes, a few atypical lymphocytes in the lower epidermis, and a mild increase in dermal mucin. Immunohistochemistry staining revealed the atypical lymphocytes to be positive for CD3 and CD8 and negative for CD4 and CD7, an aberrant immunoprofile. Mixed in the dermis with the atypical lymphoid cells were a few CD68 positive histiocytes and S100 protein positive dermal dendritic cells. T-cell receptor beta gene rearrangement studies showed nearly the same clonal peaks for TCRB rearrangement in two biopsy specimens from separate sites, all supporting a diagnosis of interstitial mycosis fungoides. The patient is undergoing treatment with full body narrowband UVB (nbUVB) phototherapy with notable improvement in skin discoloration and resolution of several abdominal lesions. A diagnosis of interstitial mycosis fungoides is challenging to make based on clinical features alone and is often clinically misdiagnosed. Awareness of histopathologic features is critical to make an accurate diagnosis and thus patient management.

Treating linear porokeratosis with topical lovastatin/cholesterol cream.

Linear porokeratosis is a rare variant of porokeratosis that is characterized by unilateral lesions along the lines of Blaschko. Like all variants of porokeratosis, linear porokeratosis is characterized by the histopathologic finding of cornoid lamellae bracketing the lesion. The underlying pathophysiology involves a two-hit post-zygotic knockdown of genes involved in mevalonate biosynthesis in embryonic keratinocytes. Although there is currently no standard or effective treatment, therapies targeted to rescue this pathway and restore keratinocyte cholesterol availability are promising. Presented here is a patient with a rare, extensive case of linear porokeratosis treated with compounded 2% lovastatin/2% cholesterol cream leading to partial resolution of the plaques.

Estrogen Receptor ß Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors. The ER is an organelle that serves essential roles in protein modification, folding, and maturation of proteins; however, the specific role of ER stress in altered social behavior is unknown. In this study, treatment with tunicamycin, an ER stress inducer, enhanced the phosphorylation level of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1) and increased X-box-binding protein 1 (XBP1) mRNA splicing activity in the mouse PFC, whereas inhibition of IRE1/XBP1 pathway in PFC by a viral particle approach attenuated social behavioral deficits caused by tunicamycin treatment. Reduced estrogen receptor beta (ERß) protein levels were found in the PFC of male mice following tunicamycin treatment. Pretreatment with an ERß specific agonist, ERB-041 significantly attenuated tunicamycin-induced deficits in social behavior, and activation of IRE1/XBP1 pathway in mouse PFC. Moreover, ERB-041 inhibited tunicamycin-induced increases in functional connectivity between PFC and hippocampus in male mice. Together, these results show that ERß agonist attenuates ER stress-induced deficits in social behavior through the IRE-1/XBP1 pathway.

Complement C3 Expression Is Decreased in Autism Spectrum Disorder Subjects and Contributes to Behavioral Deficits in Rodents.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels in the middle frontal gyrus of ASD subjects compared to controls. Significant decreases in the mRNA levels of 2 key proinflammatory cytokines, IL-17 and IL-23 were observed in ASD subjects. Our study further demonstrated a strong association of complement genes with IL-17 and IL-23, suggesting a possible role of the complement system in immune dysregulation in ASD. We observed significant associations between complement components and abnormality of development scores in subjects with ASD. In rodents, C3 knockdown in the prefrontal cortex induced social interaction deficits and repetitive behavior in mice. Together, these studies suggest a potential role of C3 in the pathophysiology of ASD.