Cytophagic histiocytic panniculitis leading to a diagnosis of acute myeloid leukemia with monocytic differentiation: A case report and literature review.

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

Calciphylaxis and Kidney Disease: A Review.

Calciphylaxis is a life-threatening complication most often associated with chronic kidney disease that occurs as a result of the deposition of calcium in dermal and adipose microvasculature. However, this condition may also be seen in patients with acute kidney injury. The high morbidity and mortality rates associated with calciphylaxis highlight the importance to correctly diagnose and treat this condition. However, calciphylaxis remains a diagnosis that may be clinically challenging to make. Here, we review the literature on uremic calciphylaxis with a focus on its pathophysiology, clinical presentation, advances in diagnostic tools, and treatment strategies. We also discuss the unique histopathological features of calciphylaxis and contrast it with those of other forms of general vessel calcification. This review emphasizes the need for multidisciplinary collaboration including nephrology, dermatology, and palliative care to ultimately provide the best possible care to patients with calciphylaxis.

Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island.

INTRODUCTION: Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. METHODS: We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80 years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. LIMITATIONS: Study patients were predominantly White and from a single institution, limiting the generalizability of results. CONCLUSIONS: Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up.

Understanding melanoma in situ: Lentigo maligna surgical treatment terminology and guideline adherence, a targeted review.

BACKGROUND: Malignant melanoma in-situ, lentigo maligna (MMIS-LM) can be successfully treated with several different surgical techniques; however, the literature is inconsistent in defining them. OBJECTIVE: To comprehensively define and describe the national guideline recommended surgical techniques used to treat MMIS-LM to help clarify and standardize this terminology to ensure compliance with the guidelines. METHODS: A targeted literature review was performed from 1990 to 2022 focusing on articles that discussed the national guideline recommended surgical techniques of wide local excision, Mohs micrographic surgery (MMS), modified Mohs surgery, and staged excision/Slow-Mohs for MMIS-LM, as well as the related methods of tissue processing. National Comprehensive Cancer Network and American Academy of Dermatology guidelines were reviewed to identify how the techniques need to be employed to be compliant with guideline recommendations. RESULTS: We describe the various surgical and tissue processing techniques and discuss advantages and disadvantages of each. LIMITATIONS: This paper was styled as a narrative review defining and clarifying terminology and technique and does not investigate these topics more broadly. CONCLUSION: Understanding the methodology and terminology for these surgical procedures and tissue processing methods is critical so that both general dermatologists and surgeons can employ these techniques effectively for optimal patient care.

Cutaneous Sporothrix globosa infection mimicking cryptococcosis in a patient with history of kidney transplant.

Sporotrichosis is a subacute-to-chronic infection caused by Sporothrix species, a dimorphic fungus. Virulence varies by Sporothrix species and presentation can be region dependent. The patient had a history of immunosuppression as a result of a kidney transplant, and presented with a high disease burden on histopathological examination, but responded well to itraconazole. The case suggests considering Sporothrix speciation in immunocompromised patients to best determine treatment modality and duration.

Segmental basaloid follicular hamartomas derive from a post-zygotic SMO p.L412F pathogenic variant and express hair follicle development-related proteins in a pattern that distinguish them from basal cell carcinomas.

Basaloid follicular hamartomas (BFH) are benign small basaloid skin tumors that can present as solitary or multiple lesions. Congenital BFH lesions arranged in a segmental distribution have been described, suggesting they derive from a somatic post-zygotic mutational event. Previously, BFH were described in Happle-Tinschert syndrome, which results from a post-zygotic SMO variant and is characterized by segmental BFH with variable involvement of the teeth, skeleton, and central nervous system. Here, we describe two patients with isolated segmental BFH and no systemic involvement. Paired whole exome sequencing of BFH and normal tissue revealed a pathogenic SMO c.1234 C>T, p.L412F variant restricted to BFH tissue. We characterized the proliferation index and expression of Hedgehog and Wnt/beta-catenin pathway related proteins in segmental BFH compared to sporadic basal cell carcinomas (BCCs) and found that segmental BFH had a lower proliferation index. Although segmental BFH expressed a similar level of Gli-1 compared to BCCs, levels of LEF-1 and SOX-9 expression in BFH were weaker for both and patchier for LEF-1. Our results show that a somatic SMO activating variant causes segmental BFH. Since these patients are prone to developing BCCs, differences in SOX9, LEF1, and Ki-67 expression can help distinguish between these two basaloid lesions.

Concominant bullous pemphigoid and cutaneous Crohn disease.

We report a case of new-onset bullous pemphigoid manifesting concurrently with cutaneous Crohn disease in a 58-year-old woman. Cutaneous Crohn disease is an extraintestinal manifestation of Crohn disease characterized by non-specific plaques or nodules. Bullous pemphigoid, a sub-epidermal autoimmune blistering disorder, has been observed in the setting of inflammatory bowel disease. The patient presented with recurrent bullae on the abdomen, thighs, and buttocks of 1 year's duration. She was not on any immunosuppressive therapies and had been treated with infliximab and azathioprine for her Crohn disease, which were discontinued 8 years before the blistering commenced. Punch biopsy of lesional skin showed a sub-epidermal blister with eosinophils. Sarcoidal and tuberculoid granulomas were present in the dermis. Direct immunofluorescence revealed linear 2+ IgG and 3+ C3 along the basement membrane. Indirect immunofluorescence was positive for BP180 and BP230 antibodies. These findings support the diagnosis of bullous pemphigoid with concomitant cutaneous Crohn disease. Both bullous pemphigoid and Crohn disease have been associated with an altered T-cell response. The similarities in the pathogenesis of the underlying inflammatory milieu suggest a possible etiopathogenic connection. This is believed to be the first report of cutaneous Crohn disease presenting simultaneously with bullous pemphigoid on histopathological examination.

"Kissing" basaloid follicular hamartomas of the eyelid.

Basaloid follicular hamartomas (BFHs) are rare, benign, cutaneous adnexal tumors characterized by branching cords and anastomosing strands of basaloid cells in a loose, fibrous stroma. BFHs exhibit variable clinical presentations although they are commonly observed as skin-colored papules and are diagnosed based on histopathological features. Common systemic diseases associated with BFH include alopecia, myasthenia gravis, and palmoplantar pitting. BFH of the eyelid is extremely rare with only five cases reported in the literature to date. Congenital "kissing" lesions have only previously been reported with nevi. Here, we present a novel case of congenital "kissing" BFH of the right upper and right lower eyelid, and histopathological examination revealed intradermal nodules of basaloid cells forming reticulated strands, pseudohorn cysts, mucinous stroma, and palisading with CD34 and Bcl-2 expression in the stromal fibroblasts and periphery, respectively.

Paracicatricial melanocytes as a sign of melanoma.

Intradermal melanocytes in the setting of melanoma represent a diagnostic challenge to dermatopathologists as their presence may represent superficially invasive melanoma vs benign nevus cells or reactive dermal melanocytes. Previous dermatologic literature suggests that the absence of cytologic atypia in intradermal melanocytes and their presence in nonmelanocytic neoplasms lends to their characterization as reactive, benign, melanocytic proliferation. A 67-year-old female presented for evaluation of a 10-mm irregularly pigmented dark brown macule on the left cheek. Initial shave biopsy showed transected malignant melanoma measuring at least 0.6 mm in thickness. Multiple reexcision specimens demonstrated residual melanoma with banal appearing intradermal epithelioid melanocytes within and surrounding the scar. The melanocytes tracked into the skin graft, which had previously been free from involvement. Positron emission tomography-computed tomography (PET CT) and lymph node biopsies did not show evidence of metastatic melanoma. Ten months after her diagnosis and following five surgical excisions, the patient was diagnosed with metastatic melanoma to the brain and succumbed to intracranial hemorrhage. We present a case in which paracicatricial melanoma may simulate benign paracicatricial melanocytic hyperplasia. These findings have significant therapeutic and prognostic implications for the practicing dermatologist and dermatopathologist.

Localized Medium-Vessel Vasculitis From a Tick Bite.

ABSTRACT: Tick bites are known to induce a variety of inflammatory reaction patterns. Here, we present a novel case of medium-vessel vasculitis as a localized response to a known tick bite. It is important to recognize the histology associated with a tick bite response to prevent misdiagnosis and potential overtreatment of a vasculitic condition.

Secondary Syphilis With Elastophagocytosis: An Unusual Histologic Finding.

ABSTRACT: Elastophagocytosis is a characteristic finding of granulomatous and elastolytic disorders. It is defined by phagocytosed elastic fibers within histiocytes, multinucleated giant cells, or both. This finding has also been associated with certain medications, malignancies, inflammatory conditions, and infectious disorders. Although Drs Ragaz and Ackerman reported elastophagocytosis in a secondary syphilis lesion in a review of actinic granuloma in 1979, more recent publications have not recognized this finding. We present a case of elastophagocytosis within a lesion of secondary syphilis in a 65-year-old man. Biopsy from his left forearm demonstrated features of secondary syphilis including subtle vacuolar alteration with mild superficial and mid perivascular lymphoplasmacytic inflammation. There were interstitial giant cells with phagocytosed elastic fibers within the superficial dermis. Spirochete immunostain was positive with confirmatory Treponema pallidum IgG antibody and RPR titer. In this report, we present a unique case of secondary syphilis.

Aggressive CD4/CD8 Double-Negative Primary Cutaneous T-Cell Lymphoma With Dural Invasion: A Rare Presentation of Mycosis Fungoides?

ABSTRACT: Mycosis fungoides (MF) is primarily characterized by epidermotropic CD3+/CD4+/CD45RO+ memory T cells. CD4/CD8 double-negative MF is an uncommon variant with no presumed prognostic significance. Despite the variability in the clinical course and presentation of MF, most cases behave indolently. About 5% of patients, however, advance to stage IV with visceral organ involvement. Central nervous system metastasis in MF is rare with no known cases of direct central nervous system invasion by MF to date. We report an exceedingly rare locally aggressive case of CD4/CD8 double-negative MF with direct dural invasion and underline pertinent diagnostic challenges encountered in our case.

Two cases of congenital dermatomyofibroma.

We present two infants with histologically confirmed congenital dermatomyofibromas. Congenital cases are rare with only one prior case reporting presence since birth. Given the benign nature of the lesions and propensity of dermatomyofibromas to resolve without intervention in young male patients, no additional treatments were pursued.

A Rare Perineurioma/Granular Cell Tumor Hybrid Peripheral Nerve Sheath Tumor.

Hybrid peripheral nerve sheath tumors (PNSTs) are rare benign composite neoplasms demonstrating features of multiple endogenous nerve sheath cell types. Hybrid PNSTs with granular cell components are exceedingly rare. Only a handful number of hybrid PNSTs composed of granular cell tumor and perineurioma have been described to date. We present a rare hybrid of perineurioma and granular cell tumor and review the literature.

Signet-ring squamous cell carcinoma: a report of a rare variant and review of the literature.

Signet-ring squamous cell carcinoma is a rare histological subtype of squamous cell carcinoma. The distinct morphologic appearance of this variant can mimic metastatic adenocarcinoma and impose a diagnostic challenge. Unlike its glandular counterpart, signet-ring cell variant of squamous cell carcinoma has a poorly characterized histopathogenesis with no known prognostic implication. We describe an additional case and review the literature.

GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation.

Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention.

Four Diseases, Two Associations, One Patient: A Case of Frontal Fibrosing Alopecia, Lichen Planus Pigmentosus, Acne Rosacea, and Morbihan Disease.

A 77-year-old woman born in the Dominican Republic presented with fullness of the glabella and medial eyebrows for 1 year followed by alopecia of the lateral eyebrows and frontal hairline. She stated that although she had a high hairline at baseline, it had receded in the past year. She had also noted central scalp hair thinning that started 6 years earlier. She denied all styling practices that used traction or chemical processes, although she admitted to hair dye and blow dryer use. She reported "acne" in the central face for decades and darkening of the skin on the lateral face for several years. Her medical history included hypertension, hyperlipidemia, hypothyroidism, benign paroxysmal positional vertigo, and treated breast ductal hyperplasia. Her medications were metoprolol, amlodipine, aspirin, levothyroxine, omeprazole, pravastatin, and meclizine; she denied starting any new medications within the past 2 years. Her family history was notable for androgenic pattern alopecia in a brother and a high hairline in her father. Review of systems was negative except for knee arthralgias and seasonal allergic rhinitis.