Exploring cutaneous lymphoproliferative disorders in the wake of COVID-19 vaccination.

Background: Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID-19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined. Objective: Determine if there are cases of cutaneous LPDs associated with certain COVID-19 vaccines and their outcomes. Methods: We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy-proven LPDs following COVID-19 vaccines. Results: Fifty cases of biopsy-proven LPDs arising after COVID-19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male-to-female ratio of 1.5:1). The Pfizer-BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near-complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision. Conclusion: LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Expanding the Differential Diagnosis of the Painful Nail: A Case of an Onychopapilloma with Neuroma.

Introduction: Onychopapilloma most commonly presents as longitudinal erythronychia, but diagnosis may be challenging in some cases due to varied clinical presentations. Most patients with onychopapillomas do not report associated pain but instead more commonly report functional interference. Case Report: We present a case of a 74-year-old female with a 5-year history of splitting and lifting of the right thumbnail, accompanied by nail sensitivity and intermittent painful throbbing. Clinical examination was significant for a less than 1 mm red line with distal onycholysis. Love's test and a cold test performed with ice pack were negative. X-ray of the right thumb was negative for erosion or exostosis. Nail biopsy was performed, and dermatopathology was consistent with onychopapilloma with a concomitant traumatic neuroma. Conclusion: We report a case of onychopapilloma with a concomitant traumatic neuroma. Subungual neuromas are extremely rare and have not previously been associated with onychopapilloma. Our case supports the expansion of the differential diagnosis for a painful nail and demonstrates the importance of diagnostic confirmation with biopsy and histopathology.

Subcutaneous panniculitic-like T-cell lymphoma localized to a site of peginterferon alfa-2a administration.

T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis.

Horrifying Basal Cell Carcinoma Presenting as Progressive Pyoderma Gangrenosum: Case Report.

Introduction: Skin ulcers can be challenging to diagnose and manage, particularly with comorbid autoimmune and gastrointestinal diseases. Occam's razor encourages the simplest explanation to guide care, but reconsideration must occur when intervention proves futile. Case Presentation: We report the case of a 70-year-old male, with a 17-year history of expanding pretibial skin ulcer, presumed by prior care providers to be pyoderma gangrenosum related to Crohn's disease. A surgical biopsy performed upon presentation to our institution revealed basal cell carcinoma of the skin, invasive to the proximal tibia with associated deep infection, prompting transfemoral amputation. Conclusion: This report is written as a reminder to reconsider a diagnosis and consider seeking additional expertise when a patient's condition progressively worsens despite intervention. Earlier diagnosis likely would have facilitated therapeutic limb salvage care.

Cutaneous lymphoproliferative disorders after COVID-19 vaccination: clinical presentation, histopathology, and outcomes.

Individual reports described lymphoproliferative disorders (LPDs) after COVID-19 vaccination; however, the relationship between cases is unexamined. We aim to determine if there are cases of cutaneous LPDs associated with COVID-19 vaccination and their outcomes. We present a review of world literature, vaccine registries, and two unreported cases of LPDs after COVID-19 vaccination. Review of the medical literature, VAERS, and our two cases reveal predominance of Pfizer-BioNTech vaccine, younger patients, and males. All cases resulted in favorable outcomes. Approximately 84% of cases demonstrated CD30+ positivity in their skin biopsies, suggesting that an antigenic trigger may lead to a type IV adaptive immune response, with clonal expansion of CD30+ T-cells and subsequent oncogenic mutational hits eventuating in transient LPDs. LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

TEMPI syndrome: A clinical, light-microscopic and phenotypic evaluation with review of the literature.

BACKGROUND AND OBJECTIVES: TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy. METHODS: We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53-year-oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis. RESULTS: A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment. CONCLUSIONS: TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.

Bullous Lichen Planus of the Nails: A Case Report and Review of the Literature.

Lichen planus is a chronic inflammatory disorder that may affect the skin, nails, and/or oral mucosa. Bullous lichen planus is a rare variant of lichen planus, which is even less common in the nails. We present a case of nail bullous lichen planus, in a 48-year-old male presenting with a 10-month history of onychodystrophy of all ten fingernails. A longitudinal excision of the left thumbnail was performed, with histopathology consistent with lichen planus with focal transition to bullous lichen planus. He was treated with intralesional triamcinolone injections to the fingernails monthly, with improvements noted after three treatments. Our patient's nail bullous lichen planus manifested with longitudinal ridging, white-yellow discoloration, onycholysis, subungual hyperkeratosis, and v-shaped nicking. Histopathological findings included classical lichen planus changes, as well as formation of subepidermal bullae, colloid bodies, and extensive inflammatory infiltrate. Increased awareness and high index of suspicion for this condition are necessary, given the often late diagnosis reported in previously published cases.

Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder: A clinical and histologic retrospective cohort study.

Clonally restricted, non-epidermotropic, low-grade, CD8-positive T-cell infiltrates of the skin was recognized as a unique form of indolent CD8-positive lymphoproliferative disease in 2007 when it was first called primary cutaneous indolent CD8-positive lymphoid proliferation. More recently, the designation of primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder has been used. It is unique as a cutaneous lymphoproliferative disorder because of relative uniformity in its clinical presentation and histomorphology. It has been recognized as having an interesting predilection for the ear and acral sites, characteristically presenting as a solitary lesion. The basic morphology is one characterized by a non-epidermotropic, tumefactive infiltrate of well-differentiated, noncerebriform, atypical, small- to intermediate-sized lymphocytes that exhibit a specific phenotype characterized by CD8 and TIA positivity in concert with a distinct perinuclear Golgi staining pattern for CD68. The typical presentation is in the context of a solitary lesion, which can be treated surgically or with local irradiation. We describe in detail two very unusual cases that expand the clinical spectrum of this condition given the non-acral localization, the multiplicity of lesions to involve the trunk and extremities, and, in one case, the stable but recalcitrant course over 30 years. In addition, the second patient developed paraneoplastic dermatomyositis. We also retrospectively review our database for other cases that represent the entity of primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder and review the literature focusing on non-acral cases. Nomenclature evolution from its first recognition in 2007 to the present is discussed.

Panniculitic primary cutaneous gamma delta T-cell lymphoma with concomitant features of autoimmune disease emphasizing a pathophysiologic continuum of lupus profundus with the panniculitic T cell lymphomas.

Certain T-cell lymphomas exhibit unique homing properties of the neoplastic lymphocytes for the subcutaneous fat. There are two primary forms of subcutaneous panniculitic lymphomas of T-cell origin. One falls under the designation of primary cutaneous gamma-delta T-cell lymphomas (PGD-TCL) whereby there is dominant involvement of the fat defininng a panniculitic form of PGD-TCL. The neoplastic cells are of the gamma-delta subset and are either double negative for CD4 and CD8 and/or can express CD8. They often have an aggressive clinical course. The other form of panniculitic T-cell lymphoma falls under the designation of subcutaneous panniculitis-like T-cell lymphoma (SPTCL). It represents a subcutaneous lymphoma derived from CD8+ T cells of the alpha-beta subset and typically has an indolent course. These two forms of panniculitic T-cell lymphoma exhibit overlapping histologic features with lupus profundus (LP), a putative form of panniculitic T-cell dyscrasia. We present three cases of PGD-TCL of the fat in the setting of lupus erythematosus (LE) (two cases) and dermatomyositis (DM) (one case), respectively. There were concurrent features of LE and DM in their lymphoma biopsies in two cases while a prior biopsy in one was interpreted as LP. In this latter case, the LP diagnosis presaged the diagnosis of panniculitic PGD-TCL by three years. One patient diagnosed with panniculitic PGD-TCL had hemophagocytic syndrome after developing a lupus-like complex including certain supportive serologies such as antibodies to double-stranded DNA following initiation of statin therapy. The second patient presented with PGD-TCL and concomitant features of anti-nuclear matrix 2 (NXP2) DM. The third patient presented in 2003 with LP and overlying skin features of acute LE, initially responding to Plaquenil, and then four years later was diagnosed with PGD-TCL heralded by Plaquenil treatment resistance. Two of the patients died of their lymphoma. All biopsies showed a characteristic histopathology of PGD-TCL. In two cases, the PGD-TCL was associated with overlying LE-cutaneous findings; another case had skin changes of lymphocyte-rich DM. In two cases, the MXA stain was strikingly positive, the surrogate type I interferon marker that is typically upregulated in biopsies of LE and DM. There are eight prior reported cases describing SPTCL with concomitant cutaneous changes of LE. In six cases there was an established history of LE, including LP responding initially to Plaquenil, similar to one of our cases. In the context of SPTCL or panniculitic PGD-TCL, panniculitic T-cell lymphomas can be associated with concomitant clinical and histologic features of LE or DM, including an upregulated type I interferon signature. Identifying histologic features associated with either of these prototypic autoimmune conditions should not be considered exclusionary to diagnosing any panniculitic T-cell lymphoma. A clinical, histomorphologic, and pathophysiologic continuum exists with LP, SPTCL and panniculitic PGD-TCL.

Nail Unit Arteriovenous Hemangioma Presenting as Longitudinal Erythronychia.

Introduction: Localized longitudinal erythronychia is defined as a single nail with a longitudinal red band extending the length of a nail plate. It has a broad differential of benign and malignant etiologies, and is rarely due to benign vascular proliferations. Case Presentation: We present a unique case of nail unit arteriovenous hemangioma presenting as longitudinal erythronychia of the left thumbnail in a 76-year-old male. The band was 6 mm and encompassed over 40% of the surface area of the nail plate. Dermoscopy showed red bands that were regular in terms of color, but not thickness or spacing. Due to concern for an amelanotic melanoma, a longitudinal excision was performed. Histopathology was consistent with a diagnosis of nail unit arteriovenous hemangioma. Conclusion: Arteriovenous hemangiomas were rarely present in the nail unit. They can be present as a blue or red nodule/macule, or as longitudinal erythronychia. Diagnosis often requires an excisional biopsy, with histopathology notable for a proliferation of multiple thick- and thin-walled vascular structures lined by a flattened endothelium. Our case emphasizes the need to consider vascular proliferations, such as arteriovenous hemangioma, in the differential diagnosis of longitudinal erythronychia.

Nail Unit Squamous Cell Carcinoma with Onycholemmal Features: Case Report and Review of the Literature.

Introduction: Onycholemmal carcinoma (OC) is a rare subtype of squamous cell carcinoma (SCC) that originates from the epithelium of the nail bed. It is characterized by distinct histopathologic features including small clusters of atypical squamous epithelium devoid of a granular layer, with abrupt onycholemmal keratinization. Case Presentation: We present a case of a 75-year-old male with right thumbnail onycholysis, yellow-green nail plate discoloration, as well as bleeding and purulence of the lateral nail fold. Histopathologic evaluation revealed high-grade squamous dysplasia, small clusters of severely atypical epithelial cells, and a pattern of abrupt keratinization consistent with the diagnosis of SCC carcinoma with onycholemmal features. GMS and PAS staining indicated concomitant onychomycosis. Pathologic analysis also disclosed residual SCC and concomitant amyloidosis, possibly light chain related and hence reflective of his underlying multi-organ lymphoplasmacytic lymphoma. The patient subsequently underwent Mohs micrographic surgery. Conclusion: Clinical presentation of nail unit SCC with onycholemmal features is highly variable, making differentiating between similarly presenting benign and malignant nail disorders particularly challenging. This case report demonstrates clinical and histopathological features of nail unit SCC with onycholemmal features to improve diagnosis and management.

Isolation of Terbinafine-Resistant Trichophyton rubrum from Onychomycosis Patients Who Failed Treatment at an Academic Center in New York, United States.

Onychomycosis is a common nail infection. Terbinafine-resistant dermatophyte infections pose an emerging global public health concern, but few cases have been described in the United States. We retrospectively reviewed and characterized clinical, histopathological, and mycological features of patients with mycologically confirmed onychomycosis who failed oral terbinafine treatment for onychomycosis at a U.S. academic nail referral center and ascertained for terbinafine-resistant isolates. During 1 June 2022-31 January 2023 at Weill Cornell Medicine in New York City, USA, 96 patients with mycologically confirmed onychomycosis were treated with oral terbinafine. Among 64 patients with adequate follow-up, 36 had clinical or complete cure. Of 28 patients who failed treatment, 17 underwent terbinafine resistance testing. Trichophyton rubrum with terbinafine resistance-conferring mutations was isolated from two patients. Overall, terbinafine failures for onychomycosis were relatively common, with some cases associated with terbinafine-resistant T. rubrum infections. These findings underscore the need for a clinical awareness of this emerging problem and public health efforts to monitor and prevent spread. We highlight the importance of diagnostic testing and species identification for onychomycosis patients and the increasingly important role of fungal identification and susceptibility testing to guide therapy.

Acral Fibrochondromyxoid Tumor Presenting as Enlarging Nodule Involving the Distal Fingertip and Hyponychium: A Case Report.

An acral fibrochondromyxoid tumor is a newly described type of benign soft tissue neoplasm that presents as a single nodular lesion on a finger or toe. There has only been one previous report on this tumor, a case series that described the initial pathologic and clinical findings; however, details on clinical history, physical examination, and outcome are unknown. In this report, we describe a case of a 39-year-old male who presented with a painful enlarging mass involving the distal right 3rd finger and hyponychium. Punch biopsy was performed and the lesion was identified as an acral fibrochondromyxoid tumor on microscopic examination. X-ray showed no bony involvement. The tumor was successfully excised with complete resolution of pain symptoms. We discuss the clinical features and immunohistochemistry findings of our case in the context of the current limited knowledge about this very rare tumor.

Primary cutaneous blastic marginal zone lymphoma: A comprehensive clinical, light microscopic, phenotypic and cytogenetic appraisal.

BACKGROUND: Primary cutaneous marginal zone lymphoma (PCMZL) is a form of indolent lymphoproliferative disease where the disease is largely a cutaneous confined process. It is typically a neoplasm composed of post germinal small B-cells and light chain restricted plasma cells in a background of reactive T-cell hyperplasia and benign germinal centers. Rarely a significant degree of large cell infiltration occurs warranting the categorization as blastic marginal zone lymphoma. MATERIALS AND METHODS: We reviewed our data base over a time period of 2016 to 2022 for cases diagnosed as blastic MZL. Twelve cases were identified. The clinical records and pathological data were reviewed. RESULTS: Nine of the cases represented de novo forms of blastic MZL while in three cases there was a prior history of MZL. Multifocal cutaneous disease was not uncommon and one quarter of the cases had evidence of extracutaneous dissemination. All patients except three achieved remission with varied therapeutic interventions depending on the extent of the disease ranging from conservative re-excision to chemotherapy. No patient died from lymphoma. Light microscopically, there was evidence of a background of conventional MZL in the majority of cases. The large cell component was typically characterized by multiple micronodular aggregates throughout the dermis although in three cases there was a striking diffuse large cell component as the dominant infiltrate. Phenotypically, a third of the cases showed either CD5 or CD23 positivity amidst neoplastic B cells. Significant staining for BCL-2 was noted in the majority of cases tested while extensive MUM-1 positivity was observed in half of the cases tested. Kappa or lambda light chain restriction was seen in most. The Ki67 proliferation index exceeded 30 % in all cases. There was C-MYC positivity in two cases. While most cases did not detect cytogenetic abnormalities, one case had multiple cytogenetic hits that are associated with diffuse large B cell lymphoma. Next generation sequencing showed a Ten-eleven translocation 2 mutation in the earlier biopsy prior to transformation and in the later biopsy after transformation along with an additional B2M mutation in the transformed biopsy. Both types of mutations are very uncommon but held to contribute to tumor progression in the setting of diffuse large B cell lymphoma. CONCLUSION: Blastic MZL is associated with a more aggressive clinical course. Even when there is disseminated disease patients while not always cured did not have a fatal course in this series. The light microscopic findings are reproducible. The background of MZL, identification of larger cells in significant numbers without a follicle center phenotype, at times expressing CD5 or CD23 with variable positivity for MUM1, BCL-2 and C-MYC and a high proliferation index define the pathology in most. Certain cytogenetic abnormalities and genetic mutations implicated in large cell transformation into a diffuse large B cell lymphoma are seen in blastic MZL with earlier biopsies prior to transformation potentially harboring at risk genetic mutations.