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.
Bilateral tennis toe Falotico, Julianne M; Magro, Cynthia M; Lipner, Shari R
Indian journal of dermatology, venereology, and leprology,
11/2023, Letnik:
89, Številka:
6
Journal Article
The 2005 classification of lymphoma proposed the designation of subcutaneous panniculitis-like T-cell lymphoma exclusively for those tumors composed of α/β neoplastic cells. Subcutaneous lymphomas ...that comprised γ/δ T cells are termed primary cutaneous γ/δ T-cell lymphoma. The different clinical outcomes justified this separation; a more indolent course was characteristic of the α/β variants vs the poor 5-year survival of the γ/δ forms. We describe 5 patients with γ/δ T-cell lymphoma localized to the subcutis with a less aggressive clinical course. Two patients were alive 5 years after presentation, and in the remaining 3, the disease is in complete remission after simple intervention. Three patients had a waxing and waning phase, likely representing a prelymphomatous phase, which then progressed to an overt malignant tumor. Therefore, it is important to recognize that not all patients with γ/δ T-cell lymphomas have a poor prognosis.
Background
Checkpoint inhibitor therapy is widely known to cause a number of immune‐related adverse events. One rare adverse effect that is emerging is eosinophilic fasciitis, a fibrosing disorder ...causing inflammatory infiltration of subcutaneous fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. The condition is rare, yet at our institutions we have seen four cases in the past 3 years. We describe our 4 cases and review 11 other cases reported in the literature.
Case Presentation
We present four cases of eosinophilic fasciitis following treatment with programmed cell death protein 1 or programmed cell death‐ligand 1 blockade. All patients had extremity involvement with characteristic skin changes ranging from peripheral edema to induration, tightening, and joint limitation. The patients had varying degrees of peripheral eosinophilia. In two of our patients, the diagnosis was made by full‐thickness skin biopsy showing lymphocytic infiltration of the subcutaneous fascia, with CD4+ T cells predominating in one case and CD8+ T cells in the other. In the other two cases, the diagnosis was made on the basis of characteristic imaging findings in the context of clinical features consistent with the diagnosis. All four patients were treated with glucocorticoids with varying degrees of success; immunotherapy had to be discontinued in all four. Patients with advanced melanoma who experienced this adverse effect had either a partial response or a complete response to therapy.
Conclusion
Eosinophilic fasciitis can occur as a result of checkpoint inhibitor therapy. Although a tissue diagnosis is the gold standard, imaging studies may facilitate the diagnosis in the presence of consistent clinical features, but a degree of suspicion is key to recognizing the condition early. Therapy requires a collaborative approach by oncology, rheumatology, and dermatology; physical therapy is an important adjunct in treatment. For advanced melanoma, it may be a good prognostic indicator.
Implications for Practice
It is important for clinicians to recognize that eosinophilic fasciitis is a potential immune‐related adverse event (irAE) as a consequence of immune checkpoint inhibitor therapy. The presentation is quite stereotypical; the diagnosis can be made by imaging in the absence of a full‐thickness skin biopsy. Early intervention is important to limit morbidity. This irAE may be a good prognostic sign among patients with melanoma.
Eosinophilic fasciitis is an adverse effect of checkpoint inhibitor therapy. This article describes four cases of this rare adverse event and reviews the eleven cases reported in the literature to date.
Primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSTCL) has recently emerged as a distinct clinicopathological entity. Because of a considerable degree of overlap with ...pseudolymphoma, the diagnosis is often challenging. Preliminary studies suggest that nuclear upregulation of calcineurin/nuclear factor of activated T cells (NFAT) may play a role in lymphomagenesis.
137 cases (70 males and 67 female, mean age = 55) of various forms of cutaneous T-cell and B-cell infiltration were evaluated for NFATc1 expression. The study comprised 18 cases of PCSTCL, 45 cases of mycosis fungoides (MF), 5 cases of lymphomatoid papulosis (LyP), 5 cases of anaplastic large-cell lymphoma (ALCL), 8 cases of other forms of peripheral T-cell lymphoma, not otherwise specified, 12 precursor lesions of MF (ie, cutaneous T-cell dyscrasias), 35 cases of pseudolymphomas, 8 primary cutaneous B-cell lymphoma, and 1 chronic lymphocytic leukemia. The number of cells exhibiting a nuclear stain was counted per 10 high-power field and 2-tailed statistical analysis was used for comparison of nuclear NFATc1 expression between primary PCSTCL and all other groups. A P-value <0.05 was considered to indicate statistical significance.
All cases of PCSTCL showed nuclear staining for NFATc1 (mean = 296 ± 236) with no cases in which an exclusive cytoplasmic stain was observed. The cells exhibiting this staining pattern were oftentimes larger manifesting other features of a follicular helper T-cell phenotype, such as variable positivity for PD1, ICOS, CXCL13, and BCL6. In comparison, an exclusively cytoplasmic stain was observed in 29 cases of MF; in few cases, rare nuclear staining cells were observed averaging less than 10 per high-power field (P = 0.0001). These positive staining cases were not only limited to tumor-stage MF but also encompassed patch- and plaque-stage lesions and follicular variants of MF. The same pattern was observed in cases of T-cell dyscrasia (mean = 3 ± 3, P = 0.0001) and pseudolymphoma (mean = 2 ± 3, P = 0.0001), both revealing a dominant cytoplasmic staining pattern. In pseudolymphomatous folliculitis, a greater extent of nuclear staining for NFATc1 was observed compared with other forms of pseudolymphoma. No significant difference was seen between MF and T-cell dyscrasia or pesudolymphomas excluding pseudolymphotous folliculitis. Anaplastic large-cell lymphoma cases showed an almost exclusive cytoplasmic staining pattern with rare nuclear staining (mean = 55 ± 102, P = 0.0001); similar results were observed in LyP (mean = 17 ± 15, P = 0.004). Cutaneous B-cell lymphomas showed a similar extent of staining as that noted for PCSTCL. The greatest extent of staining was observed in chronic lymphocytic leukemia. A significant difference was noted between the extent of nuclear staining in PCSTCL and other forms of primary cutaneous T-cell lymphoma, type unspecified (mean = 22 ± 43, P = 0.0002), although not between PCSTCL and B-cell lymphoma.
NFAT signaling plays a critical role in peripheral T-cell activation after T cell receptor engagement. When assessing T-cell-rich infiltrates where the differential diagnosis is largely between a PCSTCL and pseudolymphoma, a significant degree of nuclear staining of lymphocytes would be more in keeping with a diagnosis of PCSTCL. Upregulation of the NFAT pathway is not a feature of tumor progression in the setting of MF.
Lichen sclerosus (LS) is a cutaneous disease of unknown etiology that often involves the vulva or foreskin but also can affect extragenital sites. Regardless of the anatomic site, the histomorphology ...and presumably pathogenesis are similar. Perhaps a clue to the pathophysiology of LS lies in its frequent association with morphea, specifically, when occurring in an extragenital context. In our experience a striking feature evident in established lichen sclerosis (LS) is one of superficial vascular drop out whereby residual vessels exhibited endothelial cell necrosis and microvascular basement membrane zone thickening, the latter reflective of antecedent episodes of microvascular injury. We sought to understand the pathophysiology that underlies the distinct vascular changes and in doing so, shed light on the pathogenesis of LS. We examined 44 cases of LS over a period of 2019 to 2021. We were able to obtain past medical histories in 34 of the 44 cases. Regarding pathological assessment, the predominant focus was on microvascular changes. We assessed the role of C5b-9 mediated vascular injury in the pathogenesis of the vasculopathy and enhanced type I interferon signaling in vessels given the morphologic semblance to the select interferonopathy syndromes, namely fibrosing dermatomyositis and Kohlmeier Degos disease. We examined the expression of CMV DNA and protein based on prior observations in an earlier study that isolated early protein expression in the microvasculature in the setting of LS and scleroderma. From a clinical perspective, the most striking association was an older age at the time of diagnosis (mean age of 62 years and median age of 61.5 years) and the presence of vascular comorbidities of diabetes, hypertension, and hyperlipidemia in almost 80% of cases. All cases showed significant microvascular changes in the superficial corium with the most frequent findings being those of significant basement membrane zone reduplication and vascular drop out. A number of cases showed prominent microvascular deposits of C5b-9 in the zone of hyalinizing fibrosis or subjacent to the discernible table of fibroplasia in the absence of enhanced type I interferon signaling. In no case were there viral cytopathic changes associated with CMV affecting the endothelium. The studies that encode CMV DNA or protein did not show a significant role for CMV reactivation in endothelium in the majority of the studied cases. It is concluded that the pathophysiology of LS includes a microvascular injury syndrome within the papillary dermis. The mechanism of endothelial cell injury is complement mediated at least in part and could reflect an adaptive immune response targeting endothelium indicative of classic complement pathway activation when coexisting with morphea or occurring in younger individuals. A non-immune based endothelial dysfunction and complement mediated injury unrelated to antibody driven classic complement pathway activation are more likely pathogenetically in the setting of certain diseases like diabetes mellitus and hypertension. Vascular drop out can be explained by the diminished endothelial progenitor pool needed to repopulate the damaged microvessels in certain settings like hypertension and diabetes.
•Lichen Sclerosus•Microvascular Injury•C5b-9•Complement•Diabetes
Abstract Background Lymphocytic thrombophilic arteritis is a recently recognized subcuticular larger vessel vasculitis characterized by striking vascular luminal thrombosis. Methods The clinical ...features, histopathology and phenotypic profile of ten patients with lymphocytic thrombophilic arteritis were explored in an attempt to better define the entity from a clinical and pathophysiologic perspective. Results The patients were all female (mean age of 43) presenting with generally asymptomatic lower and upper extremity hyperpigmented macules. A consistent picture diagnostic of a connective tissue disease syndrome was not seen. The disease was not progressive although it was typically persistent. The morphology was characterized by a temporally heterogeneous subcutaneous arteritis targeting the endothelium and intima with changes ranging from incipient intimal expansion by hyaluronic acid to concentric intimal fibrin deposition to one of an end stage acellular intraluminal obliterative fibrous arteriopathy. The infiltrate was predominated by lymphocytes and histiocytes. The intimal elastic lamina was intact in most cases. All tested cases showed intimal and endothelial C5b-9 deposition, an upregulated type I interferon microenvironment and marked upregulation of the inducible interferon gamma 16 protein. Conclusions Lymphocytic thrombophilic arteritis is a unique form of C5b-9 mediated arteritic endotheliopathy where the brunt of the changes involves the endothelium and intima and that is morphologically distinct from the transmural arteritis of benign cutaneous polyarteritis nodosa.
There is a growing recognition that some primary cutaneous T cell lymphomas of the skin exhibit a follicular helper T cell phenotype best exemplified by primary cutaneous CD4+ small/medium sized ...pleomorphic T cell lymphoma. The follicular helper T cells is an evolutionary function in a common TH1 cell under the influence of other cell types most notably monocyte derived dendritic cells but also plasma cells. In addition, the skin defines a characteristic organ site of involvement for angioimmunoblastic T-cell lymphoma (AITL); the first recognized form of follicular helper T cell lymphoma.
One of the hallmarks of the follicular helper T cell lymphomas a significant degree of post germinal center B cell hyperplasia. We encountered 7 cases of primary cutaneous follicular helper T cell and four cases of AITL, in which the biopsies contained a light chain restricted plasma cell infiltrate in the skin. There were no features that suggested an atypical or more aggressive clinical course in association with the identification of this light chain restricted plasmacytic infiltrates except one case of AITL in whom a diffuse large cell B cell lymphoma subsequently developed.
There was no association with Epstein–Barr virus (EBV) infection light chain restricted plasma cell infiltrate in any of the eleven cases. The basis of these infiltrates is likely a reciprocal functional one reflecting the role of follicular helper T cells in the induction of B cell hyperplasia and the role of plasma cells as a countercheck balance controlling the extent of follicular helper T cell hyperplasia. B cell clonality, plasma cell atypia and blastic B cell transformation can occur without implying a malignant transformation.
•A hallmark of the follicular helper T cell (FHT) lymphomas is a significant degree of post germinal center B cell hyperplasia.•The functional basis is likely reciprocal: The role of FHT cells in the induction of B cell hyperplasia and the role of plasma cells as a countercheck balance affecting the extent of FHT cell hyperplasia.•B cell clonality, plasma cell atypia and blastic B cell transformation can occur without implying a malignant transformation.
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