Five paediatric patients with mycosis fungoides and our approach to provide age-appropriate information and psychological support.

Cutaneous lymphoproliferative diseases in childhood are rare and they are clinically and pathologically heterogeneous, which makes their diagnosis challenging. Although there is limited long-term data and guidance on management, evidence suggests these to be different conditions from cutaneous lymphoma in adults, highlighting the need for age-appropriate patient information. We present clinical outcomes for our paediatric cohort of five patients with mycosis fungoides, emphasizing that despite diagnostic delays, mycosis fungoides in this age group tends to yield a good prognosis. It remains uncommon to provide clinical expertise together with psychological support in a dermatology paediatric service. Here, we provide our experience in offering this combined service. In conjunction with these patients, we have co-produced an accessible patient information leaflet targeted at a younger audience for support and to clarify potential misconceptions from a diagnosis of cutaneous lymphoma.

Patterns of Mucin Deposition in Lichen Planopilaris: A Journey From Follicular "Bubbles" to Perifollicular Fibroplasia.

ABSTRACT: Lichen Planopiolaris (LPP) is a scarring alopecia characterised by a perifollicular lymphoid cell infiltrate at the level of the infundibulum and isthmus. While perifollicular mucinous fibroplasia is an established finding in LPP, intrafollicular mucin deposition has not been previously reported. We describe two cases with this histopathology and suggest it may represent a helpful clue to the diagnosis of LPP, in the appropriate clinical setting.

Skin-Limited, Methotrexate-Associated Epstein-Barr Virus-Positive Mucocutaneous Ulcer-A Mimicker of High-Grade Lymphoma. A Report of 4 Cases and Review of the Literature.

ABSTRACT: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein-Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy.

Cutaneous Epstein-Barr virus-associated smooth muscle tumor in immunosuppression.

A 36-year-old renal transplant recipient presented 15 months post-transplantation with a cutaneous spindle cell neoplasm with features of smooth muscle differentiation treated with local excision. 1.4 years later, a magnetic resonance imaging liver scan with gadolinium demonstrated multiple bilobar enhancing hepatic lesions, in keeping with metastases. A core biopsy revealed morphological appearances similar to the previous cutaneous spindle cell neoplasm. Epstein-Barr virus early RNA (EBER) in situ hybridization demonstrated strong diffuse staining of both cutaneous and liver tumor cells for EBER indicative of Epstein-Barr virus (EBV) infection. This is a rare presentation of multifocal EBV-associated smooth muscle tumors first presenting in the skin in an adult renal transplant recipient, which, despite being multifocal and involving the liver, may confer a better prognosis than predicted.

The Spectrum of Cutaneous Reactive Angiomatoses in End Stage Renal Failure.

ABSTRACT: Cutaneous reactive angiomatoses encompass a spectrum of conditions driven by underlying occlusive vasculopathy. We present 2 cases of reactive angioproliferation in the context of end-stage renal failure (ESRF) manifesting as painful cutaneous ulceration. The first case demonstrates histologic features of diffuse dermal angiomatosis. The second case illustrates a nonspecific pattern of vascular proliferation which does not conform to any of the classically described subtypes, therefore reinforcing the concept of a spectrum of histopathologic changes in reactive angioproliferations. Diffuse dermal angiomatosis has been described in ESRF alone and in association with calciphylaxis, a life-threatening condition. Recognizing the patterns of reactive angioproliferation in the context of ESRF therefore has clinical relevance. Earlier identification may facilitate mitigation of risk factors and improve prognosis.

Cutaneous intravascular epithelioid hemangioma. A clinicopathological and molecular study of 21 cases.

Pure intravascular growth of epithelioid hemangioma (EH) is exceptional. Herein, we report a series of 21 intravascular EHs, representing a potential serious diagnostic pitfall by mimicking malignant vascular neoplsms with epithelioid morphology. The tumors developed in 12 males and 4 females, aged from 11 to 71 years (mean age 40.2 years) with a predilection for the extremities (13 of 21, 61.9%), followed by the head and neck (8 of 21, 38.1%). Lesions ranged in size from 2 to 30 mm (mean size 13 mm). The most common presenting feature was a slowly growing nodule. Most neoplasms were solitary (13 of 16 patients, 81.2%) but three patients developed more than one intravascular EH (3 of 16, 18.8%). Treatment consisted of complete surgical excision and was generally curative. Follow-up was available for 13 lesions that had developed in ten patients (range 4-72 months, mean 27.3 months). No recurrences or development of additional tumors were observed. All 21 lesions developed in subcutaneous veins. Two morphological patterns of intravascular epithelioid endothelial cell proliferation were observed: (1) a lobular capillary hemangioma-like proliferation with variable formation of open vascular lumina and (2) a solid proliferation generally lacking open vascular spaces. A lobular capillary hemangioma-like pattern was the sole pattern in nine lesions, a mixed lobular hemangioma-like pattern, and solid pattern in eight and a pure solid pattern in four intravascular EHs. Mitotic activity in epithelioid endothelial cells ranged from 0 to 7 mitoses per 10 high-power field (mean 2.1 mitoses per 10 HPFs). Six lesions displayed brisk mitotic activity of five or more mitoses per 10 HPF (6 of 21, 28.5%). The number of mitoses was usually more prominent in areas with solid growth. Atypical mitoses were not observed. No intratumoral necroses were seen. Cytological atypia was mild (20 out of 21 cases). By immunohistochemistry, all tumors were positive for CD31 (14 out of 14) and ERG (5 out of 5). While all tested cases were FOS negative by immunohistochemistry (6 out of 6), one out of six cases (case 6) displayed FOSB nuclear positivity in about 30% of the lesional endothelial cells. Eight cases were analysed by FISH for the presence of FOS and FOSB gene rearrangements. While all cases were negative for FOSB rearrangements, a single case proved positive for FOS gene break-apart. In conclusion, intravascular growth of EH is not associated with adverse biological behavior. Solid intravascular proliferations of endothelial cells can mimic a malignant vascular tumor with epithelioid morphology. Nevertheless, intravascular EHs display mild cytological atypia coupled with low mitotic activity, and a lack of atypical mitoses, pronounced nuclear atypia, multilayering or tumor necrosis. Finally, the FOS gene is infrequently rearranged, and there are no FOSB gene abnormalities in this subset of EHs, suggesting a potential distinct pathogenesis than most classic EHs.

Expanding the clinical spectrum of dermal hyperneury: report of nine new cases and a review of the literature.

AIMS: Dermal hyperneury is defined as the hypertrophy of small nerves in the dermis. It has been described in a variety of settings. We present a series of nine new cases with a distinctive clinical presentation and review the existing literature. The aim of the study was to summarise the clinical, histopathological and immunohistochemical findings in a case series of dermal hyperneury with unique clinical presentation. METHODS AND RESULTS: Nine cases were identified from the referral practice of one of the authors. Clinical characteristics, including demographic details, were collated. The histopathological features and novel immunohistochemical findings were analysed. Four cases presented with multiple skin lesions. Clinical evaluation revealed no associated syndromic stigmata. The histology in all cases was that of dermal hyperneury. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and RET was supportive of the lack of syndromic association. CONCLUSION: The presentation of dermal hyperneury with multiple cutaneous lesions and no syndromic associations is distinctive, and no study with PTEN and RET immunohistochemistry has previously been reported. Comparisons with recent reports of multiple non-syndromic mucocutaneous neuromas are discussed.

Epstein-Barr Virus-Induced Cutaneous Diffuse Large B-Cell Lymphoma in a Patient With Angioimmunoblastic T-Cell Lymphoma.

Cutaneous manifestations of Epstein-Barr virus (EBV)-driven B-cell lymphoid proliferations occur rarely as a result of severe immunodeficiency. To date, only a few cases of extranodal EBV-associated B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported, and less common is a cutaneous presentation. AITL is a rare aggressive tumor that carries a poor prognosis and prompt diagnosis, and recognition of EBV-associated diffuse B-cell lymphoma is essential in these patients to instigate the correct treatment.

Poroid hidradenoma in the hand: A case report and systematic review.

Poroid hidradenoma (PH) is a rare benign neoplasm of the skin appendages. There are currently no guidelines for its management, and little information available regarding the natural history, treatment options, or outcomes. Systematic literature review identified 19 cases of isolated PH. Mean age at presentation was 54 years. Male to female ratio was 3:1, and the majority of cases were in the head and neck region. One-third of lesions were painful or tender. Sizes varied from 0.11 × 0.9 × 0.2 cm (digit) to 6 cm (presternal region). Twelve cases were treated by surgical excision, while the remainder were biopsy specimens. Follow-up was reported in five cases, with a median follow-up of 1 year. No cases of local invasion or spread have been reported, although there was one case of possible recurrence identified 8 years after surgical excision. The presented case is the first to identify a PH on the hand, represents the smallest lesion to date, and was successfully treated by excision. We suggest that PHs be treated by excision and followed up for 6 to 12 months. Given one case of potential (but unconfirmed) recurrence, and no report of malignant transformation, we suggest that narrow margins may be appropriate.

Cutaneous PEComa: a rare entity to consider in an unusual site.

PEComa is a mesenchymal neoplasm thought to derive from the perivascular epithelioid cell, a hypothetical cell type not yet identified. PEComa is a broad term that was recently expanded to include visceral, retroperitoneal, and somatic soft tissue, in addition to cutaneous tumors, which share morphological and immunohistochemical features in common with angiomyolipoma, lymphangiomyomatosis, and clear cell "sugar" tumor. The latter have distinct, site-related, clinical, morphological, and biological features. PEComas share features of concurrent melanocytic and myocytic differentiation. Most cases are sporadic, but renal and pulmonary PEComas can be part of the tuberous sclerosis syndrome more often than PEComas from other sites. We report a case of cutaneous PEComa to raise awareness of the entity occurring at this site and caution against misinterpretation as a primary or metastatic malignancy, for example melanoma or renal cell carcinoma, clear cell type.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Heterologous osteosarcomatous and rhabdomyosarcomatous elements in dedifferentiated solitary fibrous tumor: further support for the concept of dedifferentiation in solitary fibrous tumor.

Dedifferentiation within solitary fibrous tumor is a rare and only recently characterized phenomenon. It differs from malignant solitary fibrous tumor in that there is abrupt transition between classical solitary fibrous tumor and the dedifferentiated component. The latter is a high-grade sarcoma, which can exhibit a number of morphologies, but heterologous differentiation is exceptionally rare. We report a case of dedifferentiated solitary fibrous tumor, with heterologous osteosarcomatous and rhabdomyosarcomatous elements, arising in the deep soft tissue of the thigh of a 59-year-old man. This comprised morphologically and immunohistochemically typical solitary fibrous tumor, juxtaposed to pleomorphic, high-grade malignant neoplasm of 2 distinct lineages. The sharp demarcation between well-differentiated and dedifferentiated components is typical of the dedifferentiation seen in other mesenchymal neoplasms. This expands the range of histopathology of this rare, newly characterized type of malignant progression in solitary fibrous tumor.

The role of hair follicle counts and ratios in the histopathological assessment of androgenic alopecia, alopecia areata and telogen effluvium: does counting 'count'?

The histopathological assessment of scalp biopsies for the diagnosis of alopecia is most commonly undertaken in specialist centers. Occasionally, pathologists encounter such specimens outside a specialist setting or at a low frequency, which makes a confident diagnosis difficult. A methodical approach is essential to identify and interpret the histopathological findings, and one of the diagnostic tools is the use of follicular counts and ratios. This method is particularly emphasized in the context of non-scarring alopecia and, furthermore, for the identification of alopecias with overlapping features. We raised the question as to what is the role of follicular hair counts and ratios in the differential diagnosis of non-scarring alopecia with overlapping features, and sought the answer in our literature review. The English literature on the histopathological assessment of horizontal scalp biopsies taken for the evaluation of non-scarring alopecia, focusing on hair follicle counting as a diagnostic tool, with particular emphasis on androgenetic alopecia, alopecia areata, and telogen effluvium, was reviewed. Follicular counts and ratios are a helpful diagnostic tool. However, these need to be coupled with the morphological features specific for each alopecia subtype to render a confident diagnosis.

Myxoinflammatory fibroblastic sarcoma: morphologic and genetic updates.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a malignant mesenchymal neoplasm most frequently arising in the distal extremities of adults, which usually behaves in a low-grade manner but is capable of metastasizing to local and distant sites, rarely leading to death. It is a rare tumor whose unusual morphology can lead to erroneous histologic diagnosis, either as a nonneoplastic (infectious or inflammatory) process or as a variety of neoplastic diseases. While its exact origin is uncertain, ultrastructural studies have shown at least some of the constituent cells to be modified fibroblasts. Distinct and reproducible genetic abnormalities identified in MIFS are translocation t(1;10)(p22:q24), with rearrangements of the TGFBR3 and MGEA5 genes associated with increased levels of FGF8, and formation of marker/ring chromosome 3, with amplification of the VGLL3 locus. Because these genetic abnormalities are shared by both MIFS and hemosiderotic fibrohistiocytic lipomatous tumor, it is thought that these 2 morphologically distinct neoplasms may comprise a spectrum of disease defined by these genetics. We review the literature on MIFS and discuss morphology (including that of MIFS/hemosiderotic fibrohistiocytic lipomatous tumor hybrid lesions), immunohistochemistry, the differential diagnosis, and recent molecular genetic developments.