Disseminated Mucocutaneous Histoplasmosis Diagnosed in the United Kingdom, Presumably as a Result of Recrudescence Decades After Primary Infection Following Immunosuppressive Treatment of Its Mimic, Sarcoidosis: A Multidisciplinary Cautionary Tale.

ABSTRACT: Histoplasmosis is a dimorphic fungal infection, which is rare outside endemic pockets in North, Central, and South America, Asia, and Africa. Herein, we describe a woman in her 80s living in the Scottish Borders region of the United Kingdom with a recent diagnosis of granulomatous rosacea, who on receiving escalating immunosuppression for suspected sarcoidosis, and long-standing rheumatoid arthritis developed a striking eruption involving her eyelids along with painful ulceration of the oral and nasal mucosa. Histopathologic examination of the skin and mucosal lesions demonstrated granulomatous inflammation with numerous yeast forms of fungal organisms with morphological characteristics of Histoplasma species. This was confirmed to be H. capsulatum on fungal culture and direct panfungal polymerase chain reaction assay. Although the patient had not left the United Kingdom for more than 20 years, she gave a travel history involving multiple trips to countries where histoplasmosis is known to occur, before that. This case exemplifies the challenges involved in making a diagnosis of histoplasmosis in nonendemic regions for both clinicians and pathologists alike. In this particular patient, the diagnostic difficulties were compounded by the clinicopathological overlap with other cutaneous and systemic granulomatous disorders like granulomatous rosacea and suspected sarcoidosis and also the exceptionally long latency period between the purported historical primary infection and recent recrudescence. We highlight this unusual case to increase an awareness of histoplasmosis, which is very rare in nonendemic regions like the United Kingdom and involves cases acquired during residence in or travel to endemic areas, to ensure its prompt recognition and treatment.

Inflammatory complications related to tattooing: a histopathological approach based on pattern analysis.

: Although tattooing is an ancient practice, its increasing popularity and social acceptance, variability of tattoo ink composition, sporadic reports of novel tattoo reactions and advances in the field of tattoo removal techniques make it a topic of immense interest among dermatologists and pathologists alike. Since effective legislation governing the tattoo industry is largely lacking in most regions of the world, it is important to recognize the range of tattoo-related complications from a dermatopathological perspective. Using a pattern-based approach, this review details the broad spectrum of inflammatory reactions, which may be encountered in adverse reactions associated with tattooing. Awareness of the range of inflammatory tattoo reactions is crucial as some of these patterns of inflammation can be associated with systemic disorders and others may serve as important clues for an underlying infective condition.

Malignant rhabdoid tumor of the orbit in an infant.

We present the case of an infant with rapidly progressing orbital tumor that had initial radiological and clinical features of both rhabdomyosarcoma and capillary hemangioma. The patient was eventually diagnosed with malignant rhabdoid tumor of the orbit. We discuss the salient histological and radiological features of our case and review the literature on orbital malignant rhabdoid tumors.

Vulval squamous cell cancer - does precursor lesion margin status affect recurrence-free survival after optimal surgical resection for early-stage disease?

OBJECTIVES: Vulval cancer accounts for around 4% of all gynaecological malignancies and most tumours ( > 90%) are of a squamous cell histotype. Most lesions arise on a background of differentiated VIN (dVIN) or lichen sclerosus (LS). Surgical treatment has undergone a paradigm shift with less radical surgery being attempted to preserve vulval structure and function, without compromising oncological outcome. MATERIAL AND METHODS: In this single site retrospective analysis, we consider the data from a tertiary oncology unit, to assess progression-free survival based on the presence of a precursor lesion at the margin of resection.123 patients with FIGO stage 1 vulvar SCC (n = 33 1A, n = 90 1B) were included. RESULTS: One Hundred Five patients (85%) had an associated precursor lesion (dVIN and/or LS). Within the follow-up period, 33 patients (26.8%) had invasive recurrence, of which 24 (72.7%) had surgical resection margins which were positive for a precursor lesion. In patients with an acceptable microscopically clear invasive resection margin of > 2 mm the presence of a precursor lesion at the margin conveyed a higher risk of malignant recurrence when compared to those with completely clear margins (HR = 2.42; 95% CI 1.14-5.16). CONCLUSIONS: This study adds to the available literature emphasising the clinical significance of dVIN or LS at the surgical margin of optimally resected disease. In those who have marginal involvement of a precancerous lesion, increased surveillance should be considered. Future work should explore the need for additional adjuvant therapy in this cohort.

Deep learning-based virtual H& E staining from label-free autofluorescence lifetime images.

Label-free autofluorescence lifetime is a unique feature of the inherent fluorescence signals emitted by natural fluorophores in biological samples. Fluorescence lifetime imaging microscopy (FLIM) can capture these signals enabling comprehensive analyses of biological samples. Despite the fundamental importance and wide application of FLIM in biomedical and clinical sciences, existing methods for analysing FLIM images often struggle to provide rapid and precise interpretations without reliable references, such as histology images, which are usually unavailable alongside FLIM images. To address this issue, we propose a deep learning (DL)-based approach for generating virtual Hematoxylin and Eosin (H&E) staining. By combining an advanced DL model with a contemporary image quality metric, we can generate clinical-grade virtual H&E-stained images from label-free FLIM images acquired on unstained tissue samples. Our experiments also show that the inclusion of lifetime information, an extra dimension beyond intensity, results in more accurate reconstructions of virtual staining when compared to using intensity-only images. This advancement allows for the instant and accurate interpretation of FLIM images at the cellular level without the complexities associated with co-registering FLIM and histology images. Consequently, we are able to identify distinct lifetime signatures of seven different cell types commonly found in the tumour microenvironment, opening up new opportunities towards biomarker-free tissue histology using FLIM across multiple cancer types.

Atypical fibroxanthoma with pseudoangiomatous features: a histological and immunohistochemical mimic of cutaneous angiosarcoma.

Atypical fibroxanthoma and pleomorphic dermal sarcoma may be difficult to separate from cutaneous angiosarcoma. We aim to study the morphological spectrum of pseudoangiomatous features in these tumors and the value of staining for endothelial markers CD31, CD34, FLI1, and ERG. Eleven atypical fibroxanthomas and 3 pleomorphic dermal sarcomas were identified. All tumors arose on sun-damaged skin of elderly men. Atypical fibroxanthomas were nodular and confined to the dermis, whereas pleomorphic dermal sarcoma invaded into underlying fascia. All tumors were composed of pleomorphic epithelioid and spindle cells showing blood-filled spaces and intratumoral hemorrhage. Intracytoplasmic vacuoles (n = 4), hemosiderin deposition (n = 2), and keloidal stromal change (n = 1) were also noted. Immunohistochemically, CD31 was expressed in 43% of cases, FLI1 in 79% and smooth muscle actin in 50%. Staining for CD34, ERG, S100, HMB-45, desmin, p63 and cytokeratins was negative. Follow up (median, 43.1 months; range 1-100), available for 10 patients, showed no adverse outcome. Pseudoangiomatous features and aberrant expression of CD31 and FLI1 in atypical fibroxanthoma and pleomorphic dermal sarcoma may lead to an erroneous diagnosis of cutaneous angiosarcoma. Negativity for CD34 and ERG, in particular, is a reliable differentiating feature in this setting.

Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin.

BACKGROUND: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun-damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. METHODS: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan-A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. RESULTS: All tumors arose on sun-damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan-A and MART-1 was largely limited to tumor giant cells in the absence of S100 or HMB-45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. CONCLUSIONS: Aberrant expression of Melan-A and MART-1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma.

Multifocal Intraretinal Tumour Deposits following Treatment of an Ipsilateral Choroidal Melanoma.

BACKGROUND/AIMS: The aim of this study was to report a patient who, following plaque brachytherapy for a choroidal melanoma, developed two separate retinal foci of malignant melanoma in the same eye, and suggest possible mechanisms that might explain such an occurrence. METHODS: We conducted a retrospective case report. RESULTS: A 79-year-old Caucasian male developed a left inferotemporal choroidal melanoma in 2016 and subsequently underwent ruthenium-106 plaque brachytherapy under the care of the Scottish Ocular Oncology Service. Serial B-scan ultrasonography demonstrated a post-treatment reduction in tumour height to <2 mm. In 2018, 27 months after the treatment, the patient complained of a "black spot" in the centre of his left eye vision. His visual acuity had reduced to counting fingers from 6/24 (corrected Snellen visual acuity). Several new areas of pigmentation and elevation were observed, and uveal melanoma recurrence was initially suspected. Given the multifocal nature of the presentation, the multi-disciplinary team recommended enucleation. Histological examination of the enucleated eye revealed three discrete foci of malignant melanoma - the previously treated choroidal malignant melanoma, and two solitary deposits of malignant melanoma within the retina. CONCLUSION: Retinoinvasive melanoma is a rare subtype of uveal melanoma, characterised by transvitreal melanoma invasion of the retina at a site non-contiguous with the uveal tumour, which may explain the clinical and pathological findings of the reported case.