Tanapox, South Africa, 2022.

Tanapox is a rarely diagnosed zoonosis known to be endemic to equatorial Africa. All previously reported human cases were acquired within 10° north or south of the Equator, most recently 19 years ago. We describe a human case of tanapox in South Africa (24° south of the Equator). Expanded surveillance for this pathogen is warranted.

Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.

Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.

A potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome.

Endometrial carcinoma is the most frequently occurring female genital tract malignancy in developed nations, with a rising annual incidence. Endometrioid endometrial carcinoma (EEC), the most common histological variant, differs in morphologic and molecular characteristics from serous carcinomas but morphological distinction of high-grade EECs from serous carcinomas may prove difficult. Thus, molecular categorization of tumors may allow for better tumor classification with greater insight into the underlying biology of endometrial carcinomas with new therapeutic options. Microsatellite instability (MSI) is a commonly occurring molecular aberration in EECs and has been identified in most Lynch Syndrome (LS) associated tumors. This tumor syndrome predisposes afflicted individuals to a myriad of tumors including endometrial carcinoma. Herein, the molecular signature of endometrial tumors as well as LS, and its clinical manifestations are reviewed. Understanding of the pathogenetic pathways allows for greater comprehension of occurrences at a molecular level which are then appreciated at a cellular and tissue level, by the histopathologist. The molecular classification of endometrial tumors allows for further targeted therapeutic options for affected patients. Screening tests for patients with suspected LS enables surveillance of other tumors in the affected patient and her family with the potential to decrease morbidity and mortality. It is envisioned that this overview will allow for enhanced comprehension of genetic pathways by practicing pathologists, oncologists, gynecologists and other members of the multidisciplinary team, all of whom are involved in the management of the patient with an endometrial malignancy.

A presumptive case of cutaneous emergomycosis in a female patient with HIV - Maseru, Lesotho.

Emergomycosis is a recently described emerging opportunistic fungal infection among individuals living with HIV, in whom it is a cause of significant mortality and morbidity. This article retrospectively reports on a presumptive case of extensive cutaneous emergomycosis in a young immunocompromised patient from Lesotho. The histopathological features on skin biopsy were in keeping with emergomyces infection. The lesions responded to treatment with amphotericin B and oral fluconazole. Contribution: This case contributes to the existing evidence that as an emergent opportunistic infection, emergomycosis is possibly widespread in Africa but the true extend of the disease is not fully defined. This is further aggravated by the diagnostic difficulty as a result of limited resources in some areas in the region.

Endemic mycoses in South Africa, 2010-2020: A decade-long description of laboratory-diagnosed cases and prospects for the future.

BACKGROUND: Emergomycosis, histoplasmosis, sporotrichosis and blastomycosis are endemic to southern Africa; the first two are AIDS-related mycoses. We described laboratory-diagnosed cases of endemic and imported mycoses in South Africa over a decade and discuss available diagnostic tools, reasons for the current under-estimation of cases and future strategies to improve case ascertainment. MATERIALS AND METHODS: We analysed electronic pathology laboratory data from all public laboratories and one large private laboratory in South Africa from 2010-2020. Diagnostic specimens processed at the national mycology reference laboratory were also included. We classified cases as proven, probable and possible based on the method of identification. RESULTS: We identified 682 cases, of which 307 were proven, 279 were probable and 96 were possible. Of 307 culture-confirmed cases, 168 were identified by phenotypic methods plus sequencing, 128 by phenotypic methods alone and 11 by direct PCR. Of 279 probable cases, 176 had yeasts observed on histology, 100 had a positive Histoplasma antigen test and 3 a positive pan-dimorphic PCR test. All 96 possible cases had compatible clinical syndrome with inflammatory infiltrates on skin tissue histology. A majority of cases had an unspecified endemic mycosis (207/682, 30.4%), followed by sporotrichosis (170/682, 24.9%), emergomycosis (154/682, 22.6%), histoplasmosis (133/682, 19.5%), blastomycosis (14/682, 2.1%) and talaromycosis (4/682, 0.6%). CONCLUSIONS: This study reports a relatively low number of cases over a decade considering an estimated large population at risk, suggesting that a substantial fraction of cases may remain undiagnosed. There is a need to increase awareness among healthcare workers and to develop rapid point-of-care diagnostic tools and make these widely accessible.

Clinical Improvement of Disseminated Acanthamoeba Infection in a Patient with Advanced HIV Using a Non-Miltefosine-Based Treatment Regimen in a Low-Resource Setting.

Disseminated Acanthamoeba species infection is likely an underrecognized and underdiagnosed opportunistic infection in patients with advanced human immunodeficiency virus (HIV) disease in South Africa. It presents a unique clinical challenge in that the diagnosis can be difficult to establish and management options are limited in low-resource settings. To our knowledge, there is a paucity of literature to date on the successful use of combination treatment options for patients in low-resource settings without access to miltefosine. We present a case describing the clinical improvement of disseminated Acanthamoeba infection in a patient with advanced HIV using a non-miltefosine-based treatment regimen. The case serves to highlight that Acanthamoeba sp. infection should be considered as a differential diagnosis for nodular and ulcerative cutaneous lesions in patients with advanced HIV in South Africa, and that although there are alternative options for combination treatment in countries without access to miltefosine, efforts should be made to advocate for better access to miltefosine for the treatment of acanthamoebiasis in South Africa.

Cutaneous mixed tumor, eccrine variant: a clinicopathologic and immunohistochemical study of 50 cases, with emphasis on unusual histopathologic features.

Mixed tumor, eccrine type, is a rare cutaneous adnexal neoplasm, mostly reported as isolated case reports. A systematic analysis of its histopathologic and immunohistochemical features has not previously been performed on a large series. The purpose of our investigation was to study a large number of cutaneous eccrine mixed tumors so as to fully characterize the entire spectrum of changes in the epithelial and stromal components, with an emphasis on unusual histopathologic features that may represent a diagnostic pitfall. This article reports a light microscopic and immunohistochemical study of 50 cases of eccrine mixed tumor, complemented by a literature review. Our study identified some unusual histopathologic features, thus extending the morphologic spectrum of this neoplasm. These included prominent cribriform areas, clear cell change, pseudorosette structures, prominent osseous metaplasia, and physaliphorous-like cells. Most of these features have not been previously recorded in eccrine mixed tumors and may represent a potential diagnostic pitfall.

Segmental lichen aureus: a report of two cases treated with methylprednisolone aceponate.

Two cases of segmental lichen aureus with a response to topical 0.1% methylprednisolone aceponate ointment are reported. A 9-year-old child and a 23-year-old man showed complete resolution of their lesions following treatment with the latter after 7 months and 4 months, respectively. Lichen aureus is a rare form of the pigmented purpuric dermatoses characterized by golden-brown and lichenoid macules and papules, most often on the lower extremities. Segmental presentations have seldom been described. Histology showed a lichenoid infiltrate with extravasation of red blood cells and haemosiderin deposition. The aetiology is unclear and treatment is disappointing. We report an uncommon segmental presentation of lichen aureus with resolution of the lesions after treatment with a topical corticosteroid.