Folliculotropic mycosis fungoides associated with follicular mucinosis: A case report and mini review.

Key Clinical Message: F-MF is a rare non-classic variant of MF. In the case of hair loss, this should be a diagnostic consideration. The essence of the diagnosis of F-MF is a careful medical history, physical examination, and a combination of immunohistological and molecular analyses (Cureus. 2022; 14:e21231, Ann Saudi Med. 2012; 32:283, Oman Med J. 2012; 27:134, Int J Dermatol. 2016; 55:1396, Saudi Med J. 2018; 39:994 and Case Rep Oncol. 2018; 11:436). Abstract: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with multiple subtypes. Follicular MF (F-MF) is a non-classic variant of MF. Histological features entail folliculotropism and damage of the epithelium lining of the hair follicles with or without mucin deposition. A 52-year-old male patient complained of recurrent skin lesions on the scalp over 8 months. The lesions appeared suddenly, enlarged over time, and became itchy. A skin punch biopsy was performed. Histological features included mucin deposits in the epithelium of the hair follicles and dense, predominantly perifollicular atypical lymphocytes infiltrating the follicular epithelium. The lymphoid cells were composed of CD3-positive T cells (CD4/CD8-positive T cells) with a shift in favor of the former. The case was diagnosed as F-MF on an immunohistological basis. The diagnosis of F-MF is often difficult for dermatologists and dermatopathologists alike. Not only clinicopathological correlations but also immunohistochemical and molecular analysis are required.

Cutaneous Malignant Melanoma Presenting as an Isolated Splenic Metastasis: An Update.

Although the spleen is a highly vascularized organ, metastatic deposits from non-hematolymphoid solid malignancies are rare. This is reasoned to the inherent resistance of the splenic parenchyma to harbor metastases. The splenic capsule, lack of afferent lymphatics, contractile properties of the spleen, and the angular and gyroid course of the splenic artery form several barriers against the metastatic spread of malignant tumors. Moreover, the immune cells in the white and red pulps of the spleen have strong defensive ability against the tumor cells. Metastasis from solid tumors to the spleen often occurs only during widespread distant spread. Malignant melanoma is a rare but fatal malignancy. Isolated splenic metastasis from malignant melanoma is exceptionally rare. Studies that addressed the splenic metastasis from cutaneous malignant melanoma are scarce. This minireview was performed to address this subject. Here we present an overview of the clinicopathologic features of isolated splenic metastatic melanoma. The diagnostic biochemical markers in melanoma are also discussed.

Dermatofibromas with Aberrant Expression of CD34 Protein: A Systematic Review and a Reappraisal of Clinicopathological Features and Histogenesis.

BACKGROUND: Dermatofibromas (DFs) are benign fibrohistiocytic lesions that usually do not express CD34 protein. This study aimed to analyze the literature concerning the immunohistological and ultrastructural features of DFs. It also related these features to the histogenesis of these lesions. METHODS: This study included a PubMed literature search for studies addressing the clinicopathological, ultrastructural, and immunohistochemical features of DFs. It also presented some current cases of CD34-negative DFs and a subset of these lesions with aberrant expression of this protein. RESULTS: Analysis of the PubMed literature revealed that DFs with an aberrant expression of CD34 are rare tumors that commonly affect the extremities of adult females. Separating these tumors from dermatofibrosarcoma protuberans (DFSP, CD34-positive tumors) requires using a large panel of immunostains. Ultrastructurally, DFs are composed of diverse cell types, including cells with histiocytic, myofibroblastic, and fibroblastic features. An analysis of the DFs described by this study revealed that cases with an aberrant expression of CD34 protein had slightly high mean age and male sex predominance when compared to CD34-negative cases. The former commonly affected the extremities. There was no evidence of local recurrence or distant metastasis on follow-up. CONCLUSIONS: DFs have the potential to express CD34 protein, defining a rare aberrant phenotype, which was not associated with any differences in the outcome as compared to CD34-negative DFs.

Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels.

Pentameric ligand-gated ion channels (pLGICs) play a leading role in synaptic communication, are implicated in a variety of neurological processes, and are important targets for the treatment of neurological and neuromuscular disorders. Endogenous lipids and lipophilic compounds are potent modulators of pLGIC function and may help shape synaptic communication. Increasing structural and biophysical data reveal sites for lipid binding to pLGICs. Here, we update our evolving understanding of pLGIC-lipid interactions highlighting newly identified modes of lipid binding along with the mechanistic understanding derived from the new structural data.

Picky ABCG5/G8 and promiscuous ABCG2 - a tale of fatty diets and drug toxicity.

Structural data on ABCG5/G8 and ABCG2 reveal a unique molecular architecture for subfamily G ATP-binding cassette (ABCG) transporters and disclose putative substrate-binding sites. ABCG5/G8 and ABCG2 appear to use several unique structural motifs to execute transport, including the triple helical bundles, the membrane-embedded polar relay, the re-entry helices, and a hydrophobic valve. Interestingly, ABCG2 shows extreme substrate promiscuity, whereas ABCG5/G8 transports only sterol molecules. ABCG2 structures suggest a large internal cavity, serving as a binding region for substrates and inhibitors, while mutational and pharmacological analyses support the notion of multiple binding sites. By contrast, ABCG5/G8 shows a collapsed cavity of insufficient size to hold substrates. Indeed, mutational analyses indicate a sterol-binding site at the hydrophobic interface between the transporter and the lipid bilayer. In this review, we highlight key differences and similarities between ABCG2 and ABCG5/G8 structures. We further discuss the relevance of distinct and shared structural features in the context of their physiological functions. Finally, we elaborate on how ABCG2 and ABCG5/G8 could pave the way for studies on other ABCG transporters.

ABCG5/G8: a structural view to pathophysiology of the hepatobiliary cholesterol secretion.

The ABCG5/G8 heterodimer is the primary neutral sterol transporter in hepatobiliary and transintestinal cholesterol excretion. Inactivating mutations on either the ABCG5 or ABCG8 subunit cause Sitosterolemia, a rare genetic disorder. In 2016, a crystal structure of human ABCG5/G8 in an apo state showed the first structural information on ATP-binding cassette (ABC) sterol transporters and revealed several structural features that were observed for the first time. Over the past decade, several missense variants of ABCG5/G8 have been associated with non-Sitosterolemia lipid phenotypes. In this review, we summarize recent pathophysiological and structural findings of ABCG5/G8, interpret the structure-function relationship in disease-causing variants and describe the available evidence that allows us to build a mechanistic view of ABCG5/G8-mediated sterol transport.