Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held

The calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence indicates the importance of PNNs in synaptic transmission at the calyx of Held. Previously, a unique differential expression of aggrecan and brevican has been reported at this calyceal synapse. However, the role of hyaluronan and proteoglycan binding link proteins (HAPLNs) in PNN formation and synaptic transmission at this synapse remains elusive. This study aimed to assess immunohistochemical evidence for the effect of HAPLN4 on differential PNN formation at the calyx of Held. Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both gene knockout (KO) and wild-type (WT) mice. An in situ proximity ligation assay demonstrated the molecular association of brevican with HAPLN4 in WT and HAPLN1 in gene KO mice. Further elucidation of the roles of HAPLN4 may highlight the developmental and physiological importance of PNN formation in the calyx of Held.

Extra-pelvic endometriosis presenting as recurrent hepatic cyst: case report and literature review

Hepatic endometriosis is a very rare form of endometriosis first described by Rokitansky in 1986. To our knowledge, 42 cases of hepatic endometriosis have been reported in the literature till date. The condition offers a diagnostic challenge owing to its variable presentation on imaging and the need for histological and immunohistochemical evidence for a definite diagnosis. We hereby present the 43rd case of ectopic endometrium in the liver of a 30 years old, multiparous female who presented with fever and pain in the right hypochondrium. Radiological imaging suggested a cystic lesion which was managed laparoscopically. Histopathology and immunohistochemistry findings came out to be consistent with endometriosis. The case highlighted the importance of considering endometriosis as a differential in all women irrespective of age and previous history of endometriosis.

First Immunohistochemical Evidence of Human Tendon Repair Following Stem Cell Injection: A Case Report and Review of Literature

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

Genomic and Metabolic Hallmarks of SDH- and FH-Deficient Renal Cell Carcinomas

Purpose: Succinate dehydrogenase-deficient and fumarate hydratase-deficient renal cell carcinomas (SDHRCC and FHRCC) are rare kidney cancers driven by loss of metabolically proximal enzymes. We sought to define and compare the genomic and metabolomic hallmarks of these entities. Experimental Design: We analyzed SDHRCC and FHRCC tumors with either immunohistochemical evidence of loss of protein expression or genomically-confirmed biallelic inactivation of SDHA/B/C/D/AF2 or FH. Somatic alterations were identified using clinical pipelines, and allele-specific copy number changes were identified using FACETS. Mass-spectrometry-based metabolomic profiling was performed on available SDHRCC and FHRCC tumors. Results: Forty two patients were analyzed (25 FHRCC, 17 SDHRCC). In the germline analysis, 16/17 SDHRCC harbored a germline alteration in SDHB, whereas only 17/22 FHRCC had pathogenic germline FH variants. SDHRCC had a lower mutation burden (p = 0.02) and copy number alteration burden (p = 0.0002) than FHRCC. All SDHRCC presented with deletion of chromosome 1p (overlapping SDHB), whereas FHRCC demonstrated high but not ubiquitous loss of 1q (FH locus). Both SDHRCC and FHRCC demonstrated significant, idiopathic accumulation of the metabolite guanine. FHRCC tumors had elevated levels of urea cycle metabolites (argininosuccinate, citrulline, and fumarate), whereas SDHRCC had elevation of numerous acylcarnitines. These characteristic metabolic changes enabled the identification of a previously unrecognized SDH-deficient RCC. All data is available at http://private.cbioportal.org/ Conclusion: Despite sharing similar genetic etiology, SDHRCC and FHRCC represent distinct molecular entities with unique genetic and metabolic abnormalities.

Adamantinoma-like variant of Ewing sarcoma in the metatarsal bone after chemotherapy: Report of a case successfully treated with a pedicled osteocutaneous fibular transfer

Adamantinoma-like Ewing sarcoma is a rare variant of Ewing sarcoma known to have histologic and immunohistochemical evidence of squamous differentiation. This variant most commonly occurs in the head and neck region with a few cases reported in long bones of the limbs. It may be associated with poorer clinical outcome and could pose a diagnostic challenge(s) particularly if it occurs in older patients or as a metastatic lesion. We present a case of Ewing sarcoma in the metatarsal of an 11 year old boy that manifested adamantinoma-like morphology after neo-adjuvant chemotherapy. Chemotherapy has been reported to induce neuronal maturation and rhabdoid morphology in cases of Ewing sarcoma, but no reports of treatment induced squamous differentiation with P40/P63 expression have been demonstrated. This is also the first documented case to use a pedicled osteocutaneous fibular transfer in a metatarsal malignancy, which is usually treated by either ray or below knee amputation.

Inflammatory Skin Lesions in Three SARS-CoV-2 Swab-Negative Adolescents: A Possible COVID-19 Sneaky Manifestation?

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with various clinical manifestations, including skin lesions. In particular, during the COVID-19 pandemic lock-down period numerous chilblain-like lesions, mainly located on the feet, were observed in adolescents. The latter were often asymptomatic or associated with very mild respiratory symptoms. Here, we report three cases of acral nodular lesions in SARS-CoV-2 swab-negative adolescents with histological findings of chronic immune-mediated inflammation and immunohistochemical evidence of SARS-CoV-2 spike glycoproteins in endothelial cells and eccrine sweat glands. In one of these cases, the virus presence was confirmed by electron microscopy.