Still Far to Go With Characterisation of Molecular and Genetic Features of Diffuse Large B-Cell Lymphoma in People Living With HIV: A Scoping Review.

Diffuse large B-cell lymphoma (DLBCL) accounts for half of non-Hodgkin lymphoma cases in people living with human immunodeficiency syndrome (PLWH). The interplay of viremia, immune dysregulation and co-infection with oncogenic viruses play a role in pathogenesis of DLBCL in PLWH (HIV-DLBCL). This scoping review aimed to describe the molecular landscape of HIV-DLBCL, investigate the impact of biomarker on clinical outcomes and describe technologies used to characterise HIV-DLBCL. Thirty-two papers published between 2001 and 2023 were included in this review. Samples of HIV-DLBCL were relatively small (16-110). Cohort effects influenced frequencies of molecular characteristics hence their impact on survival was not clear. Molecular features were distinct from HIV-unrelated DLBCL. The most frequently assessed characteristic was cell of origin (81.3% of studies). Somatic mutations were the least researched (6.3% of studies). Overall, biomarker identification in HIV-DLBCL requires broader richer data from larger or pooled samples using more powerful techniques such as next-generation sequencing.

Histological and scanning electron microscope observations on the developing retina of the cuttlefish (Sepia officinalis Linnaeus, 1758).

In this work we present a detailed study of the major events during retinal histogenesis of the cuttlefish Sepia officinalis from early embryos to newly hatched animals and juveniles. For this purpose, we carried out morphometric and histological analyses using light and scanning electron microscopy. From St19, the first embryonic stage analysed, to St23/24 the embryonic retina is composed of a pseudostratified epithelium showing abundant mitotic figures in the more internal surface. At St24 the first photoreceptor nuclei appear in the presumptive inner segment layer, while an incipient layer of apical processes of the future rhabdomeric layer become visible at St25. From this stage onwards, both the rhabdomeric layer and the inner segment layer increase in size until postnatal ages. In contrast, the width of the supporting cell layer progressively decreases from St25/26 until postnatal ages. S. officinalis embryos hatched in a morphologically advanced state, showing a differentiated retina even in the last stages of the embryonic period. However, features of immaturity are still observable in the retinal tissue during the first postnatal weeks of life, such as the existence of mitotic figures in the apical region of the supporting cell layer and migrating nuclei of differentiating photoreceptors crossing the basal membrane to reach their final location in the inner segment layer. Therefore, postnatal retinal neurogenesis is present in juvenile specimens of S. officinalis.

Adenomatoid odontogenic tumor: A histopathologic profile of 43 cases with evidence supporting a mixed odontogenic origin.

BACKGROUND: Adenomatoid Odontogenic Tumor (AOT) accounts for 3% of all odontogenic tumors. It has been classified by WHO as an odontogenic tumor of purely epithelial origin. The current study attempts to establish the origin of the tumor along with detailed histopathological and clinicoradiographic analysis of 43 cases of AOT. MATERIAL AND METHODS: Forty-three cases were reviewed from the departmental archives for demographic data, radiographic features and histological features. Further, histopathological slides were stained with Picrosirius Red (PSR) and observed under polarised light. RESULTS: A majority of the cases were seen in the anterior jaws (76.7%), and were less than 3 cms (76.7%) in greatest dimension. Equal number of cases were of follicular and extra-follicular location while one was peripheral. Predominantly solid histological pattern was noted in 53.5%. Varied sub-patterns were observed with most cases exhibiting solid nodules and strands of tumor cells. Few cases showed melanin pigmentation. Over a third of cases (37.2%) showed dentigerous cyst like areas and one case each showed features of ossifying fibroma and focal cemento-osseous dysplasia. Tumor droplets, hyaline rings within duct-like structures, dentinoid material and osteodentin showed reddish yellow birefringence when observed under polarised microscopy post PSR staining. CONCLUSION: This study highlights the diverse histopathological variation of AOT with evidence to reclassify it as a mixed odontogenic tumor based on the polarising microscopic findings with PSR staining.

Navigating the Diagnosis and Treatment of Astroblastoma: A Pediatric Case Report.

Astroblastoma, a rare glial tumor of the central nervous system, presents diagnostic and therapeutic challenges due to its low incidence and variable clinical presentations. In this case study, we present the case of an 11-year-old boy with high-grade astroblastoma, highlighting the complexities in diagnosis and treatment. The clinical presentation initially involved right-sided motor weakness, which, after undergoing a brain MRI, revealed a large solid cystic mass in the left parietal lobe. Histopathological examination after undergoing surgery confirmed an astroblastoma with high-grade features, characterized by increased cellularity and high mitotic activity. Immunostaining patterns supported the glial origin of the tumor. Gross total resection remains the primary approach for its treatment, but adjuvant therapies for high-grade astroblastomas are still evolving, offering potential life-changing possibilities for the future. Due to its rarity, collecting sufficient data to develop an effective treatment protocol for this uncommon tumor is very challenging. This case underscores the importance of combined efforts and ongoing research to effectively navigate the diagnosis and treatment of astroblastoma.

The developmental architecture of the crop of quail embryos (Coturnix coturnix): Morphometric, light and scanning electron microscopy.

The present study focused on the histogenesis of the crop in quail embryos. The developmental sequence was recorded from day 10 of incubation to the hatching day (17th day) by gross anatomy, morphometric analysis and by using light and scanning electron microscope (SEM). Grossly, the crop was distinguished as an enlarged pouch of the cervical oesophagus on the 12th day of incubation. Histologically, the development of the crop began on the 10th day of incubation. The muscularis mucosae was observed as a small, thin layer of myoblast cells on the 10th day, then it appeared as longitudinally arranged smooth muscle fibres with progression of the developmental age till hatching day. The submucosal layer was also observed on the 10th day, while the lamina propria, muscular layer (inner circular and outer longitudinal layers of smooth muscle fibre) and glandular primordia were detected on the 12th day. The epithelial cells of crop revealed affinity for PAS stain and AB-PAS on the 10th day of incubation till the 17th day, while the affinity for AB stain appeared on the 14th day of incubation. Additionally, the glandular cells showed the positive for AB, PAS and AB-PAS on the 12th day of incubation. SEM sections showed variable sizes of the openings of the oesophageal glands. In conclusion, the present study provided a detailed overview of the histogenesis of the crop in quail embryos.

Histomorphogenesis of sublingual salivary gland of Indian sheep.

The primordial anlage of sublingual gland was first noticed as a solid epithelial bud from oral epithelium at the 24th day of foetal development. The terminal buds were arranged in the form of clusters with undifferentiated epithelial cells and terminated in a bulb-like structure in the 30-day-old sheep foetus. On the 37th day, lumenization and branching of the main cord was noticed. The primary septa were observed from the 55th day onwards which resulted in the formation of lobulation on the 60th day. The capsule formation was initiated by aggregation of mesenchymal tissue on the 63rd day. On the 100th day, terminal tubules differentiated to form secretory end pieces. Tubular portions formed intercalated and striated ducts. Predominantly mucous type of acinar cells was seen from the 110th day onwards with myoepithelial cells. The number of lobules increased with increase in parenchyma from 130th day onwards. Micrometrical studies revealed that the mean diameter of acini, intercalated, striated and large ducts was increased with advancement of age and significant differences were observed between groups. Localization of acidic and neutral mucopolysaccharides were observed in mucous and goblet cells. Fine lipid droplets were observed in intralobular and interlobular connective tissue however, phospholipids were observed in cell membrane of acini and ducts. The current investigation provides microstructural standards for the organogenesis of the sublingual gland of miniature sheep and can lay the foundation for further studies in the morphological investigation of salivary gland development.

Articulated lengthening fixation apparatus (ALFA) for the management of gap non-union of distal femur: Initial experience on a new technique.

Purpose: Distal femur non-union is difficult to deal with because of limited or no bone stock left for holding pins. Also, knee range of motion is a major concern in case of distal femur non-union to deal with. ALFA is a new modality of definitive external fixator with limited literatures. This paper aims to present the series of cases of gap non-union of the distal femur managed with an ALFA fixator and their outcome as an initial experience on a new device. Methods: Eight patients of gap non-union distal femurs where the ALFA fixator application was done between January 2022 to June 2022 were evaluated. Patients with intra-operative bone gap <5 cm were acutely docked and >5 cm were left as it is as a bon gap and gradual distraction was done to achieve bone gap length and limb length discrepancy. Patients were assessed for functional, radiological, and clinical outcomes, at the time of surgery, completion of distraction, and completion of consolidation. The scores from our study were compared with the Ilizarov and mono-lateral fixator with the available data. Results: Eight patients managed with ALFA fixator had mean age of 32.12 ± 6.82 years. The mean limb length discrepancy at the time of operation was 5.25 ± 3.11 cm, with Intra-operative bone gap of 4.68 ± 3.47 cm where 5 patients managed with acute docking and 3 patient managed with leaving the bone-gap. The mean regenerate gained after distraction was 9 ± 4.63 cm at the mean distraction duration of 113.37 ± 67.34 days. The mean time of removal of the fixator (n = 5), was 203 ± 111 days, and the mean external fixator index, days/cm (n = 5) was 34 days/cm. The number of complications per patient was 0.25 per patient. The Mean residual LLD was, 0.43 ± 0.58, with significant improvement of Limb Length compared to pre-operative LLD with a p-value of 0.0014. Conclusion: ALFA fixator for gap non-union as an alternative to Ilizarov, and LRS provides adequate distraction osteogenesis, less neurovascular complication due to pins, better patient tolerability, and user-friendly distraction of the distal femur with preserved knee range of motion. Level of evidence: III.

Ilizarov Ring Fixator in the Lower Limb for 2000 Days: A Case Report.

Ring external fixators developed by Gavriil Abramovich Ilizarov from Russia are used to treat the difficult cases of infected non-union, shortening of limbs by bone lengthening, and deformity correction in joints and bones in isolation or in combination. Fixation of the involved bone with the ring is commonly achieved using four rings, each having two Ilizarov wires that are passed along the superior surface of the ring, then across the bone, and exiting out on the opposite side touching the surface of the ring. The case report herein reports a patient who kept the ring fixator on his thigh without any problem for a long period of five and a half years. The case is being reported due to the abnormally long period of ring fixator application without any complications and the excellent result achieved in terms of union and infection control.

Ocular and extraocular sebaceous carcinomas: A retrospective study with emphasis on the presence of in situ lesion and discussion and review of the histogenesis of extraocular sebaceous carcinoma.

Sebaceous carcinoma (SC) is a rare carcinoma classified as ocular or extraocular. Ocular SC is believed to arise from the meibomian glands or the glands of Zeis. However, the origin of extraocular SC is controversial because there is no evidence of carcinoma arising from pre-existing sebaceous glands. Several hypotheses about the origin of extraocular SC have been proposed, including one suggesting an origin from intraepidermal neoplastic cells. Although extraocular SCs have been shown to occasionally comprise intraepidermal neoplastic cells, no study has investigated whether intraepidermal neoplastic cells possess sebaceous differentiation. The present study analyzed the clinicopathological features of ocular and extraocular SC, with an emphasis on the presence of in situ (intraepithelial) lesions. It retrospectively reviewed the clinicopathological features of eight patients with ocular and three patients with extraocular SC (eight women and three men; median age, 72 years), respectively. In situ (intraepithelial) lesions were observed in four of the eight ocular SC cases and one of the three extraocular SC cases and an apocrine component was noted in one patient with ocular SC (seboapocrine carcinoma). In addition, immunohistochemical analyses showed that the androgen receptor (AR) was expressed in all ocular SCs and two of the three extraocular SC cases. Adipophilin expression was observed in all ocular and extraocular SC. In situ lesions of extraocular SC showed positive immunoreactivity for both AR and adipophilin. The present study is the first to demonstrate sebaceous differentiation in in situ lesions of extraocular SC. The possible origin of extraocular SC is speculated to be the progenitor cells present in the sebaceous duct or interfollicular epidermis. The results of the present study and reported cases of SC in situ indicate that extraocular SC also arises from intraepidermal neoplastic cells.

Acute shortening and angulation for complex open fractures: an updated perspective.

Reestablishing an intact, healthy soft tissue envelope is a critical step in managing lower extremity injuries, particularly high-grade open tibia fractures. Acute shortening and angulation can be used independently or together to address complex soft tissue injuries, particularly when bone loss is present. These techniques facilitate management of difficult wounds and can be combined with local soft tissue rearrangement or pedicled flaps as needed, avoiding the need for free tissue transfer. After angular deformity correction, adjacent bone loss can be addressed with bone grafting or distraction histogenesis. This article discusses the indications for, surgical technique for, and limitations of acute shortening and angulation for management of open lower extremity fractures.

Central Granular Cell Odontogenic Tumor: A Literature Review of Cases Reported in the Last 71 Years with a New Case Report.

Central granular cell odontogenic tumors (CGCOTs) are rare, benign, slowly growing odontogenic neoplasms. Due to their uncertain histogenesis, CGCOTs are still not included as a distinct entity in the WHO classification (2017) of odontogenic tumors. We report a case of CGCOT involving the right side of maxillary anterior region of a 39-year-old white female. Immunohistochemical staining showed that granular cells positively expressed CD68 and vimentin, and negatively expressed S-100 protein. Meanwhile, we searched PubMed, Google Scholar, and Scopus databases to summary the clinico-pathological features of 51 reported cases of CGCOT. The results showed that the granular cells of 28.6% cases were immunopositive for vimentin and CD68, and odontogenic epithelial cells were positive immunoreactivity for cytokeratin. These findings reinforced the mesenchymal origin of granular cells and the odontogenic nature of epithelium islands.

Case report: Composite mantle cell lymphoma and classical Hodgkin lymphoma.

Composite mantle cell lymphoma and classical Hodgkin lymphoma is very rare and the actual origin of it is still unclear. Here we reported a new case of composite mantle cell lymphoma and classical Hodgkin lymphoma and analyzed its molecular changes. Eight mutations were identified in its Hodgkin component through next-generation sequencing. In addition, we reviewed the published cases of composite mantle cell lymphoma and classical Hodgkin lymphoma and summarized the molecular changes of reported cases as well as the current case to explore the possible pathway of histogenesis.

Isolation of a Population of Cells Co-Expressing Markers of Embryonic Stem Cells and Mesenchymal Stem Cells from the Rudimentary Uterine Horn of a Patient with Uterine Aplasia.

More than 50% cells isolated from the endometrial cavity scraping and the myometrium of the rudimentary horn of an underdeveloped uterus removed from a patient with uterine aplasia and maintained under culturing conditions normal for mesenchymal stem cells (MSC) expressed embryonic transcription factors Oct4 and Nanog, embryonic cell membrane sialyl glycolipid SSEA4, and MSC markers. After 2-3 passages, the cells lost the expression of the early embryogenesis markers, but retained MSC markers. The presence of dormant stem cells in the underdeveloped endometrium and in the uterus indicates that this tissue has a regenerative potential that can be activated and used for completion of organ morphogenesis. This task requires the development of methods of early diagnosis of morphogenesis impairment and tools for safe reactivation of the ontogenesis.

Age-related glomerular histogenesis in inbred indigenous rabbit (Oryctolagus cuniculus): A morphological, morphometrical, and immunohistochemical study with emphasis on Lgr5-positive cells.

Although the regeneration of renal glomeruli and nephrons after injuries especially in adult mammals is not possible, understanding normal glomerular histogenesis is important. Here, we sought to study the morphometrical and histological development of the normal renal glomeruli of rabbits from birth until postnatal day 40. Moreover, we immunohistochemically evaluated the extent and rate of the Lgr5 expression in the immature renal stem/progenitor cells. The untreated, clinically healthy inbred indigenous rabbits (from Duhok city of Iraqi Kurdistan) were sacrificed at postnatal days 1, 10, 15, 30, and 40. After being processed and embedded in paraffin, rabbit anti-human Lgr5 as a primary antibody and rabbit ImmunoCruz LSAB as a staining kit were used for the immunohistochemical detection of Lgr5+ve cells. For normal histology, hematoxylin and eosin were used. The peak generation and regression of renal corpuscles were at postnatal days 10, and 40, respectively, with 50% decrease. The glomeruli diameter significantly increased (1.3-fold, p = 0.001), whereas the Bowman's space diameter decreased (50%, p < 0.0001) from postnatal day 1-40. The immature nephrons were seen only in one-day postnatal rabbits. While the superficial glomeruli were compact and small, the juxtamedullary glomeruli were larger and segmented. The formation and development of the juxtaglomerular apparatus were documented at postnatal days 30 and 40 only. Our data revealed highly expressed Lgr5 protein at postnatal day one, and the expression level decreased gradually with advancing age. It was moderately expressed on day 10 and mildly expressed on day 15, whereas no expression was recorded on days 30 and 40 postnatally. Our study provides evidence that the Lgr5 gene, within multipotent stem cells and their lineage progeny, was activated within newly formed glomeruli throughout the early postnatal stages of nephrogenesis.

Histogenesis of intracranial germ cell tumors: primordial germ cell vs. embryonic stem cell.

INTRODUCTION: Intracranial germ cell tumor (iGCT) is a rare disorder and often occurs during childhood and adolescence. iGCTs are frequently localized in pineal region and hypothalamic-neurohypophyseal axis (HNA). In spite of well-established clinical and pathological entity, histogenesis of iGCTs remains unsettled. Current theories of histogenesis of iGCTs include germ cell theory (from primordial germ cells (PGCs) of aberrant migration) and stem cell theory (transformed embryonic stem (ES) cells). In order to comprehend the histogenesis, we revisit the origin, migration, and fate of the human PGCs, and their transformation processes to iGCT. DISCUSSION: In "germ cell theory," transformation of ectopic PGCs to iGCT is complex and involves multiple transcription factors. Germinoma is derived from ectopic PGCs and is considered a prototype of all GCTs. Non-germinomatous germ cell tumors (NGGCTs) develop from more differentiated counterparts of embryonic and extra-embryonic tissues. However, there is a distinct genomic/epigenomic landscape between germinoma and NGGCT. ES cells transformed from ectopic PGCs through molecular dysregulation or de-differentiation may become the source of iGCT. "Stem cell theory" is transformation of endogenous ES cells or primitive neural stem cell to iGCTs. It supports histological diversity of NGGCTs because of ES cell's pluripotency. However, neural stem cells are abundantly present along the subependymal zone; therefore, it does not explain why iGCTs almost exclusively occur in pineal and HNA locations. Also, the vast difference of methylation status between germinoma and NGGCT makes it difficult to theorize all iGCTs derive from the common cellular linage. CONCLUSION: Transformation of PGCs to ES cells is the most logical mechanism for histogenesis of iGCT. However, its detail remains an enigma and needs further investigations.

Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors).

Cribriform morular thyroid carcinoma (CMTC) is a rare malignant thyroid tumor with a peculiar growth pattern secondary to permanent activation of the WNT/ß-catenin pathway. CMTC may be associated with familial adenomatous polyposis or sporadic; it shares morphological features with papillary thyroid carcinoma (PTC) and was considered a variant of PTC in the 2017 WHO classification of tumors of endocrine organs. The new 5th edition of the WHO classification of endocrine and neuroendocrine tumors considered CMTC an independent thyroid neoplasm of uncertain histogenesis. A thymic/ultimobranchial pouch-related differentiation in CMTC has been recently postulated. We, however, have used the pathological and immunohistochemical features of this case of CMTC with 2 novel oncogenic somatic variants (c.3428_3429insA, p.(Tyr1143Ter) and c.3565del, p. (Ser1189Hisfs*76) of the APC gene to propose an origin from follicular cells (or their endodermal precursors). As usual in CMTC, the morular component of this tumor was positive for CDX2. Given the fact that WNT/ß-catenin signaling, through CDX2, activates large intestine and small intestine gene expression, we postulate that in CMTC, the tumor cells have their terminal differentiation blocked, thus showing a peculiar primitive endodermal (intestinal-like) phenotype negative for sodium-iodide symporter, thyroperoxidase, and thyroglobulin. Establishing the histogenesis of CMTC is very relevant for the development of appropriate therapies of redifferentiation, particularly in patients where the tumor cannot be controlled by surgery.

Staged Ilizarov distraction histogenesis and corrective reconstruction for severe malunited calcaneal fractures.

PURPOSE: Severe calcaneal malunion is a clinical conundrum for the difficulty of calcaneal reconstruction without soft tissue complications. The aim of this study is to introduce the treatment strategy and preliminary results of staged Illizarov distraction histogenesis and corrective reconstruction for severe malunion of calcaneal fractures. METHODS: From June 2014 to May 2020, 14 patients with severe calcaneal malunion treated with the staged strategy were retrospectively analyzed. At the first stage, calcaneal osteotomy and external fixation with Ilizarov frame were performed. The restoration of the approximate configuration of calcaneus and the expansion of contractural soft tissue were achieved by gradual calcaneal distraction. At the second stage, corrective reconstruction was performed and autogenous iliac crest bone graft was used. Clinical and radiographic outcomes were evaluated at final follow-up. RESULTS: The average time of Ilizarov distraction and total fixation was 21.4 days and 41.0 days at first-stage treatment. At a mean follow-up of 33.1 months, the average American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score increased significantly from 24.0 to 72.4 (p < 0.01). And the mean visual analogue scale (VAS) score had improved remarkably from 8.2 to 2.4 (p < 0.01). Radiographs showed that talocalcaneal height, calcaneal width, calcaneal tuberosity height, hindfoot alignment angle, and talar declination angle were improved to a great extent (p < 0.01). Only one patient had minor pin site infection at first-stage treatment and one got superficial wound infection after second-stage surgery. No wound dehiscence, skin necrosis, or deep infection occurred. CONCLUSION: Staged Ilizarov distraction histogenesis and corrective reconstruction is a safe and effective treatment strategy for reducing soft tissue complications and improving reconstruction results in surgical correction of severe calcaneal malunion.

Olfactory Neuroblastoma: Morphological Reappraisal and Molecular Insights with Quantum Leap in Clinical Perspectives.

PURPOSE OF REVIEW: The purpose of review is to provide a comprehensive review of the literature focusing on the recent advances in the diagnosis, molecular underpinning, and targeted therapy of olfactory neuroblastoma (ONB). RECENT FINDINGS: Studies focused on the molecular fingerprinting of ONB are critical to engage new promising treatment strategies. Molecular-based subtype classifications have been proposed (basal-like ONB and neural-like ONB) but are not widely used. The rationale for implementation of DNA methylation analysis and IDH2 sequencing in routine work-up for ONB is gaining recognition. Expression of somatostatin receptors (SSTR) in ONB open new avenues for both, diagnostic (especially metastatic disease) and new treatment protocols with somatostatin analogs. Olfactory carcinoma is proposed as a unifying diagnostic terminology pertinent to epithelial divergent differentiation in olfactory neuroblastoma. Molecular (genetic and epigenetic) efforts on olfactory neuroblastoma are promising; however further refinement is needed for employment of these biomarkers as clinical standard of care. Ongoing and future multi-institutional collaborative studies will contribute to further understanding of ONB biology and aid the development of targeted treatments for this disease.

Central Granular Cell Odontogenic Tumor: A Literature Review of Cases Reported in the Last 71 Years with a New Case Report / 中国医学科学杂志(英文版)

Central granular cell odontogenic tumors (CGCOTs) are rare, benign, slowly growing odontogenic neoplasms. Due to their uncertain histogenesis, CGCOTs are still not included as a distinct entity in the WHO classification (2017) of odontogenic tumors. We report a case of CGCOT involving the right side of maxillary anterior region of a 39-year-old white female. Immunohistochemical staining showed that granular cells positively expressed CD68 and vimentin, and negatively expressed S-100 protein. Meanwhile, we searched PubMed, Google Scholar, and Scopus databases to summary the clinico-pathological features of 51 reported cases of CGCOT. The results showed that the granular cells of 28.6% cases were immunopositive for vimentin and CD68, and odontogenic epithelial cells were positive immunoreactivity for cytokeratin. These findings reinforced the mesenchymal origin of granular cells and the odontogenic nature of epithelium islands.