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1.
Knee Surg Sports Traumatol Arthrosc ; 32(4): 829-842, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38426617

ABSTRACT

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.


Subject(s)
Cartilage, Articular , Mesenchymal Stem Cell Transplantation , Osteoarthritis, Knee , Humans , Hyaline Cartilage , Cartilage, Articular/surgery , Cohort Studies , Prospective Studies , Hyalin , Osteoarthritis, Knee/surgery , Osteotomy/methods , Treatment Outcome , Mesenchymal Stem Cell Transplantation/methods
2.
Neuropathology ; 43(6): 441-456, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37198977

ABSTRACT

Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.


Subject(s)
Drug Resistant Epilepsy , Epilepsy , Child , Adult , Humans , Filamins/metabolism , Hyalin , Brain/pathology , Astrocytes/pathology
3.
Int J Mol Sci ; 24(8)2023 Apr 18.
Article in English | MEDLINE | ID: mdl-37108575

ABSTRACT

The goal of cartilage tissue engineering (CTE) is to regenerate new hyaline cartilage in joints and treat osteoarthritis (OA) using cell-impregnated hydrogel constructs. However, the production of an extracellular matrix (ECM) made of fibrocartilage is a potential outcome within hydrogel constructs when in vivo. Unfortunately, this fibrocartilage ECM has inferior biological and mechanical properties when compared to native hyaline cartilage. It was hypothesized that compressive forces stimulate fibrocartilage development by increasing production of collagen type 1 (Col1), an ECM protein found in fibrocartilage. To test the hypothesis, 3-dimensional (3D)-bioprinted hydrogel constructs were fabricated from alginate hydrogel impregnated with ATDC5 cells (a chondrogenic cell line). A bioreactor was used to simulate different in vivo joint movements by varying the magnitude of compressive strains and compare them with a control group that was not loaded. Chondrogenic differentiation of the cells in loaded and unloaded conditions was confirmed by deposition of cartilage specific molecules including glycosaminoglycans (GAGs) and collagen type 2 (Col2). By performing biochemical assays, the production of GAGs and total collagen was also confirmed, and their contents were quantitated in unloaded and loaded conditions. Furthermore, Col1 vs. Col2 depositions were assessed at different compressive strains, and hyaline-like cartilage vs. fibrocartilage-like ECM production was analyzed to investigate how applied compressive strain affects the type of cartilage formed. These assessments showed that fibrocartilage-like ECM production tended to reduce with increasing compressive strain, though its production peaked at a higher compressive strain. According to these results, the magnitude of applied compressive strain governs the production of hyaline-like cartilage vs. fibrocartilage-like ECM and a high compressive strain stimulates fibrocartilage-like ECM formation rather than hyaline cartilage, which needs to be addressed by CTE approaches.


Subject(s)
Hyaline Cartilage , Hydrogels , Hyaline Cartilage/metabolism , Hydrogels/chemistry , Hyalin/metabolism , Fibrocartilage/metabolism , Extracellular Matrix/metabolism , Collagen/metabolism , Tissue Engineering/methods , Glycosaminoglycans/metabolism , Chondrocytes/metabolism
4.
Int J Obes (Lond) ; 46(5): 1009-1017, 2022 05.
Article in English | MEDLINE | ID: mdl-35082385

ABSTRACT

BACKGROUND: Preliminary data suggested that fat embolism could explain the importance of visceral obesity as a critical determinant of coronavirus disease-2019 (COVID-19). METHODS: We performed a comprehensive histomorphologic analysis of autoptic visceral adipose tissue (VAT), lungs and livers of 19 subjects with COVID-19 (COVID-19+), and 23 people without COVID-19 (controls). Human adipocytes (hMADS) infected with SARS-CoV-2 were also studied. RESULTS: Although there were no between-group differences in body-mass-index and adipocytes size, a higher prevalence of CD68+ macrophages among COVID-19+ VAT was detected (p = 0.005) and accompanied by crown-like structures presence, signs of adipocytes stress and death. Consistently, human adipocytes were successfully infected by SARS-CoV-2 in vitro and displayed lower cell viability. Being VAT inflammation associated with lipids spill-over from dead adipocytes, we studied lipids distribution by ORO. Lipids were observed within lungs and livers interstitial spaces, macrophages, endothelial cells, and vessels lumen, features suggestive of fat embolism syndrome, more prevalent among COVID-19+ (p < 0.001). Notably, signs of fat embolism were more prevalent among people with obesity (p = 0.03) independently of COVID-19 diagnosis, suggesting that such condition may be an obesity complication exacerbated by SARS-CoV-2 infection. Importantly, all infected subjects' lungs presented lipids-rich (ORO+) hyaline membranes, formations associated with COVID-19-related pneumonia, present only in one control patient with non-COVID-19-related pneumonia. Importantly, transition aspects between embolic fat and hyaline membranes were also observed. CONCLUSIONS: This study confirms the lung fat embolism in COVID-19+ patients and describes for the first time novel COVID-19-related features possibly underlying the unfavorable prognosis in people with COVID-19 and obesity.


Subject(s)
COVID-19 , Embolism, Fat , COVID-19/complications , COVID-19 Testing , Endothelial Cells/metabolism , Humans , Hyalin/metabolism , Inflammation/metabolism , Intra-Abdominal Fat/metabolism , Lipids , Lung , Obesity/metabolism , SARS-CoV-2
5.
Microvasc Res ; 142: 104357, 2022 07.
Article in English | MEDLINE | ID: mdl-35283207

ABSTRACT

Blood vessels in lymph nodes (LNs) are unique in comprising both capillaries and high endothelial venules (HEVs). Hyaline vascular type Castleman's disease accompanies robust angiogenesis, but it is unclear how the capillaries and HEVs respond. We retrospectively examined surgical specimens of hyaline vascular type unicentric Castleman's disease patients (n = 24) and control LNs (n = 9). We performed immunohistochemistry of CD 31 for capillaries and MECA-79 for HEVs and calculated their microvascular density. We measured CT enhancement as the ratio of Hounsfield Units (HUs) of the target lesion against muscle compared with microvascular density. The microvascular density of Castleman's disease specimen were (CD 31+) 169.7 ± 77.6, (MECA-79+) 203.5 ± 96.7, and the microvascular density of control LNs were (CD 31+) 80.7 ± 20.1, (MECA-79+) 67.4 ± 23.7, respectively. The microvascular density of both CD 31+ (P < 0.001) and MECA-79+ (P < 0.001) was higher in Castleman's disease. A positive correlation existed between CT HU ratio and microvascular density for both markers (CD 31: r = 0.517, P = 0.002; MECA-79: r = 0.521, P = 0.002). Intra-nodal angiogenesis of Castleman's disease involves robust proliferation of not only CD 31+ capillaries, but also MECA-79+ HVEs, which each correlated with degree of CT enhancement.


Subject(s)
Castleman Disease , Castleman Disease/diagnostic imaging , Castleman Disease/pathology , Castleman Disease/surgery , Humans , Hyalin , Immunohistochemistry , Retrospective Studies , Tomography, X-Ray Computed
6.
Am J Dermatopathol ; 44(4): 291-293, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34783708

ABSTRACT

ABSTRACT: Pulse granulomas are uncommon reactions to vegetable exogenous matter characterized by the presence of hyaline rings. Although they are usually found in the oral cavity or along the gastrointestinal or respiratory tracts, there are a few cases described outside those regions. We present the first case of a granulomatous reaction with hyaline rings in the skin reaction after an accidental wound and suggest the term pulse granuloma-like to describe lesions that resemble pulse granulomas but with no connection to the gastrointestinal or respiratory tracts. Moreover, we provide a graphic comparison of the hyaline rings observed in our case and the histologic sections of some plants that could have been involved.


Subject(s)
Granuloma, Foreign-Body/diagnosis , Hyalin , Wounds, Penetrating , Aged , Diagnosis, Differential , Forearm , Granuloma, Foreign-Body/complications , Granuloma, Foreign-Body/pathology , Humans , Male
7.
Ann Diagn Pathol ; 59: 151948, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35417803

ABSTRACT

We report a case of a 48-year-old female who presented to the emergency department with pelvic/abdominal pain and a recent history of irregular periods. Pelvic ultrasound and computed tomography (CT) scan of the abdomen/pelvis revealed a 7.3 cm adnexal mass with suspicious features. During the intraoperative evaluation, a frozen section slide and a cytological smear were prepared. The cytological preparation was moderately cellular, showing cohesive groups of atypical cells with anisonucleosis, high nuclear to cytoplasmic ratio, and oval nuclei with prominent nucleoli. The tumor cells surrounded extracellular, magenta hyaline globules, forming raspberry bodies. Raspberry bodies are comprised of basement membrane deposits and are a unique finding in ovarian clear cell carcinoma. Raspberry bodies were also found in the frozen section slide, but, in comparison to the cytological preparation, were rare, difficult to identify, and resembled necrotic debris. The intraoperative diagnosis of a clear cell carcinoma is important because the surgical management will be more aggressive, as optimal tumor debulking is shown to have better overall survival. In this manuscript, we detail the intraoperative evaluation of an ovarian mass, the utility of cytological preparation and importance of identifying raspberry bodies in the evaluation of ovarian masses, and surgical management of clear cell carcinoma.


Subject(s)
Adenocarcinoma, Clear Cell , Ovarian Neoplasms , Adenocarcinoma, Clear Cell/diagnosis , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/surgery , Female , Frozen Sections , Humans , Hyalin , Middle Aged , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovary/pathology , Pelvis/pathology
8.
J Hand Surg Am ; 47(2): 195.e1-195.e5, 2022 02.
Article in English | MEDLINE | ID: mdl-33726934

ABSTRACT

Juvenile hyaline fibromatosis is a rare disorder characterized by an extracellular accumulation of hyaline deposit. In the extremities, lesions may remain quiescent or gradually increase in size, eventually resulting in skin ulceration. There is no curative treatment. Surgery may allow some recovery of function, but recurrence is possible. We report a case of juvenile hyaline fibromatosis in both hands of a 25-year-old man who required multiple surgical procedures to address problems with function, pain, and appearance.


Subject(s)
Fibroma , Hyaline Fibromatosis Syndrome , Skin Neoplasms , Adult , Hand/pathology , Hand/surgery , Humans , Hyalin , Hyaline Fibromatosis Syndrome/diagnosis , Hyaline Fibromatosis Syndrome/pathology , Hyaline Fibromatosis Syndrome/surgery , Male , Pain , Upper Extremity/pathology
9.
J Foot Ankle Surg ; 61(4): e9-e14, 2022.
Article in English | MEDLINE | ID: mdl-34801380

ABSTRACT

Posterior ankle impingement syndrome is mainly seen in ballet dancers and frequently associated with specific movements in ballet such as pointe and demi pointe in which the whole-body weight is applied to the maximally plantar flexed ankle. We performed arthroscopic debridement for 2 dedicated ballet dancers on the intervening soft tissue causing posterior ankle impingement syndrome (PAIS). In both cases, T2-weighted magnetic resonance imaging (MRI) revealed low-signal intensity of meniscus-like soft tissue without abnormal osseous findings, connecting from the posterior side of the talus to Kager's fat pad. To examine the intervening soft tissue in detail, we performed histological evaluation by hematoxylin and eosin staining, Safranin O fast green staining, and immunohistochemistry for type I collagen and type II collagen. Hematoxylin and eosin staining showed that there was cartilage-like tissue including chondrocyte-like cells in contact with fibrous tissue. The extracellular matrix in the cartilage zone was consistently stained by Safranin O staining and type II collagen without any staining with type I collagen. These findings suggested that the meniscus-like soft tissue appearing as low-signal intensity on MRI at the posterior side of talus included hyaline-like cartilage. To the extent of our knowledge, these were rare cases of hyaline-like cartilage generation causing PAIS in ballet dancers, which might be associated with ballet specific movements resulting in chondrogenesis.


Subject(s)
Dancing , Joint Diseases , Ankle , Ankle Joint/diagnostic imaging , Ankle Joint/pathology , Collagen Type I , Collagen Type II , Eosine Yellowish-(YS) , Hematoxylin , Humans , Hyalin
10.
Fetal Pediatr Pathol ; 41(3): 464-467, 2022 Jun.
Article in English | MEDLINE | ID: mdl-32969735

ABSTRACT

Background: Choroid plexus carcinoma (CPC) is a predominately pediatric CNS tumor with a variety of histologic features, with hyaline globules only reported once previously. Case report: A two-year-old male child presented with headaches, vomiting, and lower limb weakness. Radiological examination revealed a right temporoparietal intra-axial tumor. On histology, it showed features of CPC containing multiple eosinophilic intracytoplasmic and extracellular hyaline globular structures, which were PAS-positive, diastase resistant, and immunoreactive for alpha-fetoprotein (AFP). Conclusion: CPC can occasionally show AFP immune-positive hyaline globules.


Subject(s)
Carcinoma , Choroid Plexus Neoplasms , Carcinoma/diagnosis , Child , Child, Preschool , Choroid Plexus Neoplasms/diagnosis , Humans , Hyalin , Male , alpha-Fetoproteins
11.
Stomatologiia (Mosk) ; 101(2): 69-73, 2022.
Article in Russian | MEDLINE | ID: mdl-35362706

ABSTRACT

Hyaline juvenile fibromatosis is a rare genetic disease, which is associated with ANTXR2 gene defect. Almost all organs and systems of the body are affected in this pathology. There are clinical symptoms: joint contracture, hyperpigmentation, skin damage like nodules, which can have different sizes, locations and forms, throughout the body, fibromatosis of the gums, internal organs damages (splenomegaly, hepatomegaly, anomalies of the kidneys and other organs), osteoporosis, increased susceptibility to infectious diseases, mental underdevelopment. In this article we describe clinical case of 6-old patient witht hyaline juvenile fibromatosis. The diagnosis was made on the basis of the clinical picture, additional research methods and the results of molecular genetic testing. The patient underwent a number of surgical interventions, histological examination of the surgical material and symptomatic therapy.


Subject(s)
Fibroma , Hyalin , Fibroma/pathology , Humans , Receptors, Peptide
12.
Histopathology ; 78(7): 987-999, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33249657

ABSTRACT

AIMS: In the evolving era of precision medicine, increasing emphasis is placed on detecting molecular alterations driving the development of specific cancers and targeting them with matched therapies that can yield the best outcomes for patients. Lung adenocarcinomas with uncommon actionable alterations, including MET exon 14 skipping (METex14), ERBB2 and BRAF mutations, are rare and poorly characterised cancers. METHODS AND RESULTS: To more clearly understand the histopathological features of lung adenocarcinoma with uncommon actionable alterations, we compared the histological features of 678 cases with mitogenic driver alterations from 996 surgically resected lung adenocarcinomas. Genomic data from our cohort revealed METex14, ERBB2 and BRAF mutations in 13, 16 and 15 cases, respectively. Patients who had lung adenocarcinoma with METex14 were often elderly females. Histological features such as clear cell features (23%), hyaline globules (31%) and nuclear pleomorphism (39%) were the most frequently identified in METex14-positive cases; among those, three cases (23%) had tumour cells with bizarre giant or multilobulated nuclei. Additionally, the micropapillary pattern was the most frequently identified in ERBB2-mutated lung adenocarcinoma (31%). Lung adenocarcinoma with BRAF mutations tended to be less invasive, and the BRAF V600E mutation was identified in only one case with lepidic adenocarcinoma. Immunohistochemically, all METex14, ERBB2 and BRAF-positive tumours, except for invasive mucinous adenocarcinoma, were positive for thyroid transcription factor 1 (TTF-1). CONCLUSIONS: Our data from Japanese patients showed that lung adenocarcinoma with METex14 had unique clinicopathological characteristics: tumour cells with marked nuclear pleomorphism, hyaline globules and expression of TTF-1 in elderly women who never or lightly smoked.


Subject(s)
Adenocarcinoma of Lung , Proto-Oncogene Proteins c-met/genetics , Thyroid Nuclear Factor 1/metabolism , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Aged , Aged, 80 and over , Cohort Studies , Genomics , High-Throughput Nucleotide Sequencing , Humans , Hyalin/cytology , Lung Neoplasms/pathology , Middle Aged , Mutation , Proto-Oncogene Proteins c-met/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Thyroid Nuclear Factor 1/genetics
13.
J Cutan Pathol ; 48(7): 896-901, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33241586

ABSTRACT

Recently, a novel group of CD34+ and S100+ spindle cell tumors with distinctive stromal and perivascular hyalinization showing recurrent gene fusions involving RAF1, BRAF, NTRK1/2/3, and RET has been identified. ALK rearrangements have been rarely reported in this group of tumors. We report a 24-year-old woman with a 1.5-cm pink mass of the scalp. The tumor was made of spindle cells organized in fascicles or haphazardly arranged in a patternless architecture, with areas of stromal and perivascular hyalinization. The tumor cells diffusely expressed CD34 and S100, without SOX-10 expression. The tumor showed diffuse immunopositivity for ALK. RNA sequencing using next-generation sequencing (NGS) detected an EML4-ALK fusion. This case extends the spectrum of this newly described group of CD34+/S100+ spindle cell tumors at the molecular-genetic level. Dermatopathologists should be aware of this recent entity, as it may fall in the differential diagnosis of many other spindle cell tumors with CD34 expression. NGS-based techniques should be performed when facing spindle cell tumors with similar morphology and immunophenotype. Identification of kinase fusions is essential for the precise classification and better knowledge of these tumors, and for targeted therapy in rare aggressive cases.


Subject(s)
Antigens, CD34/metabolism , S100 Proteins/metabolism , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/pathology , Blood Vessels/metabolism , Blood Vessels/pathology , Diagnosis, Differential , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Hyalin/metabolism , Immunohistochemistry/methods , Oncogene Proteins, Fusion , Sequence Analysis, RNA/methods , Soft Tissue Neoplasms/diagnosis , Stromal Cells/metabolism , Stromal Cells/pathology , Treatment Refusal , Young Adult
14.
J Cutan Pathol ; 48(5): 701-705, 2021 May.
Article in English | MEDLINE | ID: mdl-33469928

ABSTRACT

Castleman disease (CD) is an unusual lymphoproliferative disorder characterized by multiple lymphadenopathy accompanied by marked systemic inflammatory symptoms. CD can be unicentric (UCD) or multicentric (MCD), and it can be classified into three types based on histopathology: hyaline vascular type, plasma cell type, and mixed hyaline vascular and plasma cell type. CD involving skin is an unusual clinical manifestation. Abnormalities including rash, hyperpigmentation, cherry hemangiomatosis, paraneoplastic pemphigus, and Kaposi sarcoma have been reported to occur in MCD. Here, we reported an unusual case of MCD which presented initially with disseminated dark brown papules, patches, and plaques, and pathologically demonstrated plasma cell type CD, a finding which is rarely reported. The peculiar clinicopathological features will be discussed.


Subject(s)
Bone Marrow/pathology , Castleman Disease/diagnosis , Lymph Nodes/pathology , Lymphoproliferative Disorders/pathology , Plasma Cells/pathology , Adult , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asian People/ethnology , Biopsy , Castleman Disease/drug therapy , Castleman Disease/pathology , Drug Therapy, Combination , Female , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Hemangioma/pathology , Humans , Hyalin , Hyperpigmentation/pathology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Skin Abnormalities/pathology , Treatment Outcome
15.
Clin Exp Nephrol ; 25(11): 1193-1202, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34115234

ABSTRACT

BACKGROUND: Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients. METHODS: We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients. RESULTS: All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients. CONCLUSIONS: Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Bevacizumab/adverse effects , Capillaries/pathology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Thrombotic Microangiopathies/pathology , Adult , Aged , Aged, 80 and over , Blood Platelets/metabolism , Capillaries/metabolism , Female , Humans , Hyalin/metabolism , Immunoglobulins/metabolism , Integrin beta3/metabolism , Japan , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Glomerulus/blood supply , Male , Middle Aged , Podocytes/metabolism , Proteinuria/etiology , Signal Transduction/drug effects , Thrombotic Microangiopathies/chemically induced , Thrombotic Microangiopathies/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
16.
Oral Dis ; 27(3): 391-403, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31981280

ABSTRACT

Hyaline ring granuloma (HRG) is a rare and atypical foreign-body granulomatous chronic inflammatory condition. Our aim was to make a critical review of the literature cases and also to illustrate histochemical and immunohistochemical findings of a new case. A modified PICO strategy was used. Inclusion criteria were met by case reports and case series with a histologically confirmed diagnosis of HRG, necessarily in mouth or maxillary bones. Exclusion criteria were no access to the full-text paper. The search was done up to 2019, totalizing 231 selected cases in 54 papers. The new case was analyzed through PAS, Azan-Mallory's trichrome, and CD34 and CD68 reactions. HRG is found mainly in the mandible of men, edentulous and prosthesis users, between 51 and 60 years of age, with 0.5-120 months of duration, usually causing edema and pain or discomfort. Endogenous and exogenous theories may be complementary in HRG. Eosinophilic areas could represent particles of vegetal origin, while the hyaline material could be the result of collagen degradation. Considering the material is not always present or even is ring-shaped, we suggest the change from "hyaline ring granuloma" to "granuloma induced by vegetal inoculation."


Subject(s)
Granuloma, Foreign-Body , Hyalin , Child , Child, Preschool , Dentists , Face , Humans , Infant , Infant, Newborn , Male , Mouth
17.
Regul Toxicol Pharmacol ; 127: 105076, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34742868

ABSTRACT

Myrrh is a flavoring agent and food additive. Here, we performed a subchronic toxicity study of Myrrh in male and female F344 rats by feeding at 5,000, 15,000 and 50,000 ppm for 90 days. No deaths or clinical signs were observed. Suppression of body weight gain was observed from the early phase of administration in both males and females in the 50,000 ppm group. Because there were no obvious changes in food intake in any of the Myrrh groups compared with the control group, suppression of body weight gain was considered an adverse effect of Myrrh. Hematology and serum biochemistry parameters with significant changes observed in the Myrrh groups were considered to have no toxicological significance. We observed a significant increase in relative kidney weight in male rats treated with 50,000 ppm Myrrh; this effect was considered to be related to the appearance of hyaline droplets in the epithelium of the proximal tubules histopathologically observed in this group. Immunohistochemical staining with anti-α2u-globulin antibodies suggested that these hyaline droplets were caused by factors other than α2u-globulin deposition. Thus, the no-observed-adverse-effect level of Myrrh was determined to be 15,000 ppm (males: 0.85 g/kg/day, females: 0.95 g/kg/day).


Subject(s)
Commiphora/toxicity , Flavoring Agents/toxicity , No-Observed-Adverse-Effect Level , Resins, Plant/toxicity , Animals , Dose-Response Relationship, Drug , Female , Hyalin/drug effects , Kidney/drug effects , Male , Organ Size/drug effects , Particle Size , Random Allocation , Rats , Rats, Inbred F344
18.
Am J Dermatopathol ; 43(7): 525-529, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-33606370

ABSTRACT

ABSTRACT: Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell carcinoma. In basal cell carcinoma, the presence of intracytoplasmic inclusions is reportedly associated with myoepithelial differentiation. In this regard, EHI has not been conclusively documented in a cutaneous lesion of genuine squamous cell lineage without aberrant differentiation. In the current case, a biopsy from the right thigh of a 71-year-old male patient demonstrated a relatively well-demarcated intraepidermal squamous lesion featured an admixture of predominantly enlarged keratinocytes harboring distinct eccentric intracytoplasmic EHI and a smaller population of keratinocytes displaying pale cytoplasm. Cytologic atypia, mitotic activity, and inflammatory cells were not identified. The intracytoplasmic EHI stained red with Masson's trichrome and were negative with periodic-acid Schiff with and without diastase. Immunologically, the lesion was strongly and diffusely positive for various cytokeratins but negative for ubiquitin and myoepithelial markers. Only cytokeratin AE1 revealed a differential staining pattern as the suprabasal lesional cells displayed significantly stronger immunoreactivity in comparison with the adjacent normal keratinocytes. Polymerase chain reaction for low-risk and high-risk human papillomavirus was negative. Molecular studies did not reveal any mutations commonly encountered in seborrheic or lichenoid keratoses. As an analogous lesion has not previously reported in the literature, the term hyaline inclusion acanthoma is proposed for this peculiar lesion.


Subject(s)
Acanthoma/chemistry , Biomarkers, Tumor/analysis , Hyalin , Keratinocytes/chemistry , Skin Neoplasms/chemistry , Acanthoma/pathology , Aged , Biopsy , Humans , Immunohistochemistry , Keratinocytes/pathology , Male , Skin Neoplasms/pathology
19.
J Eur Acad Dermatol Venereol ; 35(11): 2308-2316, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34331822

ABSTRACT

BACKGROUND: Arteriolosclerotic ulcers of Martorell are histologically characterized by hyaline arteriolosclerosis resulting in concentric occlusion of the arteriolar lumina. Although several authors have previously reported on hyaline changes in hypertensive arteriolopathies, so far, little information is available on the molecular composition of hyaline wall depositions. OBJECTIVES: This study aimed at the molecular characterization of hyaline arteriolar deposits in patients with hypertensive arteriolopathy using confocal Raman spectroscopy. METHODS: Samples of patients diagnosed with arteriolosclerotic ulcers of Martorell were analysed using confocal Raman spectroscopy. The findings were correlated with histological analyses. Skin samples from healthy, non-hypertensive patients served as controls. RESULTS: Confocal Raman spectroscopy analysis revealed that subendothelial hyaline deposits in arteriolosclerotic ulcers are mainly composed of collagen and phospholipids, in particular phosphatidylcholine. The presence of collagen within hyaline deposits was confirmed by Masson's Trichrome and Picrosirius Red staining. Additionally, the presence of collagen could also be shown for hypertensive nephrosclerosis. Actin was markedly decreased in hyalinized compared to control vessels, corresponding to the loss of smooth muscle cells in the process of hyalinization. This was confirmed by immunofluorescence staining for α-smooth muscle actin and desmin. CONCLUSION: The present findings suggest that arteriolar hyaline deposits in hypertensive arteriolopathy are mainly composed of collagen and phospholipids, in particular phosphatidylcholine. Together with the concurrent absence of actin, these findings suggest that potentially critical disease mechanisms involve pressure-induced vascular smooth muscle cell apoptosis with subsequent deposition of collagen.


Subject(s)
Arteriolosclerosis/complications , Collagen/analysis , Hyalin/chemistry , Hypertension/complications , Leg Ulcer/etiology , Phospholipids/analysis , Humans , Spectrum Analysis, Raman
20.
Ann Diagn Pathol ; 51: 151706, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33516059

ABSTRACT

Two cases of primary intrapulmonary hyalinizing spindle cell tumor with giant rosettes are presented. The patients are one woman and one man ages 37 and 42 years respectively. Both patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging revealed the presence of an intrapulmonary mass. One tumor was located in the left lower lobe while the other tumor was in the right upper lobe. Both patients underwent lobectomy. The tumors ranged from 2.4 to 3.0 cm in greatest dimension and were characterized by the presence of a bland spindle cell proliferation with areas of hyalinization and the presence of the so-called giant rosettes. Immunohistochemical stains were performed and the spindle cell component show positive staining for vimentin and negative staining for Bcl-2, CD34, STAT6, p40. Keratin immunohistochemical stain highlighted the entrapped alveolar epithelium while S-100 protein showed weak focal staining in the spindle cells. Both patients have remained alive and well without evidence of recurrence or metastasis for a period of 6 to 14 months post-surgical resection. The cases herein presented highlight the ubiquitous distribution of this tumor and underscores the importance of keeping this particular tumor in the differential diagnosis of spindle cell tumors of the lung.


Subject(s)
Fibroma/diagnosis , Hyalin/metabolism , Lung Neoplasms/pathology , Sarcoma/diagnosis , Adult , Cell Proliferation , Chest Pain/diagnosis , Chest Pain/etiology , Cough/diagnosis , Cough/etiology , Diagnosis, Differential , Dyspnea/diagnosis , Dyspnea/etiology , Female , Fibroma/metabolism , Fibroma/pathology , Fibroma/surgery , Humans , Hyalin/ultrastructure , Immunohistochemistry/methods , Lung Neoplasms/surgery , Male , S100 Proteins/metabolism , Sarcoma/metabolism , Sarcoma/pathology , Sarcoma/surgery , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/surgery , Treatment Outcome , Vimentin/metabolism
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