Histological Pattern Research Articles

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti–CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed (“inside-out” (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.

Prevalence of Enteric Infections in Patients on Immune Checkpoint Inhibitors and Impact on Management and Outcomes.

Stool pathogen testing is recommended as part of the initial evaluation for patients with new-onset diarrhea on immune checkpoint inhibitors (ICIs), yet its significance has not been well-studied. We aimed to determine the impact of multiplex gastrointestinal (GI) pathogen PCR testing on the clinical course and use of immunosuppressive therapy in patients who develop diarrhea on ICIs. This retrospective cohort included individuals who underwent GI pathogen panel PCR for diarrhea on ICIs at Memorial Sloan Kettering between 7/2015 and 7/2021. The primary outcome was use of immunosuppressive therapy for suspected immunotherapy-related enterocolitis (irEC). Secondary outcomes included diarrhea severity and endoscopic and histologic disease patterns. Among 521 ICI-treated patients tested for GI pathogens, 61 (11.7%) had a positive PCR. Compared to patients without detectable infections, patients with infections had more frequent grades 3-4 diarrhea (37.7% vs. 19.6%, P < .01) and colitis (39.3% vs. 14.7%, P < .01). However, patients with infections did not have higher rates of persistent or recurrent diarrhea and were less likely to receive steroids (P < .01) and second-line immunosuppressive agents (P = .03). In 105 patients with lower endoscopy, similar trends were observed and no differences in endoscopic severity or histologic patterns were noted between groups. GI infections in ICI-treated patients presenting with diarrhea are linked to more severe but self-limited clinical presentations and may be optimally treated with observation and supportive care alone. Routine and timely stool pathogen testing may help avert unnecessary empiric immunosuppression for suspected irEC, which has been linked to blunted antitumor responses and numerous adverse effects.

James Walker Dawson: His fingers and their historical context

Multiple Sclerosis (MS) is one of the most prevalent neurologic disorders in the world. James Walker Dawson examined, in considerable depth, the gross and histologic patterns of MS. Today, periventricular plaques that exhibit an appearance typical for demyelination are nicknamed “Dawson’s Fingers.” A literature review was conducted on PubMed and Google Scholar to find articles that chronicle the personal and professional life of James Walker Dawson. Research focused on Dawson’s work with disseminated sclerosis, or MS as it is known today. Born in India, Dawson and his family moved to Scotland as a child, and he studied at the Edinburgh Institution. After earning his medical degree, Dawson started his career at the Royal College of Physicians of Edinburgh. While his early career focused on the study of wound healing and inflammation, Dawson transitioned into neurologic research under the guidance of Dr. Alexander Bruce in 1908. Dawson’s landmark manuscript, “The Histology of Disseminated Sclerosis,” published in 1916, featured findings from extensive research on the pathology of MS in nine patients. His findings earned him recognition as a founder of autoimmune neurology and foremost contributor to the current understanding of MS.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-yearOS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-yearprogression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats

Myocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse effects. Consequently, the development of new therapeutic agents with a reduced adverse event profile is necessary. In this regard, 2-methoxyestradiol (2ME), the metabolic end-product of oestradiol, possesses anti-inflammatory and antioxidant properties. The aim of this research is to assess the impact of 2ME on cardiac injury caused by isoproterenol (ISO) in rats. Animals were separated into six groups; controls, and those receiving 2ME (1 mg/kg), ISO (85 mg/kg), ISO + 2ME (0.25 mg/kg), ISO + 2ME (0.5 mg/kg), and ISO + 2ME (1 mg/kg). 2ME significantly attenuated ISO-induced changes in electrocardiographic changes and the cardiac histological pattern. This compound also decreased lactate dehydrogenase activity, creatine kinase myocardial band and troponin levels. The ability of 2ME to act as an antioxidant was shown by a decrease in malondialdehyde concentration, and the restoration of glutathione levels and superoxide dismutase activity. Additionally, 2ME antagonized inflammation and cardiac cell apoptosis, a process determined to be mediated, at least partially, by suppression of Gal-3/TLR4/MyD88/NF-κB signaling pathway. 2ME offers protection against acute ISO-induced MI in rats and offers a novel therapeutic management option.

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer

BackgroundThe presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. ObjectiveTo assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. Design, setting, and participantsPatients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. Outcome measurements and statistical analysisWe used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. Results and limitationsOf the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36–49%) for detection of cribriform morphology and 44.1% (95% CI 36–52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47–58%). Among patients who underwent multiparametric magnetic resonance imaging–guided biopsies, the sensitivity was 54% (95% CI 39–68%) for detection of cribriform morphology and 37% (95% CI 19–58%) for detection of IDC. ConclusionsBiopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. Patient summaryProstate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.

P03.05.B PRIMARY GAMMA KNIFE RADIOSURGERY FOR PINEAL REGION TUMORS, A SYSTEMATIC REVIEW AND POOLED ANALYSIS OF AVAILABLE LITERATURE WITH HISTOLOGICAL STRATIFICATION

Abstract BACKGROUND Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality following surgery or as a salvage treatment at recurrence. We aimed to gather the existing evidence on the topic and analyze single-patient level data to address the efficacy and safety of primary GKSR when only a biopsy was attempted or biochemical or neuroimaging diagnosis was available. MATERIAL AND METHODS This is a systematic review of literature (Pubmed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers in our final analysis comprising 64 patients. Additional 12 patients were included from the authors’ original series. RESULTS A total of 76 patients reached the final analysis. Presumptive diagnoses included intrinsic pineal low-grade (46%), glial low-grade (LGG, 5%), pineoblastoma (4%), germ cell tumors (GCTs, 4%), pineal tumors of intermediate differentiation (3%), other pineal tumors (3%), glial high-grade (HGG, 2%) and meningioma (1%). In 32% of cases, the diagnosis was unclear. Only 57% of cases received histological confirmation. The mean age at treatment was 38.7y and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose (50% isodose) of 14.7 ± 2.1 Gy. At a median 36mo follow-up, local control was achieved in 84% of cases. Ten patients showed progression within a mean time of 24.2mo. Progression was more common in HGG and GCTs (p=0.03) compared to intrinsic pineal tumors. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3y-OS was 100% for LGG, 90% for the intrinsic pineal, 60% for GCTs, 50% for HHG, and 82% for undetermined tumors. The 3y-PFS was 100% for LGG, 90% for the intrinsic pineal, 32% for GCTs, and 0% for HHG. Median PFS was 5mo for HHG and 34mo for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as presenting symptom strongly predicted mortality (OR 104, p=0.02), while GCTs and HHG histology well predicted PD (OR: 13, p=0.04). CONCLUSION These results support the efficacy and safety of primary GKSR treatment of pineal region tumors. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Paradoxical psoriasis: The flip side of idiopathic psoriasis or an autocephalous reversible drug reaction?

Psoriasis is a common, chronic skin disease that results mainly from the complex interplay between T cells, dendritic cells, and inflammatory cytokines including TNF-α, IL-17, IL-12, and IL-23. Successful therapy with anti-cytokine antibodies has proved the importance of these key cytokines, especially TNF-α. During the anti-TNF-α treatment of classical idiopathic psoriasis, a small portion of patients develop new psoriasiform lesions. This contradictory phenomenon was named paradoxical psoriasis which resembles idiopathic psoriasis clinically but presents overlapped histological patterns and distinct immunological processes. In this review, we discuss the differences between idiopathic psoriasis and paradoxical psoriasis with an emphasis on their innate immunity, as it is predominant in paradoxical psoriasis which exhibits type I IFN-mediated immunity without the activation of autoreactive T cells and memory T cells. We also put up an instructive algorithm for the management of paradoxical psoriasis. The decision on drug discontinuation or switching of biologics should be made based on the condition of underlying diseases and the severity of lesions.

Pathological Spectrum of Ovine Pulmonary Adenocarcinoma in Small Ruminants: A Focus on the Mixed Form.

Ovine pulmonary adenocarcinoma (OPA) is a contagious respiratory tumor of small ruminants, manifesting in chronic weight loss and respiratory failure. Infection with the betaretrovirus jaagsiekte sheep retrovirus (JSRV) is the cause of OPA. Here, we describe the gross and microscopic features of twenty-six sheep and one goat with naturally occurring JSRV-associated OPA. All the animals included in this study had pulmonary lesions morphologically consistent with OPA, but the majority of the observed lesions demonstrated features of both the classical and the atypical form of OPA, and were, therefore, classified grossly as mixed. The gross lesions were located mainly in the cranial pulmonary lobes, were multifocal to coalescing, variable in number and size, flat to slightly raised, firm, and white to grey. Histologically, the cases were classified according to the predominant architectural patterns as lepidic, papillary, acinar, or mixed; the mixed histological pattern was the most prevalent. The aim of this study was to describe the gross and microscopic spectrum of OPA in naturally infected small ruminants from Spain. The mixed form of OPA is less commonly reported, and can be confused with other concurrent pulmonary pathologies (such as BALT hyperplasia in SRLV-associated pneumonia or lungworm granulomas).

Idiopathic Lichenoid and Granulomatous Vulvitis: A Distinct Clinicopathological Entity.

The combination of lichenoid and granulomatous inflammation is uncommon in vulval biopsies. We present a series of 5 patients with lichenoid and granulomatous vulvitis, presenting with clinical changes resembling lichen sclerosus. Despite detailed clinicopathological investigation and follow-up, there was no apparent association with an underlying recognized cause. All 5 cases occurred in postmenopausal women and displayed a distinctive histological pattern of superficial band-like inflammation with granulomas "anchored" to the dermoepidermal junction. There was no evidence of deeper granulomatous inflammation. Despite repeated biopsies over 2 years in 2 patients, neither developed typical histological features of lichen sclerosus. We postulate that idiopathic lichenoid and granulomatous vulvitis may represent a distinct clinicopathologically defined vulvar dermatosis.

T1a Renal Cell Carcinoma With Metastasis: Japanese Society of Renal Cancer Retrospective Multi-institute Results.

Small renal cell carcinomas (sRCC) have drastically increased in recent years. Considering that sRCC have heterogeneous biology, it would be clinically relevant if specific clinical or pathological parameters could predict sRCC metastasis. In the present study, we aimed to assess the clinicopathological factors of pathologic T1a RCC (pT1a RCC) with or without metastasis to explore factors predicting metastasis. The present study included 198 patients with pT1a RCC who underwent radical or partial nephrectomy at fifteen institutions belonging to the Japanese Society of Renal Cancer, between1985 and 2017. Clinicopathological parameters, including age, sex, tumour size, tumour side, histological subtype, histological nuclear grade, lymphovascular invasion, and histological growth patterns, were analysed. Fuhrman grade 3 or 4 tumours and infiltrative tumour growth patterns were significantly higher in patients with metastasis than in those without. The most common site of synchronous metastasis was the bone in patients with pT1a RCC (65.4%), whereas for patients with post-surgery metachronous metastasis (46.2%), it was the lungs. Histological growth pattern and nuclear grade are vital for predicting metastasis in pT1a RCC, suggesting careful long-term follow-up for such patients.

Histological Patterns of Steroid Resistant Nephrotic Syndrome in Bulgarian Children: a Single Centre Study

Nephrotic syndrome is the most frequent glomerular disease in childhood. Steroid resistant nephrotic syndrome (SRNS) represents about 20% of children with nephrotic syndrome. SRNS is one of the leading indications for performing renal biopsy in children. The objective of this retrospective study is to determine the histological patterns of SRNS in Bulgarian children and to compare them with the worldwide findings. The study included 49 patients with SRNS. All biopsies were performed at the Department of Pediatric Nephrology and Dialysis, University Children's Hospital, Sofia, Bulgaria between January 2004 and January 2020. The renal biopsies were examined histologically and with immunohistochemistry at the Pathology Department, Military Medical Academy, Sofia and Medical University – Sofia, Bulgaria. Twenty-eight boys (57.1%) and 21 girls (42.9%) were included in the study. The age at diagnosis ranged from 8 months to 212 months (17 years and 8 months) with a mean of 94 months (7 years and 10 months). Generalized edema was the most common presentation – 55.1%, followed by microhaematuria – 53.1% of cases. Histological examination revealed several different forms: Focal segmental glomerulosclerosis (FSGS) in 30.6% (n=15), Mesangial proliferative glomerulonephritis (MesPGN) in 14.3% (n=7), Membranous glomerulonephritis (MGN) in 12.2% (n=6), IgM nephropathy in 12.2% (n=6), Membranoproliferative glomerulonephritis (MPGN) type I in 8.2% (n=4), C3 glomerulopathy 8.2% (n=4), Minimal change disease (MCD) in 4.1% (n=2), IgA glomerulonephritis in 4.1% (n=2), Diffuse mesangial sclerosis (DMS) in 4.1\% (n=2) and C1q nephropathy in 2.0% (n=1). Although SRNS in Bulgarian children might represent a broad spectrum of glomerular diseases it could be attributed in approximately two/third of patients to four of them – FSGS, MesPGN, MGN, and IgM nephropathy.

Intracranial embryonal neoplasm in an alpaca.

An 11-y-old hembra alpaca was admitted because of cerebellar and vestibular signs, dysphagia, and aspiration pneumonia; without clinical improvement following empirical therapy, the patient was euthanized. On autopsy, a neoplasm was found incorporating the right vestibulocochlear nerve at the level of the acoustic meatus. Histologically, the mass was composed of a multiphasic primitive cell population associated with a dense fibrous stroma and enveloping a remnant ganglion and nerve bundles. Patterns included dense ribbons and cords of embryonal neuroepithelial cells admixed with loosely defined interlacing spindle cells. The embryonal cells had angular cell profiles with variable amounts of lightly basophilic cytoplasm, ovoid-to-irregular nuclei, and an open chromatin pattern with a typically inapparent nucleolus. Necrosis was not evident, and there was 1 mitotic figure per 2.37 mm2. The entire mass was infiltrated by small numbers of lymphocytes and plasma cells. Immunohistochemistry (IHC) revealed strong and diffuse cytoplasmic immunolabeling for vimentin, microtubule-associated protein-2, protein gene product 9.5, and synaptophysin; ~50% immunolabeling for cytokeratin AE1/3; sporadic OLIG2 and S100 immunolabeling; and absent glial fibrillary acidic protein immunolabeling. Based on the histologic pattern and the IHC results, our diagnosis was a poorly differentiated embryonal tumor with ependymal differentiation associated with the vestibulocochlear nerve.

Variant histology of pediatric nodular lymphocyte-predominant Hodgkin lymphoma with IgD and CD30 expression.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), recently known as nodular lymphocyte-predominant B-cell lymphoma (NLPBL), accounts for 5%-10% of Hodgkin lymphoma (HL). Different morphologic patterns of NLPBL are identified and categorized as typical patterns (type A and B) and variant histologic patterns (types C, D, E, and F). We investigated different morphologic patterns, CD30 and IgD expression in pediatric patients with NLPBL diagnosed at the Children's Cancer Hospital Egypt. Forty-six (53%) of the patients exhibited a typical histologic pattern, whereas the remaining (47%) exhibited variant histologic pattern. Variant histology is associated with unfavorable clinical characteristics, such as advanced stages, B-symptoms, and extranodal involvements, particularly bone marrow and bone infiltration, with p-values of .06, .05, and 0.01%, respectively. Additionally, 39% of patients with variant histology experienced disease progression or relapse, compared to only 15.2% of patients with typical patterns (p=.009). Types C and D are related to decreased event-free survival (EFS), as shown by a p-value of .05. The 5-year EFS for patients with variant histology was 94.4% for the rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (RCHOP) versus 33.3% for the adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). IgD expression in lymphocyte-predominant (LP) cells was detected in 44 (50%) patients, while CD30 expression in LP cells was found in 39 (44%) patients. Variant histology of NLPBL was associated with advanced disease stages and a poor prognosis, while expression of IgD and CD30 in LP cells was not. The poor outcome of variant histology improved with the RCHOP regimen.

Infiltrative solid papillary carcinoma of the breast with axillary lymph node metastasis: a case report

BackgroundSolid papillary carcinoma (SPC) is a rare breast papillary tumor variant. The main histological features of SPC consist of neoplastic cell-rich nodules with thin fibrovascular cores, often accompanied by mucous secretion and neuroendocrine differentiation. Infiltrative solid papillary carcinoma (ISPC) tumor cells have an invasive, map-like growth pattern with serrated irregular growth. Due to its unique clinicopathological features, SPC is classified as two pathological tissue types based on the 2019 WHO classification of breast tumors: SPC in situ and ISPC.Case presentationWe report a case of a 55-year-old female patient who was admitted to the hospital due to a painless left breast mass that had persisted for two years. Mammography suggested a mass in the left upper outer quadrant (BI-RADS 4B), and ultrasound of the breast demonstrated a cystic mass of the left breast (US_BI_RADS 4 C) with multiple enlarged lymph nodes in the left axilla. Postoperative pathology revealed ISPC with one lymph node metastasis in the left breast. Modified radical mastectomy was performed on the left breast. Subsequently, the patient received letrozole endocrine therapy, epirubicin hydrochloride and cyclophosphamide chemotherapy, and radiotherapy of the left chest wall and left upper and lower clavicular regions. After 17 months of follow-up, there was no evidence of recurrence or distant metastasis.ConclusionsSPC is a group of heterogeneous tumors. SPC in situ has a good prognosis. In contrast, ISPC has a unique histological morphology and growth pattern with invasive biological behavior that can lead to lymph node and distant metastases.

Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases

Background: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce. Objectives: The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs. Method: An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well. Results: 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4–7.6, p < 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p < 0.01), non-fibrotic ILD (AOR 5.8, p < 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p < 0.01), but similar risk for pneumothorax. Conclusions: Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses.

The histology and growth rate of Nile crocodile (Crocodylus niloticus) claws.

The histology and growth of reptilian and crocodilian claws (ungues) have been extensively studied; however, Nile crocodile (Crocodylus niloticus) claws have not received adequate attention. Furthermore, age estimations for reptilian claws remain unexplored, despite Nile crocodile claws being used in long-term dietary reconstruction studies, assuming certain age-related patterns. In this study, we investigate the histology and growth patterns of Nile crocodile claws, aiming to infer axes for sampling cornified material for radiocarbon dating and establish age estimations for crocodilian claws. Our findings reveal that Nile crocodile claws exhibit growth patterns similar to other reptilians, presenting as modified scutes/scales with an age profile along the sagittal plane. This profile starts at the basal germ matrix and progressively expands in thickness and age dorsoventrally towards the apex or "tip." Consequently, the oldest corneous material is concentrated at the most dorsal point of the claw's apex. To validate previous dietary reconstruction assumptions, we conducted radiocarbon dating on this region of the claw, which supported the idea that retained corneous material in the claws is typically relatively young (5-10 years old) due to abrasion. Our study contributes insights into the histology and growth dynamics of Nile crocodile claws, shedding light on their use in dietary reconstruction studies and emphasizing the significance of considering age-related assumptions in such investigations.

Solitary fibrous tumor of head and neck region; A clinicopathological study of 67 cases emphasizing the diversity of histological features and utility of various risk stratification models

BackgroundHead and neck SFT (HNSFT) exhibit diverse histological features and can mimic various neoplasms with different treatment and behavior. While risk stratification systems have been developed for this tumor at various anatomic sites, a specific scheme for head and neck tumors is lacking. Our aim was to describe the histologic patterns present in HNSFT cases as well as assess the utility of risk assessment models in this location. MethodsA retrospective review of pathology reports and microscopy glass slides of HNSFT cases diagnosed between January 2010 and August 2022 was performed.STAT6 was additionally performed on selected cases if needed. Follow up was obtained and various risk stratification models were applied. ResultsSixty seven cases of HNSFT were collected (age range from 11 to 87 years; median 42 years; M:F 1.6:1). Most common tumor sites were orbit (n = 21; 31.3 %), sinonasal tract (n = 18; 26.9 %), and oral cavity (n = 13; 19.4 %). Tumor size ranged from 1 to 16 cm (median 4cm). Apart from common histological features, tumor cells also showed focal epithelioid morphology, clear cell change and nuclear atypia in a subset of cases. Stromal findings included myxoid and lipomatous change, pseudoglandular spaces, pseudovascular spaces and multinucleated stromal giant cells. CD34 and STAT6 were expressed in 57/67 (85.1 %) and 56/56 (100 %) cases, respectively. Recurrence was observed in 4/26 (15.4 %) cases, while none (0/22) of the patients experienced distant metastasis (follow up 1–150 months; median 20.5 months). Clinical outcome was partially concordant with risk-categories of different risk stratification models. ConclusionKnowledge about histological diversity of HNSFT is essential for establishing correct diagnosis. Current risk stratification models do not perfectly predict outcome, and larger studies are needed to develop more accurate criteria for aggressive behavior.

Neurorosettes: a novel computational modelling framework to investigate the Homer-Wright rosette formation in neuroblastoma

AbstractCancer deregulates the interactions between cells and their microenvironment, leading to disrupted architectures. Homer-Wright rosettes, observed in neuroblastoma, comprise radial arrangements of neurons surrounding a meshwork of fibres. Currently, scientists believe that the presence of Homer-Wright rosettes reflects aberrant neuronal differentiation. Nonetheless, additional understanding of how these structures develop is required since neither experimental nor computational research has characterised this mechanism properly. In this work, we propose a mechanics-based computational framework to investigate Homer-Wright rosette formation. Our model depicts neurons as a combination of spherical (cell bodies) and cylindrical (neurites) agents, and it includes proliferation, neuronal differentiation, and adhesion/repulsion dynamics between neurons. We implemented our framework as an open-source user-friendly Python package called neurorosettes that provides real-time rendering of simulation results, making it adequate for general researchers to test and visualize hypotheses of Homer-Wright rosette formation. Furthermore, we present three example use-cases to replicate the emergence of this rosette subtype and investigate how mechanical interactions between neurons and neuronal differentiation may regulate its architecture. Due to the spare amount of experimental data on the formation of these histological patterns, our applications serve primarily as preliminary examples of how our tool can be used and extended. Although our preliminary results show the relevance of mechanical interactions and poor neuronal differentiation to Homer-Wright rosette formation, these factors appear to only predict the initial stages of rosette formation. Overall, our tool can improve the theoretical knowledge on this process and drive the design of new experimental studies to validate model results.

Histologic pattern analysis of cutaneous basal cell carcinoma at a tertiary care hospital in South India

Basal cell carcinoma (BCC) is one of the common malignant disease of the skin worldwide. An attempt at a simplified, accurate histologic classification of BCC based on histologic growth patterns is done in this study. This paved way to the concept of risk typing BCC into low and high-risk types. This is a retrospective descriptive study of skin biopsies diagnosed as BCC between 2010 and 2018 in the Department of Pathology in a tertiary care teaching hospital in Karnataka. H&amp;E stained sections were reviewed, histopathologically subtyped and further categorized into high and low risk types. IHC for BerEP4 was done in ten diagnostically challenging cases. The patients were followed up for six months after the study period. 79 cases of BCC were studied with majority of them being classified as high risk BCC (83.54%), with nodular type (51.89%) being the most common histological subtype. BCCs were seen predominantly in patients in the sixth decade with a female preponderance in both high and low risk BCCs. Majority of the patients with genetic predispositions were of young age and included xeroderma pigmentosa and oculocutaneous albinism. IHC for BerEP4 showed strong and diffuse membranous staining in all ten cases. Recurrence was noted in two cases and metastasis following three recurrences was noted in one case. An accurate histologic classification of BCC based on growth pattern is of great significance as it reflects the biological behaviour of the tumour. Risk typing BCC into high and low risk types further guides the management of BCC. High risk categories mandate more aggressive and decisive treatment to prevent recurrences and also helps predict the prognosis for the patient.