Histological Features Research Articles

Solid, endometrial-like and transitional growth patterns of ovarian high-grade serous carcinoma: a clinicopathological analysis of 25 cases

Objective: To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC). Methods: Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared. Results: The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20. Conclusions: Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

Gastrointestinal hamartomatous inverted hyperplastic polyps: a clinicopathological analysis of ten cases

Objective: To investigate the clinicopathological features, diagnosis, genetic alterations, and biological behaviors of hamartomatous inverted hyperplastic polyp (HIHP) in the gastrointestinal tract. Methods: The clinical, sonographic, endoscopic and pathologic data of 10 HIHP cases diagnosed at the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2013 to March 2024 were collected. Their clinicopathological features and histological morphology were analyzed. The cases were further divided into 3 histologic subtypes. Follow-up information was collected to analyze the relationship between histological subtype and prognosis. Results: There were 5 males and 5 females in this cohort. The age of onset was 45-68 years, with a median age of 60.5 years. The polyp-involved sites included 2 cases in gastric fundus, 6 cases in gastric body, 1 case in gastric antrum, and 1 case in duodenum. Digestive endoscopy showed mucosal protrusion lesions in all cases, except 1 case (case 10) of shallow depression on the surface, with the maximum diameter ranging 0.5-2.5 cm. Endoscopic ultrasonography showed multilocular cystic low-density shadows, with septal enhancement (case 4). The preoperative clinical diagnosis was gastric polyp, ectopic pancreas or gastrointestinal stromal tumor. Two cases showed type 1 morphology (i.e., connected with the mucosa, with clear smooth muscle boundaries). One of them (case 10) had a clear opening to form a vase-like morphology, while the other (case 4) had no obvious opening with the surface mucosa. Three cases showed type 2 morphology (i.e., not connected with the mucosa, with clear smooth muscle boundaries). Five cases showed type 3 morphology (i.e., not connected with the mucosa, without clear smooth muscle boundaries or hyperplastic smooth muscle that separated hyperplastic glands showing lobular configuration). Among them, one case of duodenal lesions (case 9) showed gastric type gland hyperplasia and expansion, including gastric fossa, gastric fundic gland and pyloric gland, with various arrangement and combination, accompanied by smooth muscle hyperplasia. In case 10, there was leiomyomatous proliferation in the stroma. The cases 2 and 4 had atypical glandular structures and cell morphology, but immunohistochemistry showed wild-type expression pattern of p53 and a Ki-67 proliferation index of less than 1%, suggesting that it was reactive atypia secondary to inflammation. The results showed that 3 cases had different gene mutations, and no recurrent gene change was identified. All patients survived without disease during the follow-up period of 1-130 months. Conclusions: HIHP is a benign lesion and has no consistently detectable genetic alterations. The histological characteristics of gastrointestinal polyps are complex. Especially, the types 1 and 3 of HIHP have unique gross and microscopic features, which require combination of proper endoscopic sampling and histological examination to correctly classify them.

Thiotepa-Induced Toxicity: A Clinical Mimic of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Featuring Severe Mucositis, Diffuse Dusky Discoloration, and Skin Sloughing.

Thiotepa, an alkylating agent commonly used in chemotherapy, is increasingly recognized to induce cutaneous reactions resembling toxic erythema of chemotherapy (TEC). This condition is characterized by erythema, hyperpigmentation, and mucositis, often affecting intertriginous areas, and can mimic the early stages of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). A 31-year-old woman with a history of systemic lupus erythematosus, antiphospholipid antibody syndrome, seizures, and chronic kidney disease was admitted for the management of central nervous system (CNS) lymphoma. Seven days after receiving thiotepa during an autologous stem cell transplant, she developed severe mucositis, requiring intubation for airway protection, followed by a dusky, gray, full-body rash with sloughing in the groin, axillae, and buttocks. A skin biopsy from the back revealed vacuolar interface changes, eccrine gland necrosis, and occasional necrotic keratinocytes at the dermal-epidermal junction, with no evidence of full-thickness necrosis or significant eosinophilic infiltration. The differential diagnosis included thiotepa-induced toxicity, SJS/TEN, and drug eruption. Based on the patient's clinical presentation and the biopsy findings, thiotepa-induced TEC was favored over SJS/TEN. Thiotepa is a potent lipophilic alkylating agent widely used in chemotherapy for pediatric and adult patients with various solid tumors and hematologic malignancies. Its anticancer mechanism involves DNA alkylation, leading to DNA strand cross-linking that disrupts replication and transcription, ultimately inhibiting cancer cell proliferation and survival. While thiotepa is primarily utilized in high-dose preparative regimens for stem cell transplantation in pediatric patients, its use in the adult population remains comparatively limited.This case emphasizes the importance of differentiating thiotepa-induced TEC from severe cutaneous adverse reactions such as SJS/TEN. While these conditions share clinical and histologic features, the absence of extensive epidermal necrosis, satellite cell necrosis, and systemic involvement, along with recent thiotepa exposure, supported a diagnosis of TEC. This case highlights the diagnostic challenge of distinguishing thiotepa-induced TEC from SJS/TEN in post-transplant patients. Recognizing the characteristic involvement of intertriginous areas and eccrine gland necrosis in TEC is critical for accurate diagnosis and management. Awareness of this potential complication in patients receiving thiotepa is essential to avoid misdiagnosis and inappropriate treatment.

Clinicopathologic Features of PRAME-Positive Common Melanocytic Nevi: A Case-Control Study.

Preferentially Expressed Antigen in Melanoma (PRAME) immunohistochemistry has been found to be relatively sensitive and specific for the diagnosis of melanoma, although the detection of PRAME positivity in some melanocytic nevi is a significant limitation. This study was designed to investigate the features of common melanocytic nevi showing PRAME staining, encountered in routine community practice. We reviewed all pathology reports on common melanocytic nevi seen in routine practice for a 1-month period and found that 7.1% of nevi stained with PRAME were considered positive by the original reporting pathologist. A total of 41 PRAME-positive nevi (representing 4.7% of nevi) and a control group of 43 PRAME-negative nevi collected during the same period were identified. The histologic features were reviewed, and the diagnosis and PRAME staining were recorded in a masked fashion by 3 dermatopathologists. Our results suggest that caution is warranted in the interpretation of PRAME in the assessment of small lentiginous melanocytic nevi with a low level of suspicion for melanoma, because these are not infrequently PRAME positive. We found a statistically significant association between the presence of solar elastosis and lentiginous growth pattern, and PRAME status (P < 0.01). When comparing the original diagnosis with the reviewer's diagnosis, the original diagnosis was severely atypical in 54% of PRAME-positive cases, while only 7% were considered to show severe atypia on review masked to PRAME status (P < 0.001). There was no such discrepancy among PRAME-negative cases (9% vs. 19%, considered severely atypical). This finding provides evidence of a "PRAME bias" in the interpretation of melanocytic lesions with no or mild atypia, whereby such lesions are classified as severely atypical when PRAME is positive, likely with the intention of prompting re-excision.

Nodular fasciitis: a case series unveiling novel and rare gene fusions, including two cases with aggressive clinical behavior.

Nodular fasciitis is a benign myofibroblastic tumor characterized by rapid growth and spontaneous regression. While nodular fasciitis is typically an indolent process, rare cases with benign morphologic features have developed metastases. Conversely, nodular fasciitis with malignant histologic features and benign clinical course have also been reported. In this study, we present seven nodular fasciitis cases with novel USP6 gene fusion partners, in addition to two cases with rare fusions that displayed aggressive clinical behavior. The cohort comprised five females and four males with a median age of 36years (range 13-59). Tumors were located in the forearm (n = 3), thigh (n = 2), and shoulder, abdominal wall, chest wall, and oral cavity (one each), ranging from 1.4 to 24.0cm in size (median, 2.2cm). Except for the clinically aggressive cases, patients presented with painless masses of varying onset from days to months. Of the clinically aggressive cases, one patient presented with a slowly growing subfascial thigh/hip mass over nine years, leading to erosion of the femur and pelvis; the other presented with a painful subfascial thigh mass of several months' duration. Histologically, all cases, including the clinically aggressive ones, showed conventional nodular fasciitis features without nuclear pleomorphism or atypical mitotic figures; one case with aggressive clinical behavior exhibited focal infarction-type necrosis. Break-apart FISH analysis using USP6 flanking probes failed to detect USP6 rearrangement in two cases (false negatives) and was inconclusive in one case. Next-generation RNA sequencing identified USP6 fusions in all cases. The clinically aggressive cases showed fusions with COL1A1 (exon 1) and PPP6R3 (exon 1), while novel fusions were identified in the remaining cases including EIF4A1 (exon 1), FILIP1L (exon 2), NF1 (exon 33), OMD (exon 1), PFN1 (exon 1), RLIM (exon 1), and SETD5 (exon 1). Six patients underwent surgical resection; three were managed conservatively, with two experiencing spontaneous tumor resolution. Of the clinically aggressive cases, one patient had progression of the tumor with erosion of the underlying bone, and the second patient developed local recurrence at 14months and lung metastasis at 19months, ultimately dying of disease at 22months. The remaining patients showed no recurrence or metastasis. Our findings expand the spectrum of USP6 gene fusion partners in nodular fasciitis and, for the first time, report cases with conventional morphology exhibiting aggressive behavior, including death. These observations raise the question of whether a subset of deep lesions with conventional nodular fasciitis histology but unusual clinical features, such as large tumor size, represents malignant nodular fasciitis or alternatively a nodular fasciitis-like myofibroblastic sarcoma.

BRCA1-Associated Protein-1 Inactivated Melanoma Arising in a Pre-existing Nevus With ALK Fusion and Low Tumor Mutational Burden.

Breast cancer1-associated protein 1 (BAP-1)-inactivated melanocytic tumors are a group of familial or sporadic lesions with distinctive histology and molecular features. Inherited germline inactivating mutations in BAP1 have been associated with the development of multiple epithelioid melanocytic neoplasms resembling Spitz nevi and increased susceptibility for developing several malignancies, including uveal melanoma, cutaneous melanoma, renal cell carcinoma, mesothelioma, and other tumors. Cutaneous melanoma with loss of BAP1 expression is rare. We present a unique case of BAP1-inactivated melanoma with anaplastic lymphoma kinase (ALK) fusion arising in a pre-existing BAP1-inactivated nevus in a 47-year-old female patient who presented with a dome-shaped red papule on the superior crus of the right antihelix. Histology revealed intradermal melanocytic proliferation with biphenotypic morphology. There was a proliferation of atypical melanocytes showing epithelioid features in the background of nevus. Mitotic figures were identified in the cytologically atypical component of the lesion. Mart-1/Ki67 dual stain demonstrated a higher proliferation index in the larger epithelioid atypical cells, supporting the diagnosis of melanoma. Nuclear BAP-1 expression was lost in the larger atypical cells and associated nevoid cells. Preferentially expressed antigen in melanoma stain demonstrated focal positive staining in 20%-30% of the melanocytes. Immunostaining for B-Raf proto-oncogene, serine/threonine kinase V600E was diffusely positive and ALK demonstrated patchy immunoreactivity in the melanocytic proliferation. Interphase fluorescence in situ hybridization studies showed gains at chromosome 6p25 (Ras responsive element binding protein 1) in the tumor cells. The comprehensive next-generation sequencing revealed B-Raf proto-oncogene, serine/threonine kinase V600E mutation, TP53 mutation, ALK fusion, BAP1 loss (copy number variation = 0.0, potentially germline), and loss of MAP2K7, Von Hippel-Lindau tumor suppressor, FGFR3, CDKN2A, 19q, and telomerase reverse transcriptase. The tumor was microsatellite stable with a low tumor mutational burden (5.76 mutations/Mb). The tumor was completely excised with negative margins. The patient is doing well at 17 months follow-up with no signs of recurrence.

Recurrent respiratory papillomatosis in adults with lower respiratory tract involvement: a retrospective study of the OrphaLung and GETIF networks

BackgroundRecurrent respiratory papillomatosis (RRP) is a rare respiratory disease primarily caused by chronic human papillomavirus (HPV) infection of serotypes 6 and 11. It manifests in childhood (juvenile-onset recurrent respiratory papillomatosis [JoRRP]) and adulthood (adult-onset recurrent respiratory papillomatosis [AoRRP]), leading to progressive obstruction by papillomas in the upper airway and occasionally in the lower respiratory tract (LRT), including the lungs, with a potential for malignant transformation. This study aimed to delineate the characteristics of JoRRP and AoRRP with LRT involvement in adulthood.MethodsA multicenter French-speaking cohort study was conducted, coupled with a comprehensive literature review of clinical, histological, therapeutic, and prognostic features associated with RRP-LRT.ResultsAmong the 122 with LRT involvement with LRT involvement analyzed, 55 (45%) had JoRRP and 67 (55%) had AoRRP. The mean age at diagnosis was 4 years for JoRRP and 54 years for AoRRP. Ear, nose, and throat involvement was observed in all JoRRP cases and in 34 AoRRP cases (51%). Lung involvement occurred in 47 JoRRP cases (85%) and in ten AoRRP cases (15%). Malignant transformation to squamous cell carcinoma in the trachea (n=6) or lung (n=36) was observed in 42 patients (34%). Factors associated with lung involvement included JoRRP, repeated debulking, and malignant transformation; the only factor associated with malignant transformation was lung involvement. Overall mortality was 16%, with JoRRP, lung involvement, and malignant transformation identified as risk factors for death.ConclusionThis study highlights the prevalence of lung involvement and malignant transformation in RRP with LRT and advocates for targeted screening measures and preventive therapeutic strategies.

HEALS-A and GRADES: Novel Histological and Clinical Scales for Assessing Skin Regeneration in Murine Wound Healing Models

Background: Wounds affect approximately 15 out of every 1000 individuals, representing a significant healthcare challenge. The preclinical evaluation of novel wound treatments is important for advancing therapies that promote effective skin regeneration and improve healing outcomes. Methods: In this study, we integrated existing knowledge from the literature on murine wound healing models, histological features of the skin, and clinical scores described in humans to propose two complementary assessment tools: the HEALS-A histological score (healing, epithelialization, angiogenesis, leukocytes, scar tissue, appendages) and the GRADES clinical score (granulation tissue, redness/edema, appearance of wound, devitalized tissue). Results: These scales combine real-time clinical observation with detailed histological analysis, providing a practical and comprehensive approach to assessing wound healing. Unlike existing wound assessing approaches, HEALS-A does not require specialized software and considers regenerated tissue structures, ensuring a broader and more-detailed evaluation. Conclusions: The assessment of wound closure over time, combined with clinical evaluation and histological analysis of skin, provides a comprehensive approach to determining the true impact of new treatments on skin regeneration and the recovery of its functions in wounds.

Phenotyping the Sheep Tail: Histological Depiction of Caudal Spine Structures in Sheep.

The morphology of sheep tails remains relatively understudied. Given the escalating discourse on routine removal of the caudal spine in sheep, a thorough exploration of the anatomical structures within this region is imperative. To examine the tails in detail, this study undertook histological characterisation of three segments (the cranial, middle, and caudal segments) of the tails of 12 undocked Merino sheep lambs. Six lambs were selected for having short tails (37.1 ± 3.0 cm) while the remaining six were chosen for their long tails (49.4 ± 1.7 cm). Immunohistochemical labelling using neuron-specific enolase antibodies was performed to examine the nerve structures in the tail tip. The general structure of the skin resembles that of other domestic mammals. Interestingly, many sweat and sebaceous glands were found in all three tail segments. These findings support the hypothesis that the tails of sheep play a significant role in thermogenesis and perhaps olfactory communication. The study also revealed nerve fibres extending to the tip of the tail. This observation supports the requirement for pain elimination during tail tip amputation.

Reassessment reveals underestimation of infiltration depth in surgical resection specimens with lymph-node positive T1b esophageal adenocarcinoma

AbstractEndoscopic resection (ER) has proven effective and safe for T1 esophageal adenocarcinoma (EAC). However, uncertainty remains concerning risk-benefit return of esophagectomy for submucosal lesions (T1b). Surgical series in past decades have reported significant risk of lymph node metastasis (LNM) in T1b EAC, but these rates may be overestimated due to limitations in histological assessment of surgical specimens. We aimed to test this hypothesis by reassessing histological risk features in surgical specimens from T1b EAC cases with documented LNM.A retrospective cross-sectional study (1994–2005) was conducted. Patients who underwent direct esophagectomy without prior neoadjuvant therapy for suspected T1b EAC with LNM were included. Additional tissue sections were prepared from archival tumor blocks. A consensus diagnosis on tumor depth, differentiation grade, and lymphovascular invasion (LVI) was established by a panel of experienced pathologists.Specific depth of submucosal invasion (sm1 to sm3) was not specified in 10 of 11 archival case sign-out reports. LVI status was not reported in seven of 11 cases. Following reassessment, one patient was found to have deep tumor invasion into the muscularis propria (T2). The remaining 10 of 11 patients exhibited deep submucosal invasion (sm2–3), with five showing one or more additional risk features (poor differentiation and/or LVI).Our findings highlight the potential for underestimating tumor depth of invasion and other high-risk features in surgical specimens. Despite the limited cohort size, our study confirmed a consistent high-risk histological profile across all cases. Caution is warranted when extrapolating LNM risk data from historic heterogeneous cross-sectional surgical cohorts to the modern ER era.

Non-Pharmacological and Pharmacological Approaches to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): An Update

Recently, based on an international consensus, the term The term “non-alcoholic fatty liver disease” (NAFLD) was replaced by “metabolic dysfunction-associated steatotic liver disease” (MASLD). Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and type 2 diabetes mellitus. Lifestyle interventions aiming at substantial weight loss and pharmacological intervention to achieve desired histological outcomes are cornerstones of management of MASLD. Among pharmacological interventions, originally developed as antidiabetic drugs, incretin mimetics and SGLT2 inhibitors were found to reduce steatosis and fibrosis. Certain incretin agonists effectively improve histological features of MASLD. On the other hand, despite mild weight gain, one PPARã agonist (pioglitazone) was found to improve MASLD with certain benefit on fibrosis. Furthermore, benefits of other drug options, which directly target hepatic lipid metabolism (e.g., lipogenesis inhibitors, FGF21 analogs) have also been highlighted. Some combination therapies were also proved beneficial. Our discussion is based on weight loss, glycemic control, reductions of liver enzymes and histological improvement. We have compared results from clinical trials of different drugs as well as systematic review and meta analysis. Mugda Med Coll J. 2024; 7(2): 119-126

Unveiling the intriguing relationship: oncogenic KRAS, morphological shifts, and mutational complexity in pancreatic mucinous cystic neoplasms.

Pancreatic ductal adenocarcinoma (PDAC) often arises from preexisting cystic lesions such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). This study investigated the molecular heterogeneity and mutational landscape of MCN in relation to PDAC, highlighting the significance of KRAS mutations in tumor progression. Utilizing targeted next-generation sequencing on low-grade MCN and invasive PDAC samples, we identified a substantial overlap in mutational profiles, particularly mutations in KRAS, TP53, and FBXW7. Specifically, 69.2% of MCN exhibited somatic mutations, with KRAS mutations being a predominant oncogenic driver. The characterization of mutant versus wildtype KRAS variant allele frequencies (VAF) indicated higher mutation levels in PDAC compared to MCN, suggesting an evolutionary trajectory toward malignancy. Further histological analysis of 12 additional MCN cases revealed significant intratumor heterogeneity, with variant KRAS mutation distributions correlating with distinct cellular morphologies and dysplastic features. Additionally, we explored the potential of liquid biopsies, demonstrating a concordance rate of 71.4% for KRAS mutation detection in circulating tumor DNA (ctDNA) relative to tissue biopsies across cohorts. Our findings underscore the relevance of evaluating KRAS mutations-herein referred to as VAF per microdissected region-as they relate to histopathological markers of dysplasia, contributing to improved stratification of pancreatic lesions and facilitating personalized treatment strategies. In conclusion, this comprehensive analysis of MCN highlights the importance of KRAS as a crucial biomarker for both malignant progression and therapeutic decision-making in pancreatic pathology. Ultimately, our study suggests that characterizing the mutational landscape and histological features of MCN can enhance early detection and intervention strategies for at-risk patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Sclerosing Odontogenic Carcinoma: A Unique Odontogenic Carcinoma with Metastatic Potential.

The recent World Health Organization (WHO) classification of odontogenic tumours defines Sclerosing Odontogenic Carcinoma (SOC) as a rare primary intraosseous carcinoma (PIOC) of the jaws. With the exception of one case, there have been no cases of SOC with metastatic disease. We report a unique case of SOC with neck node metastases, further expanding the clinical, radiological and histological spectrum of this rare intriguing tumour. A 52-year-old female presented with a destructive radiolucent lesion of right mandible. Incisional biopsy was interpreted as desmoplastic ameloblastoma. The segmental mandibulectomy specimen was histologically consistent with SOC with positive anterior margin. Further resection with neck dissection revealed positive right levels IB and IIA nodes. Immunohistochemistry and Fluroscent In Situ Hybridization (FISH) were performed to confirm the diagnosis. The tumour was positive for CK5, p63, p40 and negative for CK19, CK20, CK7, SOX-10, S100, ER, PR, BRAFV600E, and EWSR1 gene rearrangements. Ki67 was 15%. To avoid confusion with PIOC, a high grade squamous cell carcinoma of the jaws with poor prognosis, SOC may be best defined as a rare infiltrative and locally aggressive odontogenic carcinoma with metastatic potential but with a reasonably favourable outcome. SOC shares similar histologic features with many benign and malignant tumours. An appropriate panel of immunohistochemical markers, in conjunction with special stains and molecular studies can help refine the differential diagnosis. It appears that a Ki67 proliferation index of more than 10%, may pose a risk for nodal metastasis and may assist in planning the clinical management. To achieve lower rates of positive margins and tumour recurrence, a wider resection margin (more than a centimetre) is recommended.

Dermatological insight as the key to diagnosing intestinal Behçet's disease misdiagnosed as Crohn's: a case report.

This report presents the case of a 22-year-old male with recurrent genital ulcers, oral aphthae, and gastrointestinal ulcerations initially diagnosed as Crohn's disease by gastroenterologists. Despite overlapping clinical and histological features between Crohn's disease and intestinal Behçet's disease, a dermatological consultation raised suspicion for Behçet's, leading to a revised diagnosis. This case highlights the helpful role of dermatologists in avoiding misdiagnosis and ensuring appropriate treatments for complex inflammatory conditions.

Ultrastructural studies distinguish skin diversities among Galápagos iguanas

Iguanas exhibit diverse colors and behaviors reflecting evolutionarily adaptation to various habitats; in particular, the Galápagos iguanas represent unique color morphologies with distinct ecological niches. While external coloration in iguanas has ecological implications, comprehensive studies on the histological and ultrastructural aspects of their skin can provide insight into their adaptation to extreme environments, such as high UV exposure. Starting from these considerations the present study investigates the histological, ultrastructural and immunohistochemical features to comprehensively characterize the skin in adults of three species of Galápagos iguanas (A. cristatus, C. subcristatus and C. marthae). Morphological analysis revealed significant differences among the species, with the black-colored skin of A. cristatus showing a melanin-rich but vessel-poor dermis, while C. subcristatus and C. marthae displayed varying distributions of melanosomes and melanocytes. Notably, the absence of iridophores was consistent across all samples due to the absence of birefringent material under the optical microscope. Morphometric evaluations highlighted interspecific differences in the stratum corneum thickness, particularly between black- and non-black-colored (irrespectively if yellowish or pink) skin. The ultrastructural investigation confirmed the absence of iridophores in all analyzed samples. The cytokeratin expression assessed by immunohistochemistry showed stratified epithelium in the epidermis of C. marthae non-black-colored (pink) skin. The presence of a thickened stratum corneum and the stratification of the epidermis in non-pigmented skin could help the pink iguana to cope with the extreme conditions of the Wolf volcano, especially in relation to UV exposure. These skin characteristics may reduce the penetration power of UV rays into the superficial loose dermis, thereby attenuating potential UV-related damage such as DNA breaks and ROS generation. These findings offer insights into the adaptive strategies of these iguanas.

Efficiency of medical leech on experimentally induced incisional wound healing in rats.

This study was conducted in response to the increasing interest in understanding the effects of both modern and traditional complementary medicine on incisional wound healing. Herein, it was aimed to investigate the wound healing effects of medicinal leech therapy and leech saliva in an experimentally created incisional skin wound model. Fifteen rats underwent full-thickness incisions on their dorsal regions and were randomly assigned to five equal groups, as the Leech Saliva (LS) group, where wounds were treated topically with leech saliva once daily; Leech Therapy-1 (LT-1) group, where leech therapy was administered once at the beginning of the experiment; Leech Therapy-2 (LT-2) group, where leech therapy was applied twice, on days 0 and 3; Positive Control (PC) group, where wounds were treated daily with Phyto cream containing Triticum vulgare; and Negative Control (NC) group, where no treatment was given. Wound healing was assessed daily, and the experiment continued until complete healing was observed. At the conclusion, the wound size, appearance, and histological features were analyzed to compare healing progress across the groups. Medicinal leech therapy was observed to have a positive wound healing effect in the rat model.

Updated Review of Cellular Dermatofibroma: Benign or Not?

Cellular dermatofibromas (CDFs) are uncommon benign fibrous histiocytomas with histologic patterns resembling malignancies. Despite their benign nature, CDFs can recur and metastasize. Physicians are uncertain about the management of CDF, given its resemblance to dermatofibrosarcoma protuberans. This review aims to review CDF's clinical and histologic features, differentiate it from similar presenting malignancies, and discuss treatments and outcomes for better clinical management. In April 2024, a PubMed and Google Scholar search was completed using "cellular dermatofibroma" through the University of California Davis Medical School's library databases. The search included meta-analyses, randomized controlled trials, observational studies, reviews, and case studies published within the past 70 years. References from retrieved articles were utilized as additional resources. Clinical signs of CDF include firm, skin-colored to hyperpigmented lesions usually larger than 2 cm, typically on extremities. Currently, there are no definitive indicators for CDF recurrence or metastasis. Diagnosis requires microscopic and histopathologic examination, with surgical excision as the preferred treatment. Recurrence is not uncommon, while metastasis is rare. CDFs often develop in young/middle-aged adults with a tendency to recur and in rare cases can metastasize. Future studies could explore lesion characteristics that are associated with potential for recurrence and metastasis.

Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review.

In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.

Evaluation of the effects of smoking on the clinical and histological characteristics and levels of growth factors in autologous fibrin membranes.

Considering the increase in regenerative dental treatments, autologous fibrin membranes (ARMs) have been widely used in tissue engineering, favoring the regeneration of hard and soft tissues, accelerating angiogenesis and promoting cell differentiation and migration. This study proposed evaluate the differences in clinical characteristics and levels of the growth factors BMP-2, IGF, PDGF and VEGF between smokers and nonsmokers were evaluated according to the guidelines of the US Preventive Service Task Force (USPSTF). Fourteen smokers and 14 nonsmokers were selected. After processing, the samples were allowed to rest in tubes for 5min for the organization of the matrix and completion of the fibrin clot. Only the yellow portion and the buffy coat were removed and stored. Four clots were obtained from each donor and used to quantify the release of the growth factors BMP2, PDGF, IGF and VEGF. In addition, histological analyses were performed, and clinical characteristics were evaluated. The data were tabulated and subjected to statistical analysis with a significance level of 5%. In both groups, the membranes remained intact throughout the analysis period, indicating similar structural behavior. Histological evaluation of the membranes obtained from the participants revealed the presence of more homogeneous fibrin membranes in the nonsmoker group and many leukocytes bordering the entire fibrin clot. In the smoker group, heterogeneous fibrin clots, sometimes malformed, and fewer leukocytes in the region of the buffy coat and bordering the entire fibrin were observed. Smokers had significantly lower levels of VEGF, PDGF and BMP-2 (pg/ml in 1µg total protein) than smokers did (p < 0.05), and there was no significant difference in IGF levels (p > 0.05) between the groups. There was also no statistically significant difference in membrane size between smokers and nonsmokers (mm, p > 0.05). Smoking may interfere with the formation of the fibrin mesh and consequently affects the quality and regenerative capacity in in smoking patients.

Clinicopathological and molecular characterization of astrocytoma

IntroductionAstrocytoma is a rare tumour of the central nervous system that often manifests with non-specific clinical symptoms and lacks distinct histological features. There is a pressing need for further understanding of the clinicopathological and molecular characteristics of astrocytoma. Identifying mutant genes can aid in reliable and early diagnosis, as well as provide insights for the development of targeted therapies.MethodsThis study aims to investigate the clinicopathologic and molecular characteristics of astroblastoma. A total of four patients diagnosed with astroblastoma were included in the analysis. Clinical features, histological findings, and immunohistochemistry results were reviewed and analyzed. Genetic alterations were identified using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), followed by patient follow-up.ResultsThe study included four female patients, ranging in age from 8 to 44 years. One patient had a tumour in the right parietal lobe, while the other three had tumours in the spinal cord. Histology is usually characterized by pseudorosettes of astroblasts and hyalinization of blood vessels. These tumors showed a growth pattern similar to traditional intracranial astroblastoma, and the histological manifestations of the four patients were all high-grade, showing features of high-density areas of tumor cells or necrosis. Immunohistochemical staining revealed that all four patients expressed OLIG2, EMA, and vimentin, while three patients also expressed GFAP and S-100. The Ki-67 positivity index was approximately 15% in three cases and 10% in one case. Fluorescence in situ hybridization (FISH) using break-apart probes showed EWRS1 breaks in three patients and MN1 breaks in one. Further DNA or RNA-targeted biallelic sequencing identified an EWSR1(Exon1-7)-BEND2(Exon2-14) fusion in case 1, and an EWSR1(Exon1-7)-BEND2(Intergenic) fusion in case 2. In case 3, an EWSR1(Exon1-7)-NUDT10(Intergenic) fusion was present, and in case 4, an MN1(Exon1)-BEND2(Exon2) fusion was identified. The EWSR1-NUDT10 gene fusion is a new fusion type in astroblastoma. The patients were followed up for 76.5, 17.6, 33.7, and 61.3 months, respectively. Three cases experienced tumour recurrences at the spinal cord site, with multiple recurrences in case 4.DiscussionOur study unveiled the distinctive clinicopathological and molecular mutational characteristics of astrocytoma, while also identifying rare mutated genes. Additionally, the detection of MN1 or EWSR1 gene fusion through FISH or next-generation sequencing can provide valuable insights into the molecular mechanisms and aid in the differential diagnosis of astrocytoma.