Langerhans cell histiocytosis of the suprasellar region: diagnosis based on thyroid cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up.

Knowledge of cytology results affects the performance of colposcopy: a crossover study.

OBJECTIVE: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). METHOD: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. RESULTS: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. CONCLUSIONS: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

Unusual phosphaturic mesenchymal tumor mimicking osteoid osteoma.

Phosphaturic mesenchymal tumor is a rare tumor characterized by paraneoplastic osteomalacia. The diagnosis is often delayed because of nonspecific symptoms and difficulty to localize the tumor. In this study we report a case of PMT of the left femur detected by Ga-68-DOTATATE PET-CT with radiological features mimicking osteoid osteoma. We report a 31-year-old female patient who presented to our hospital for evaluation due to progressive bone pain and muscle weakness. Her laboratory data showed hypophosphatemia and increased fibroblast growth factor 23 (FGF-23) together with reduced bone mineral density on bone densitometry. The diagnosis of PMT was suspected and the tumor was identified on Ga-68-DOTATATE PET-CT as a focal uptake in a lucent lesion of the left femoral head with a central sclerotic dot mimicking a nidus as seen in osteoid osteoma. The lesion was treated with percutaneous radiofrequency ablation. Laboratory tests and bone densitometry rapidly improved post-treatment. The present case emphasizes the difficulty to diagnose PMT due to its nonspecific biochemical and clinical presentation and the relevance of functional imaging for locating these tumors despite different radiological presentation.

What morphological MRI features enable differentiation of low-grade from high-grade soft tissue sarcoma?

Objective: To assess the diagnostic performance of morphological MRI features separately and in combination for distinguishing low- from high-grade soft tissue sarcoma (STS). Methods and materials: We retrospectively analysed pre-treatment MRI examinations with T1, T2 with and without fat suppression (FS) and contrast-enhanced T1 obtained in 64 patients with STS categorized histologically as low (n = 21) versus high grade (n = 43). Two musculoskeletal radiologists blinded to histology evaluated MRI features. Diagnostic performance was calculated for each reader and for MRI features showing significant association with histology (p < 0.05). Logistic regression analysis was performed to develop a diagnostic model to identify high-grade STS. Results: Among all evaluated MRI features, only six features had adequate interobserver reproducibility (kappa>0.5). Multivariate logistic regression analysis revealed a significant association with tumour grade for lesion heterogeneity on FS images, intratumoural enhancement≥51% of tumour volume and peritumoural enhancement for both readers (p < 0.05). For both readers, the presence of each of the three features yielded odds ratios for high grade versus low grade from 4.4 to 9.1 (p < 0.05). The sum of the positive features for each reader independent of reader expertise yielded areas under the curve (AUCs) > 0.8. The presence of ≥2 positive features indicated a high risk for high-grade sarcoma, whereas ≤1 positive feature indicated a low-to-moderate risk. Conclusion: A diagnostic MRI score based on tumour heterogeneity, intratumoural and peritumoural enhancement enables identification of lesions that are likely to be high-grade as opposed to low-grade STS. Advances in knowledge: Tumour heterogeneity in Fat Suppression sequence, intratumoural and peritumoural enhancement is identified as signs of high-grade sarcoma.

ABCD criteria to improve visual inspection with acetic acid (VIA) triage in HPV-positive women: a prospective study of diagnostic accuracy.

OBJECTIVES: A simple system for visual inspection with acetic acid assessment, named ABCD criteria, has been developed to increase accuracy for triaging of high-risk human papillomavirus (HPV)-positive women. This study aimed to determine the accuracy of ABCD criteria for the detection of histologically confirmed cervical intraepithelial neoplasia grade two or worse (CIN2+) in HPV-positive women living in a low-resource setting. DESIGN: Prospective study of diagnostic accuracy. SETTING: Cervical cancer screening programme based on a 3T-Approach (test, triage and treat) in the Health District of Dschang, West Cameroon. PARTICIPANTS: Asymptomatic non-pregnant women aged 30-49 years were eligible to participate. Exclusion criteria included history of CIN treatment, anogenital cancer or hysterectomy. A total of 1980 women were recruited (median age, 40 years; IQR 35-45 years), of whom 361 (18.4%) were HPV-positive and 340 (94.2%) completed the trial. INTERVENTIONS: HPV-positive women underwent a pelvic examination for visual assessment of the cervix according to ABCD criteria. The criteria comprised A for acetowhiteness, B for bleeding, C for colouring and D for diameter. The ABCD criteria results were codified as positive or negative and compared with histological analysis findings (reference standards). PRIMARY OUTCOME MEASURE: Diagnostic performance of ABCD criteria for CIN2+, defined as sensitivity, specificity, negative and positive predictive values. RESULTS: ABCD criteria had a sensitivity of 77.5% (95% CI 61.3% to 88.2%), specificity of 42.0% (95% CI 36.5% to 47.7%), positive predictive value of 15.1% (95% CI 10.8% to 20.8%), and negative predictive value of 93.3% (95% CI 87.6% to 96.5%) for detection of CIN2 +lesions. Most (86.7%) of the ABCD-positive women were treated on the same day. CONCLUSIONS: ABCD criteria can be used in the context of a single-visit approach and may be the preferred triage method for management of HPV-positive women in a low-income context. TRIAL REGISTRATION NUMBER: NCT03757299.

A cross-sectional study exploring triage of human papillomavirus (HPV)-positive women by visual assessment, manual and computer-interpreted cytology, and HPV-16/18-45 genotyping in Cameroon.

BACKGROUND: High-risk human papillomavirus (HPV)-positive women require triage to identify those at higher risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We aimed to compare visual assessment of the cervix, manual cytology and automated cytology as triage tests to screen HPV-positive women, and to assess over-treatment rates after visual assessment and over-referral rates to colposcopy after cytology. METHODS: The present cross-sectional study is nested in a large prospective screening trial in Cameroon. Evaluations of the tests have been conducted individually and in combination with HPV-16/HPV-18/45 genotyping. For the evaluation of over-treatment and colposcopic over-referral, we simulated two screening scenarios: (1) one-visit scenario (test-triage-and-treatment); and (2) two-visit scenario (test-triage-and-colposcopy). RESULTS: 1582 women with a median age of 40 years (IQR 35-45) performed self-sampling for HPV testing, of which 294 (18.6%) were HPV-positive, and 12.2% had CIN2+. Sensitivities for CIN2+ detection were 77.1% for visual assessment, 80.0% for manual cytology, and 84.8% for automated cytology. Sensitivity of combined tests was higher compared with single tests. The highest sensitivity was obtained by the combination of genotyping and automated cytology (91.2%). In the one-visit scenario, the over-treatment rate was 83.9% in referred women, with a ratio of 6.2 treated women per CIN2+. In the two-visit scenario, the lowest over-referral rate would have been under manual cytology (45.0%), with a ratio of 1.8 referred women per CIN2+. Single and combined triage strategies by automated cytology gave rise to over-referral rates of 69.2% and 76.7%, respectively, and a ratio of 3.2 and 4.3 referred women per CIN2+, respectively. DISCUSSION: Triage of HPV-positive women using a combination of genotyping and automated cytology for CIN2+ detection may provide public benefits in low- and middle-income countries.

Concordance of tumour characteristics and survival clustering among pairs of first-degree relatives with breast cancer.

BACKGROUND: Family history is a known risk factor for breast cancer, but its prognostic value and the prognostic value of tumour characteristics in relation to family history has not been clearly established. In addition, studies of intra-familial tumour characteristics and prognosis in population-based settings are very rare. Two previous studies have suggested that breast cancer prognosis clusters within families. However, both studies lack information on HER2 expression status, which is a strong prognostic factor and could contribute to the observed results. METHODS: We conducted a population-based study on 145 mother-daughter and sister-sister affected pairs using data extracted from the Geneva Cancer Registry. Histopathological characteristics were determined in archived tumour blocks by immunochemistry techniques. Breast cancer survival among family members was studied according to patient and tumour characteristics. RESULTS: No significant intra-familial agreement of pathological characteristic features was observed. We found that relatives of breast cancer patients experienced a much higher risk of breast cancer death compared to the general population. However, we did not find significant concordance in good and poor breast cancer-specific survival between pairs. The small number of family pairs and deaths from breast cancer may partly explain our results. CONCLUSIONS: Large-scale studies with accurate data on strong prognosticators are still needed to confirm the possibility of familial inheritance of breast cancer prognosis.  .

IDH1 immunohistochemistry reactivity and mosaic IDH1 or IDH2 somatic mutations in pediatric sporadic enchondroma and enchondromatosis.

Mosaic somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes have been identified in most enchondromas by targeted mutation analysis. Next-generation sequencing (NGS), that may detect even low-level mosaic mutation rates, has not previously been applied to enchondromas. Immunohistochemistry using the H09 clone is routinely used as a surrogate for the common R132H IDH1 mutation in gliomas. We compared immunohistochemistry and NGS results in a series of 13 enchondromas from 8 pediatric patients. NGS identified a heterozygous IDH mutation in all enchondromas, showing identical mutation status in patients with multiple tumors assessed, thereby confirming somatic mosaicism. A majority of the tumors harbored an IDH1 mutation (p.R132H in 3 tumors; p.R132C in 4 tumors from 2 patients; p.R132L and p.R132G in one tumor each). A p.R172S IDH2 mutation was identified in 4 enchondromas, but not in the ependymoma from one patient with Ollier disease, who further displayed a heterozygous STK11 missense mutation. IDH mutation rates varied between 14% (indicative of mutations in 28% of the cells and of intratumoral mosaicism) and 45% (tumor content was close to 100%). Cytoplasmic H09 reactivity was observed as expected in tumors with an IDH1 p.R132H mutation; cross-reactivity was seen with the p.R132L variant. This first NGS study of pediatric enchondromas confirms that IDH mutations may occur in a mosaic fashion. STK11 gene mutations may provide insights in the development of multiple cartilaginous tumors in enchondromatosis, this tumor suppressor gene having been shown in animal models to regulate both chondrocyte maturation and growth plate organization during development.

Vulvar intraepithelial neoplasia grade 3 associated with Behçet's disease.

BACKGROUND: Little information is available regarding the association between vulvar intraepithelial neoplasia grade 3 (VIN3) and Behçet's disease (BD). We report here concomitant VIN3 and genital ulcers in a patient with BD. CASE: A 44-year-old Caucasian woman with a history of BD, which had been evolving for 6 years, presented with ulcerated and papillomatous lesions on the vulva. Biopsies revealed a multifocal VIN3 positive for high-risk human papillomavirus (HPV) 33. Multiple biopsies were performed to exclude invasive cancer and VIN3 was treated with laser vaporization. CONCLUSION: We report clinical and anatomopathological features of a rare case of multifocal, high-risk, HPV-related VIN3. We also discuss the possible pathogenesis in the context of BD, featuring chronic ulceration and intrinsic or treatment-induced immunosuppression.

Giant Cell Tumor of Bone With Pseudosarcomatous Changes Leading to Premature Denosumab Therapy Interruption: A Case Report With Review of the Literature.

Denosumab has shown promising results in the management of giant cell tumor of bone, a primary bone tumor with locally aggressive behaviour. We report a case of premature denosumab interruption due to radiological and clinical tumor expansion of a giant cell tumor of the distal ulna. Although denosumab is known to induce tumor regression, with progressive ossification and loss of the characteristic morphology of giant cell tumor of bone, the ulnar tumor specimen showed a moderately to highly cellular proliferation of short spindle-shaped cells, and no osteoclast-like giant cells. There were no abnormal mitotic figures. We considered the surgical specimen as a giant cell tumor of bone with partial regression after prematurely interrupted denosumab treatment. This case illustrates the diagnostic issues of an initially unfavourable evolution raising concern for malignancy, and the difficulties in histological assessment of a partially treated giant cell tumor of bone, that may mimic osteosarcoma.

Immune-mediated experimental arthritis in IL-33 deficient mice.

Previous work suggested implication of the interleukin (IL)-1 family cytokine IL-33, signaling through its receptor ST2, in the pathogenesis of human and mouse arthritis. In this study, we directly investigated the role of endogenous IL-33 in antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) using IL-33 KO mice. AIA was induced by injection of methylated bovine serum albumin (mBSA) into knee joints of previously immunized mice. CIA was induced by immunization with bovine type II collagen. Disease severity was evaluated by clinical and histological scoring and cellular immune responses were assessed in cultured draining lymph node cells. Our results indicate that the development of AIA or CIA, as assessed by clinical or histological evaluation, is not impaired in IL-33 deficient mice. We did not observe any consistent modifications in humoral or cellular immune responses in IL-33 KO mice, although IL-33 deficiency enhanced antigen-specific IFN-γ production, proliferation or IgG2a titers in some experiments, suggesting that endogenous IL-33 may contribute to shaping the adaptive immune response. In conclusion, our data suggest that IL-33 plays a modifying rather than a pivotal role in disease development in two models of immune-mediated arthritis.

[Fibroblastic and myofibroblastic tumors of the head and neck]. / Tumeurs fibroblastiques et myofibroblastiques de la tête et du cou.

Fibroblastic and myofibroblastic tumors of the head and neck are numerous and may develop either in adults or in childhood. They can be benign and nonrecurring, benign but locally recurring, of low-grade of malignancy or fully malignant. The diagnosis and treatment of these lesions can be difficult. This review focuses on several (myo)fibroblastic lesions of the head and neck, including nodular fasciitis and related neoplasms, hemangiopericytoma-like tumor (glomangiopericytoma) of sinonasal passages, nasopharyngeal angiofibroma, desmoid fibromatosis, Gardner-associated fibroma, extrapleural solitary fibrous tumor, inflammatory myofibroblastic tumor, low-grade myofibroblastic sarcoma, and adult-type fibrosarcoma.

Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.

BACKGROUND & AIMS: Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice. METHODS: In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies. RESULTS: Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P < .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P < .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P < .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P < .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P < .01], respectively). CONCLUSIONS: IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.

[Primary synovialosarcoma: a case of unusual location]. / Le synovialosarcome primitif: a propos d'une localisation inhabituelle.

AIM: Report a new case of primary Synovialosarcoma. CASE: We report a case of a 16 year old girl, who presented with a tumefaction on the right clavicle evolving for 3 months. Various explorations carried out, in particular thoracic scanner and imagery by magnetic resonance, showed a multilocular cystic formation of the seat and the clavicle reaching the mediastinum. A pathological examination of the part (piece) highlighted a biphasic synovialosarcoma of grade III. This diagnosis was validated by the immunohistochemistry study and the detection of transcribed specific fusion of the synovialosarcoma, SYT-SSX1. CONCLUSION: The unusual locations of the primitive SS must be known because the diversity of their microscopic aspects may cause confusion in the diagnosis. The immunohistochemistry, and more recently the cytogenetic studies, helps to solve these problems of differential diagnosis.

[Digestive polyposis. Retrospective study of 20 cases]. / Les polyposes digestives. Etude rétrospective d'une série de 20 patients.

BACKGROUND: Three main polyposis syndromes are transmitted as an autosomal dominant disorder: familial adenomatous polyposis (FAP), juvenile polyposis syndrome (JPS) and Peutz-Jeghers syndrome. AIM: Evaluate this management of digestive polyposis. METHODS: Our study included 20 patients which were collected in th departements of pathology surgery and garstroenterology of MT Maarmouri's Hospital, Nabeul city. RESULTS: We reported 15 cases of adenomatous polyposis with 2 family groups. We identified a family group of JPS with 3 members and 2 cases of Peutz-Jeghers syndrome. We found 11 cases of colonic adenocarcinoma out of the 15 patients affected by adenomatous polyposes. FAP is a generalized disorder involving the entire colorectum segment with numerous extra-colonic manifestations. The risk to develop colonic cancer is 100%. JPS is characterised by the development of numerous gastrointestinal juvenile polyps and occurs usually before 20 years old, the progression to cancer is rarely observed. CONCLUSION: Peutz-Jeghers syndrome consists in hamartomatous polyps associated to a characteristic mucosal pigmentation. The patients are usually young adults and have an increased incidence of cancer in extradigestive sites.

[Inflammatory fibroid polyp of the ileum presenting as intussusception: a case report in an adolescent]. / Polype fibro-inflammatoire de l'intestin grele revele par une invagination intestinale aigue: a propos d'un cas chez une adolescente.

Inflammatory fibroid polyp is an uncommon and benign submucosal lesion of the gastrointestinal tract. The maximal incidence is in the fifth and sixth decades. The main histological characteristics are diffuse inflammatory infiltrate with eosinophils and highly vascularized fibrocystic stroma. We report a case of 15-year-old patient who underwent emergency surgery because of acute intestinal obstruction as a result of an intussusception. The macroscopical study after segmental ileal resection showed a nodular lesion 3x2x2 cm, arising from the submucosa with an ulcerated surface. The pathologic diagnosis was ileal inflammatory fibroid polyp. Immunohistochemically, the cells reacted with vimentin and CD34. It has no malignant potential although extensive infiltration may occur. The etiology is unknown. We discuss the clinical, the pathological aspects and the possible etiological factors of the inflammatory fibroid polyp.

[Hepatic mesenchymal hamartoma in adulthood: a case report with literature review]. / Hamartome mesenchymateux du foie chez l'adulte: a propos d'un cas avec revue de la littérature.

Mesenchymal hamartoma is a rare and benign tumor.. Representing 5 to 8 % of children's hepatic tumors, it is rarely described in adults. Authors report a new case of hepatic mesenchymal hamartoma in a 21-year-old woman, diagnosed after a sudden onser of clinical and biological cholestasis. Abdominal US and CTscan exminations showed a medial liver tumor with cystic formations suggestive of a hydatid cyst. The diagnosis of hepatic mesenchymal hamartoma was based onn hitology of the resected liver specimen. Radiological findings can suggest the diagnosis but only histology can confirm it. Treatment is surgical involving in most of the cases; a wide hepatic resection because of the size of the tumor. Progosis is excellent when complete exeresis is possible.