Nondiagnostic Test Result Rates Following Thyroid Extra-Fine-Needle Aspiration.

OBJECTIVES: The first Bethesda classification category of thyroid fine-needle aspiration biopsy (FNAB) is nondiagnostic (ND), which indicates that the specimen's cellularity is inadequate for evaluation. This work investigated the effect of needle diameter size on ND rates by comparing diagnostic outcomes of FNAB samples collected with 23-, 25-, and 27-gauge needles. METHODS: This was a retrospective analysis of samples collected from patients undergoing FNAB between 2018 and 2021. It was conducted in an otolaryngology department in a university teaching hospital. RESULTS: Of the 699 aspirations, 144, 335, and 220 were performed using 23-, 25-, and 27-gauge needles, respectively. ND rates increased significantly when using 27-gauge compared with 23- to 25-gauge needles (P = .002), and a significantly lower ND rate was found for the 25-gauge needle compared with the 27-gauge needle (P = .001). Furthermore, increased nodule size was associated with reduced ND rate (odds ratio, 0.801; 95% confidence interval, 0.691-0.929). CONCLUSIONS: The 25-gauge needles are superior to 27-gauge needles in reducing ND rates of thyroid nodule FNAB specimens. Future prospective studies should be performed to confirm these findings.

Coexisting Epithelioid Trophoblastic Tumor and Placental Site Trophoblastic Tumor During Asymptomatic Relapse: A Case Report and Literature Review.

Gestational trophoblastic neoplasms are a group of trophoblastic tumors that include choriocarcinoma (CC), epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms include combinations of CCs with ETTs and/or PSTTs; combinations of ETTs and PSTTs have also been described. This report describes the case of a 49-yr-old female with mixed ETT and PSTT discovered due to menstrual delay and a positive beta-human chorionic gonadotropin in serum 11 yr after normal pregnancy; it is an asymptomatic recurrence of the neoplasm after 2 yr. Moreover, only the ETT recurred without evidence of PSTT by biopsy and without any increase in human chorionic gonadotropin levels, even though human chorionic gonadotropin was positive in the first onset of the disease. We also reviewed published English literature, which revealed that there are only 36 cases of mixed trophoblastic tumors to date, of which pure mixed ETT and PSTT were reported only in four cases including our case. The most common combination is CC admixed with an ETT (52%), followed by CC with PSTT in 30.5%. CC admixed with an ETT and/or PSTT account for 83% of the cases, of which pure mixed ETT and PSTT were reported only in 4 cases (11%). The rarity of this condition entails reporting of all cases to facilitate future research and clinical management.

Effect of needle gauge on thyroid FNA diagnostic rate.

PURPOSE: Thyroid Bethesda classification system provides 6 diagnostic categories, the first being a sample deemed non-diagnostic or insufficient and requiring a subsequent second biopsy. Our objective was to evaluate differences in non-diagnostic fine needle aspiration (FNA) of thyroid nodules conducted with a 23-gauge(G) needle vs. those conducted with a 25 G needle. METHODS: Data from 298 aspiration procedures using either 23 G or 25 G needles were collected, including cytological findings, ultrasound characteristics and patient demographics. The samples were classified as diagnostic or non-diagnostic according to final cytology. RESULTS: There was no statistically significant difference between the 25 G and 23 G needles in terms of non-diagnostic rates (35.7%, 31.9%; p = 0.494). Nodules defined as cystic had higher non-diagnostic rates (p < 0.05). Older patients as well as cystic nodules were associated with a higher non-diagnostic rate (OR = 1.018, p = 0.047, OR = 13.533, p = 0.0001, respectively), while nodule size was associated with lower non-diagnostic rates (OR = 0.747, p = 0.017). CONCLUSIONS: The use of 25 G needle did not produce a lower non-diagnostic rate when compared to 23 G needle. Larger nodules might increase diagnostic rates, while older patients and cystic nodules are prone to inadequate samples. Patients and caregivers should be aware that FNA of small or cystic nodules as well as nodules in older patients may result in a higher non-diagnostic rate. Further research comparing other needles gauges should be conducted.

Hemorrhagic Malignant Pleural Effusion: Diagnosis, Survival Rate, and Response to Talc Pleurodesis.

Hemorrhagic malignant pleural effusion (HMPE) is diagnosed in 47-50% of all malignant pleural effusions (MPE). The aim of this study is to evaluate clinical, radiological, and morphological manifestations of HMPE and results of talc pleurodesis treatment. This is a retrospective review of the medical charts of 135 MPE patients which consists of HMPE group (42 patients) and simple MPE group (63 patients) (median age 67.9 years; 43 males, 62 females). In HMPE vs. simple MPE patients, pronounced dyspnea (100% vs. 88.9%, P = 0.024), chest pain (59.5% vs. 60.3%, P = 1), general deterioration (78.6% vs. 74.6%, P = 0.411) combined with large pleural effusion (81% vs. 50.8%, P = 0.001), and thickening of parietal pleura (73.8% vs. 68.3%, P = 0.349), all were more specific for HMPE. Cytological examination of HMPE showed more malignant pleural fluid cells (81% vs. 63.5%, P = 0.043). Histological examination revealed poorly differentiated types of tumors in 69.05% of HMPE (bronchogenic 33.33%, intestinal 16.67%, breast 14.3%) vs. 7.94% of simple MPE. In 19 HMPE vs. 0 simple MPE patients, thoracoscopy showed bleeding nodules (94.7%) on thickened parietal pleura (84.2%). Pleurodesis with talc by slurry (59%) and poudrage (41%) was less effective in HMPE than in simple MPE patients after 1 month (failed response; 33.3% vs. 21.6, P = 0.019), 3 months (42.9% vs. 25.7%, P = 0.017), and 6 months (42.9% vs. 21.7%, P = 0.035). Survival in HMPE was significantly lower (3.06 months vs. 5.37 months, P = 0.0005). HMPE has more severe clinical, laboratory, radiological, and endoscopic manifestations due to a more poorly differentiated malignant process. Talc pleurodesis was less effective in HMPE, and survival was poor.

Not All Bethesda 1 Thyroid Nodules Were Created Equal: Different B1 Subgroups.

OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology is a uniform method used worldwide to report thyroid fine-needle aspiration (FNA) outcomes. This study focuses on the Nondiagnostic/Unsatisfactory category, designated as Bethesda1 (B1). The documented risk of malignancy for B1 nodules can vary significantly, implying this category is not homogenous and might be composed of different subtypes. Our hypothesis was that B1 subgroups (blood only, insufficient thyrocytes, cyst content) will vary in their malignancy rate. METHODS: The study design was observational and retrospective. The study population included 154 patients in the Galilee Medical Center who underwent FNA examination of the thyroid gland from 2013-2018 and had a B1 result. We looked at the final diagnosis of malignant or benign for patients who underwent surgery and calculated the malignancy rate for each subgroup. RESULTS: Malignancy rates were higher in the Blood subgroup than in the other subgroups, and higher in the Thyrocytes subgroup than in the Cyst subgroup (P < .05). All malignancies were papillary thyroid carcinomas. There was no significant difference in the malignancy rate when we further divided the B1 samples into 2 groups based on the presence of epithelial cells. Many repeat FNA tests resulted in a different B1 subgroup. CONCLUSION: The different malignancy rates suggest that individual management approaches should be considered for each B1 subgroup.

Differences in cytopathologist thyroid nodule malignancy rate.

OBJECTIVES: The accuracy of a cytological diagnosis obtained by fine needle aspiration is influenced by several factors including the technique used and the experience of both the aspirator as well as the cytologist. In this project we planned to evaluate the interobserver differences of thyroid nodule cytopathology in our medical centre. METHODS: The study was conducted using retrospective pathology reports from a single academic centre from August 2013 to September 2017. We compared the sensitivity, specificity, negative and positive predictive values, malignancy rates, and accuracy of two cytopathologists who evaluated thyroid nodules. RESULTS: We included 287 fine needle aspirations of thyroid nodules in the study. Approximately one fifth (18.5%) of patients had surgery and the rate of malignancy was 40%. There was a similar frequency of use of all thyroid Bethesda system (TBS) categories with the exception of TBS 3 (8.0% and 21.2%, P = .01). As a consequence, the malignancy rate was different in TBS 3 category (40% vs 17%, P = .545). CONCLUSIONS: There are interobserver differences in the evaluation of thyroid nodules. Clinicians should be aware of such differences because they affect the malignancy rate in each TBS category.

Flow cytometry aneuploidy and cell cycle indexing as a possible tool for differentiating between CD10+ diffuse large B-cell lymphoma and follicular lymphoma.

BACKGROUND: Differential diagnosis between diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) becomes a challenge when adequate biopsy is unavailable. The present study aimed to investigate the applicability of DNA cell cycle analysis by flow cytometry (FC) for differentiating between CD10+ DLBCL and FL. METHODS: Data were collected from 57 specimens where CD5- /CD10+ /light chain restricted B cells were detected. DNA staining was performed using the Coulter DNA Prep Kit. Cell cycle fractions were evaluated by automatic analysis using the ModFit LT software. RESULTS: Histopathological analysis confirmed the diagnosis of CD10+ FL in 30 specimens (52.6%), CD10+ DLBCL in 24 specimens (42.1%), and CD10+ Burkitt lymphoma in 3 specimens (5.3%). A significantly higher rate of DNA aneuploidy was detected among CD10+ DLBCL than FL specimens (50 vs. 13.3% respectively, p = .003). Likewise, DNA index was significantly higher in CD10+ DLBCL relative to FL (1.26 ± 0.35 vs. 1.04 ± 0.16 respectively, p = .004). Notably, the proportion of cells in the S-phase and proliferative fraction was significantly higher in CD10+ DLBCL than in CD10+ FL (S-phase: 15.97 ± 13.94 vs. 4.43 ± 4.41 mean ± SD, respectively, p < .0001; proliferative fraction: 18.87 ± 15.17 vs. 5.78 ± 7.04 mean ± SD, respectively, p = .0001). Using a receiver operating characteristic analysis, optimal cutoffs for S-phase ≥7% and proliferative fraction ≥9% were determined. These values could be used to differentiate between CD10+ DLBCL and CD10+ FL. CONCLUSION: Including DNA cell cycle analysis in the FC lymphoma assessment panel may be of diagnostic value in differentiating between CD10+ DLBCL and FL when adequate biopsy is unavailable.

Review of a single institution's fine needle aspiration results for thyroid nodules: Initial observations and lessons for the future.

OBJECTIVE: Our objective was to evaluate the disease spectrum of thyroid cytopathology and correlation of the Bethesda reporting system with final histopathology in our medical centre. METHODS: This retrospective study was conducted from histopathology reports from Galilee Medical Center between August 2013 and September 2017. RESULTS: A total of 287 thyroid fine needle aspirations were included in the study. The majority (55.1%) of these were benign (B2). Surgery was performed on 53 cases and the total malignancy rate was 39.6%. Our study had a favourable accuracy rate of 70%. A B4 Bethesda category had a higher malignancy rate (50%) than previously reported. CONCLUSION: We found a higher malignancy rate (50%) based on the Bethesda B4 category of the fine needle aspirations in our series, yet it is based on a small sample. The differences in malignancy rates between centres have an important impact on clinical decisions.

Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.

BACKGROUND: Thoracic and abdominal aortic aneurysms and dissection often develop in hypertensive elderly patients. At higher risk are smokers and those who have a family history of aortic aneurysms. In most affected families, the aortic aneurysms and dissection is inherited in an autosomal dominant manner with decreased penetrance and variable expressivity. Mutations at two chromosomal loci, TAA1 at 11q23 and the TAA2 at 5q13-14, and eight genes, MYLK, MYH11, TGFBR2, TGFBR1, ACTA2, SMAD3, TGFB2, and MAT2A, have been identified as being responsible for the disease in 23% of affected families. RESULTS: Herein, we inform on the clinical, genetic and pathological characteristics of nine living and deceased members of a large consanguineous Arab family with thoracic aortic aneurysm and dissection who carry a missense mutation c.4471G > T (Ala1491Ser), in exon 27 of MYLK gene. We show a reduced kinase activity of the Ala1491Ser protein compared to wildtype protein. This mutation is expressed as aortic aneurysm and dissection in one of two distinct phenotypes. A severe fatal and early onset symptom in homozygous or mild late onset in heterozygous genotypes. CONCLUSIONS: We found that MYLK gene Ala1491Ser mutation affect the kinase activity and clinically, it presents with vascular aneurysms and dissection. We describe a distinct genotype phenotype correlation where; heterozygous patients have mild late onset and incomplete penetrance disease compared with the early onset severe and generally fatal outcome in homozygous patients.

Small intestinal amyloidosis: a rare cause of diverticular disease.

Systemic amyloidosis frequently involves the small intestine. However, its association with diverticular disease has been seldom reported to date. To draw attention to this rare but potentially harmful association, we herein present an additional case of small bowel diverticular disease associated with amyloidosis.

Intrapulmonary solitary fibrous tumors: clinicopathologic and immunohistochemical study of 24 cases.

Solitary fibrous tumor (SFT) is a ubiquitous neoplasm that arises most commonly from the pleura. SFT arising within lung parenchyma (intrapulmonary SFT) has been rarely reported and is therefore not well recognized. We present a clinicopathologic and immunohistochemical study of 24 cases of primary intrapulmonary SFT. Patients' ages ranged from 44 to 83 years (mean, 58 y). None of the patients had evidence or history of a similar tumor elsewhere. Tumor size ranged from 2.3 to 22 cm (mean, 8.5 cm). On the basis of the degree of cytologic atypia, cellularity, mitotic activity, and areas of necrosis, the lesions were divided into low-grade, intermediate-grade, and high-grade histology. Twenty-one tumors showed the conventional features of SFT of low-grade histology (<5 mitoses per 10 high-power fields), with alternating bands of rope-like collagen flanked by a bland-appearing spindle cell proliferation. Hemangiopericytic, angiofibromatous, and a neural-like plexiform growth pattern were also observed. Five of 21 cases showed an "adenofibromatous" appearance imparted by entrapped normal airspaces at the advancing edges of the lesion. One intermediate-grade tumor showed overall increased cellularity with plump, pleomorphic nuclei, 5 to 10 mitoses per 10 high-power fields, and focal areas of classic SFT. Two cases showed high-grade features at initial presentation, with areas resembling a pleomorphic high-grade sarcoma admixed with foci of conventional, low-grade SFT. Immunohistochemical staining analyses performed in 13 cases showed positivity of the tumor cells for CD34, bcl-2, and CD99 in the majority of cases tested. Clinical follow-up was available in 18 patients, with long-term follow-up (>5 y) in 6. Fourteen (14/18) patients were alive and well without evidence of disease 1 month to 14 years after initial diagnosis. Three patients died of their tumors after 4, 5, and 7 years; in 2 of them the initial tumor was of low-grade histology, but the recurrence/metastases showed a high-grade histology; the third fatal case showed a tumor with high-grade histology at initial diagnosis. One patient with intermediate-grade histology also had chest wall metastases at 5 years but was subsequently lost to follow-up. The results of our study indicate that although tumors with overtly malignant histologic features can be expected to behave as high-grade sarcomas, tumors with bland-appearing morphologic features at presentation may also follow an aggressive behavior. Adequate excision with close clinical follow-up, thus, appears to be the most prudent course of action for the management of primary intrapulmonary fibrous tumors.

A founder mutation in Vps37A causes autosomal recessive complex hereditary spastic paraparesis.

BACKGROUND: Members of two seemingly unrelated kindreds of Arab Moslem origin presented with pronounced early onset spastic paraparesis of upper and lower limbs, mild intellectual disability, kyphosis, pectus carinatum and hypertrichosis. METHODS: The authors performed neurological and developmental examinations on the affected individuals. The authors conducted whole genome linkage and haplotype analyses, followed by sequencing of candidate genes; RNA and protein expression studies; and finally proof of principle investigations on knockdown morpholino oligonucleotide injected zebrafish. RESULTS: The authors characterise a novel form of autosomal recessive complex hereditary spastic paraparesis (CHSP). MRI studies of brain and spinal cord were normal. Within a single significantly linked locus the authors ultimately identified a homozygous missense mutation c.1146A>T (p.K382N) in the vacuolar protein sorting 37A (Vps37A) gene, fully penetrant and segregating with the disease in both families. Mobility was significantly reduced in Vps37A knockdown morpholino oligonucleotide injected zebrafish, supporting the causal relationship between mutations in this gene and the phenotype described in the patients of this study. CONCLUSIONS: The authors provide evidence for the involvement of Vps37A, a member of the endosomal sorting complex required for transport (ESCRT) system, in upper motor neuron disease. The ESCRT system has been shown to play a central role in intracellular trafficking, in the maturation of multivesicular bodies and the sorting of ubiquitinated membrane proteins into internal luminal vesicles. Further investigation of mechanisms by which dysfunction of this gene causes CHSP will contribute to the understanding of intracellular trafficking of vesicles by the ESCRT machinery and its relevance to CHSP.

Gene expression differences between colon and rectum tumors.

PURPOSE: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level. EXPERIMENTAL DESIGN: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons. RESULTS: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum. CONCLUSIONS: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer.

Unusual case of pancreatic inflammatory myofibroblastic tumor associated with spontaneous splenic rupture.

BACKGROUND: Spontaneous splenic rupture considered a relatively rare but life threatening. The three commonest causes of spontaneous splenic rupture are malignant hematological diseases, viral infections and local inflammatory and neoplastic disorders. We describe a unique and unusual case of inflammatory myofibroblastic tumor of the tail of pancreas presented with massively enlarged spleen and spontaneous splenic rupture. CASE PRESENTATION: A 19 years old male patient with no significant past medical history presented to emergency room with abdominal pain and fatigue. Massively enlarged spleen was detected. Hypotension and rapid reduction of hemoglobin level necessitated urgent laparatomy. About 1.75 liters of blood were found in abdominal cavity. A large tumor arising from the tail of pancreas and local rupture of an enlarged spleen adjacent to the tumor were detected. Distal pancreatectomy and splenectomy were performed. To our knowledge, we report the first case of massively enlarged spleen that was complicated with spontaneous splenic rupture as a result of splenic congestion due to mechanical obstruction caused by an inflammatory myofibroblastic tumor of the tail of pancreas. A review of the literature is also presented. CONCLUSION: Inflammatory myofibroblastic tumor of the tail of pancreas should be included in the differential diagnosis of the etiological causes of massively enlarged spleen and spontaneous splenic rupture.

Mammary-digital-nail (MDN) syndrome: a novel phenotype maps to human chromosome 22q12.3-13.1.

Mammary-digital-nail syndrome is a novel phenotypic association consisting of anonychia onychodystrophy with hypoplasia or absence of distal phalanges in males and females, accompanied by juvenile hypertrophy of the breast in affected females. This newly described genetic trait presents an autosomal dominant inheritance pattern, with either reduced penetrance or germ-line mosaicism. Analysis of the pedigree, linkage studies followed by a genome-wide screen and by haplotype analysis defined the locus for the phenotype within a 12 cM (4.3 Mb) interval on chromosome 22q12.3-13.1. This chromosomal region has not been implicated before in genetic disorders of the mammary tissue or limbs. These data suggest a possibly novel signaling pathway affecting the organogenesis of limbs and mammary glands in humans.