Investigation of pre-operative demographic, biochemical, sonographic and cytopathological findings in low-risk thyroid neoplasms.

OBJECTIVE: The present article analyses pre-operative demographic, biochemical, sonographic and histopathological characteristics of low-risk thyroid neoplasms (LRTNs), with a focus on four subgroups, "well-differentiated carcinoma-not otherwise specified" (WDC-NOS), "non-invasive follicular thyroid neoplasm with papillary like nuclear features" (NIFTP), "well-differentiated tumours of uncertain malignant potential" (WDT-UMP) and "follicular tumour of uncertain malignant potential" (FT-UMP). METHODS: The study retrospectively analyzed the histopathology of 2453 malignant thyroids and the final analyses included 99 cases diagnosed with LRTNs. The demographic and clinical features, pre-operative thyroid function, ultrasonography results, cytopathology results, histopathology results and prognostic classifications were assessed. RESULTS: The groups were similar demographic characteristics and the majority of clinical data, including comorbidities, thyroid function tests, thyroid cancer/neck radiotherapy history. NIFTPs represented 69.7% of all LRTNs. All (100%) WDT-UMPs had solitary nodules. Index nodule volume differed among the groups (p = .036), it was the lowest in WDC-NOS [0.68 (0.63-0.72 cc)] and highest in FT-UMP [12.6 (0.5-64 cc)]. Echogenicity findings were similar. Index nodule TIRADS demonstrated a significant difference (p = .021) but index nodule halo sign and BETHESDA scores were similar in all groups. The diameter, localisation and multicentric structure of LRTNs were again similar for all groups. Finally, prognostic scores suggested similar outcomes in all groups. CONCLUSION: The majority of LRTNs were NIFTPs in our population and all WDT-UMPs were solitary lesions. Index nodule volume was the most essential discriminating sonographic finding but further research must be performed before discriminatory potential can be described.

Are clinicopathological features of the isthmic thyroid nodule different from nodules in thyroid lobes? A single center experience

ABSTRACT Objectives: Thyroid nodules located in isthmus were found less prevalent, although papillary thyroid cancer in this location was reported to be more aggressive behaviour in some studies. Our aim was to evaluate hormonal,ultrasonographic, and cytopathologic features of nodules located in isthmus (isthmic nodules). Subjects and methods: Patients who underwent thyroidectomy between 2006-2014 reviewed retrospectively. Hormonal, ultrasonographic, and cytopathologic features compared between patients with isthmic (Group-1) and with lober (non-isthmic, Group-2) nodules. Results: Group-1 and Group-2 consisted of 251 and 2076 patients, respectively. 260 isthmic (5.5%) and 4433 non-isthmic (94.5%) nodules were compared.However,most ultrasonographical features such as presence of microcalcification and halo, diameters, echogenicity, texture, margin, and vascularity were similar between groups, macrocalcification rate was lower in isthmic nodules (18.8%, 25.9%; p = 0.012). Cytologic results were also similar.Although malignancy rate was lower in isthmic nodules (6.2%, 12.5%; p = 0.002), type of thyroid cancer was similar in isthmic and non-isthmic nodules.When malignant isthmic (n = 16,2.8%) and malignant non-isthmic nodules (n = 553, 97.2%) were compared, diameter and type of tumor, lymphovascular and capsular invasions, extrathyroidal extension and multifocality rates were not statistically significant.Malignant isthmic nodules (n = 16, 6.2%) had smaller size [10.1 (7.5-34.5) mm, 19.95 (8.4-74.1) mm; p = 0.002], and higher hypoechogenicity rate (31.3%, 5.7%, p = 0.003) compared to benign isthmic nodules (n = 244, 93.8%). Negative predictive value was higher and positive predictive value was lower in isthmic nodules compared to non-isthmic nodules (p = 0.033, p = 0.047, respectively). Conclusion: Isthmic nodules appear to be indolent because of having lower malignancy rate. FNAB might be required in isthmic nodules even if it has relatively small size.The surgery with limited extent or follow-up might seem to be reliable in the management of patients having isthmic nodules especially with indeterminate cytology.

Are clinicopathological features of the isthmic thyroid nodule different from nodules in thyroid lobes? A single center experience.

OBJECTIVE: Thyroid nodules located in isthmus were found less prevalent, although papillary thyroid cancer in this location was reported to be more aggressive behaviour in some studies. Our aim was to evaluate hormonal, ultrasonographic, and cytopathologic features of nodules located in isthmus (isthmic nodules). METHODS: Patients who underwent thyroidectomy between 2006-2014 reviewed retrospectively. Hormonal, ultrasonographic, and cytopathologic features compared between patients with isthmic (Group-1) and with lober (non-isthmic, Group-2) nodules. RESULTS: Group-1 and Group-2 consisted of 251 and 2076 patients, respectively. 260 isthmic (5.5%) and 4433 non-isthmic (94.5%) nodules were compared. However, most ultrasonographical features such as presence of microcalcification and halo, diameters, echogenicity, texture, margin, and vascularity were similar between groups, macrocalcification rate was lower in isthmic nodules (18.8%, 25.9%; p = 0.012). Cytologic results were also similar. Although malignancy rate was lower in isthmic nodules (6.2%, 12.5%; p = 0.002), type of thyroid cancer was similar in isthmic and non-isthmic nodules. When malignant isthmic (n = 16,2.8%) and malignant non-isthmic nodules (n = 553, 97.2%) were compared, diameter and type of tumor, lymphovascular and capsular invasions, extrathyroidal extension and multifocality rates were not statistically significant. Malignant isthmic nodules (n = 16, 6.2%) had smaller size [10.1 (7.5-34.5) mm, 19.95 (8.4-74.1) mm; p = 0.002], and higher hypoechogenicity rate (31.3%, 5.7%, p = 0.003) compared to benign isthmic nodules (n = 244, 93.8%). Negative predictive value was higher and positive predictive value was lower in isthmic nodules compared to non-isthmic nodules (p = 0.033, p = 0.047, respectively). CONCLUSION: Isthmic nodules appear to be indolent because of having lower malignancy rate. FNAB might be required in isthmic nodules even if it has relatively small size. The surgery with limited extent or follow-up might seem to be reliable in the management of patients having isthmic nodules especially with indeterminate cytology.

Enemy Beyond the Wall: Clinicopathological Features of Intrathyroidal Papillary Thyroid Carcinoma (T1-T3a) That Metastasize to Lymph Nodes Without Extrathyroidal Extension.

The aim of this study was to determine the clinicopathological features of papillary thyroid carcinomas (PTC) without extrathyroidal extension (ETE) and with lymph node metastasis (LNM). PTC > 1 cm increased the risk of LNM by 2.161 times compared to papillary thyroid microcarcinoma. The risk increased by 3.774 times in males and 1.553 times in the presence of multifocality. Presence of vascular invasion (VI) increased the risk of LNM by 3.093 times in patients without capsular invasion (CI). Clinicians should be careful about possible LNM in patients with large primary tumor diameter, multifocal tumors, CI and VI.

Diagnosing atypia of undetermined significance in thyroid fine needle aspiration samples using nuclear scoring.

BACKGROUND: Atypia of undetermined significance (AUS) is an indeterminate category in the Bethesda system for reporting thyroid cytopathology. Cytological features described as atypia are not always observed in every case, and it is difficult to determine how the small population of cells with enlarged nuclei, a few grooves, and rare elongated nuclei should be classified. Therefore, there is inter-intra observer variability considering these cell types, even though the cytological criteria are well defined. Therefore, this study aimed to establish a nuclear scoring system to help in the differential diagnosis of AUS. METHODS: Fine needle aspiration (FNA) samples that showed AUS and had surgical follow-up were included in this study. The aspirate was scored for the presence of intanuclear cytoplasmic inclusions, nuclear grooves, overlapping, enlargement, and elongation individually. The total nuclear score for each case was calculated. Statistical analysis of the association between each nuclear feature and the presence of papillary thyroid cancer (PTC) in the surgical specimens was performed. Cut-off points from the total score of these nuclear features were also calculated. RESULTS: Nuclear grooves and overlapping were more common in malignant cases (p < 0.001 and p = 0.048, respectively). A cut-off point of ≥5.5 for the total score was sensitive and specific for defining malignancy. CONCLUSION: The risk of PTC was higher in nodules with more prominent nuclear overlapping or nuclear groove in their FNA samples. In order to achieve a more confident AUS diagnosis, our scoring system can be helpful for thyroid FNA samples.

Correlation of Prognostic Gleason Grade Grouping and Histopathological Parameters: Can the "New System" Reflect the Pathological Perspective for Prognosis?

BACKGROUND: Gleason score is one of the strongest prognostic predictors of prostate cancer;however, a change was published which is a 5 step grouping system of prostatic adenocarcinomas according to their Gleason scores. The aim of this study is to determine the relationship between histopathological findings and prognosis of tumors subgrouped according to the new Gleason grade grouping system. METHODS: A total of 163 radical prostatectomies subgrouped into 5 prognostic groups were investigated for prognostic features such as pathological stage, extraprostatic extension, surgical margin status, involvement of seminal vesicles, perineural invasion, necrosis, vascular invasion, ganglionic involvement, concomitant high grade prostatic intraepithelial neoplasia (HPIN) in addition to other microscopic features of tumors such as the presence of mucin and foamy cytoplasmic change between groups. RESULTS: The mean age of patients was 65.72 ± 6.67 (min = 46, max = 82). Among 131 patients who completed the study, the mean prostate specific antigen (PSA) value was 11.29 ± 10.88. The statistically significant factors were significantly related to both the original Gleason and the prognostic grade groups.The recurrence rate of grade group 4 patients (57%) was significantly higher than grade group 3 patients (8%) (P = 0.038). But no significant difference was found between grade group 4 and 5 (P = 0.25). CONCLUSION: Grade grouping systems reflect prognostic differences but adapting this new system into routine evaluation of patients may confuse the clinicians; however, pathology reports stating both the traditional Gleason score and the new prognostic group may soften the transition.

Cytopathological features of matrix-producing carcinoma of the breast.

Matrix producing carcinoma (MPC) of the breast is a very rare subtype of metaplastic carcinoma with heterelogous elements, which comprises <0.1% of invasive breast carcinomas. There are very few reports describing the cytological features of MPC. In this article, we aimed to discuss cytological, histopathological and immunohistochemical features of this rare entity in a 59-year-old woman.

Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in three cases of neurofibromatosis type 1 (NF1) with a review of the literature.

It is well known that neurofibromatosis type 1 (NF1) is uncommonly associated with pheochromocytoma development and also, to a larger extent, with gastrointestinal stromal tumors (GISTs). We herein document three cases with the rare condition of NF1 coexisting with GIST and pheochromocytoma, while one of them also has a composite tumor and another has papillary thyroid carcinoma.

'Suspicious for papillary thyroid carcinoma' before and after The Bethesda System for Reporting Thyroid Cytopathology: impact of standardized terminology.

BACKGROUND: The high-risk 'suspicious for papillary thyroid carcinoma' (SPTC) is a clinically relevant diagnosis in the cytological interpretation of thyroid aspirates. While The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided invaluable terminology standardization, a performance comparison for this diagnostic category has not been performed. Therefore, this study evaluates the SPTC diagnosis before and after the introduction of TBSRTC in a large meta-analysis and at a single institution. MATERIALS AND METHODS: The meta-analysis analyzed publications of SPTC or similar diagnoses before and after the introduction of TBSRTC. Similarly our own institutional experience was analyzed for the 8 years surrounding the introduction of TBSRTC. A correlation of the cytopathology and surgical pathology diagnoses was performed. RESULTS: The introduction of TBSRTC coincided with a significant decrease in the fraction of cases called SPTC in the meta-analysis (4.5-3.1%, p < 0.00001) and in the institutional review (1.7-0.9%, p = 0.005). Meanwhile, the malignancy risk for those cases increased significantly in the meta-analysis from 62.5 to 80.5% (p < 0.00001) and trended upwards in the institutional review from 69 to 79% (p = 0.4). The follow-up rate was similar in both time periods in the meta-analysis and the institutional review. CONCLUSIONS: The introduction of TBSRTC coincided with a decrease in the fraction of cases called SPTC and an increase in the malignancy risk associated with that diagnosis.

Primary basal cell carcinoma of the caruncle: case report and review of the literature.

A case of primary basal cell carcinoma of the caruncle is presented and patients presented in the literature reviewed. Clinical features and outcome of a patient with primary basal cell carcinoma of the caruncle is described. Review of 8 other cases identified through literature search with the keywords of "basal cell carcinoma" and "caruncle" is presented.A 67-year-old male patient presented with a 12 months' history of a lesion over the caruncular region. Incisional biopsy of the lesion revealed primary basal cell carcinoma of nodular type. MRI of the orbit identified extension of the lesion into the medial orbit. The tumor was excised, and reconstructive surgery was performed. The patient declined subsequent radiotherapy. No recurrence was detected during the follow up of 33 months. The current patient and 8 other patients with primary basal cell carcinoma of the caruncle were reviewed.The main therapeutic approach for primary basal cell carcinoma of the caruncle is complete excision with tumor-free surgical margins. Adjuvant radiotherapy or chemotherapy may be administered when deemed necessary.

Metastases of renal cell carcinoma to the larynx and thyroid: Two case reports on metastasis developing years after nephrectomy.

Renal cell carcinoma (RCC) has a high metastatic potential due to its hematogen and vascular features. It metastasizes frequently to the lungs, the bones, the liver, the lymph nodes and the brain. Metastasis of RCC to the head and neck region is quite rare. In this case report, two RCC patients with head and neck metastases are presented: one occurring after 5 years and the other occurring 17 years after diagnosis.

Nucleophosmin expression in renal cell carcinoma and oncocytoma.

The objective of this study was to investigate nucleophosmin/B23 (NPM) expression in renal cell carcinomas (RCC) and renal oncocytomas. The expression of NPM was studied by immunohistochemical methods on 59 RCCs, 9 oncocytomas, and 19 tumour-negative renal tissues. The expression was assessed relative to various clinicopathological variables and histological subtypes, to determine its potential role as a prognostic and diagnostic marker. All tumours showed nuclear staining, and a minority also exhibited cytoplasmic immunoreactivity. Two patterns of nuclear staining were observed: nuclear staining with a prominent nucleolus (nucleolar staining) and nuclear staining without a prominent nucleolus. There were significant differences, in both nuclear staining and cytoplasmic NPM expression, between oncocytomas and chromophobe RCCs (p < 0.001) and clear cell RCCs (p < 0.001). Cytoplasmic NPM expression was markedly lower in RCCs than in oncocytomas. A statistically significant correlation was discovered between nucleolar staining and nuclear grade (p < 0.001, r = 0.5). No relationship was found between cytoplasmic expression of NPM and any of the clinicopathological parameters or survival. NPM might be a useful immunohistochemical marker for differential diagnosis between oncocytoma and chromophobe RCC. In addition, increased nucleolar NPM expression in RCCs appears to be associated with tumour progression.

Immunohistochemical determination of ETS-1 oncoprotein expression in urothelial carcinomas of the urinary bladder.

ETS-1 protooncogene is an important transcription factor that plays a role in the regulation of physiological processes, such as cell proliferation and differentiation. ETS-1 is thought to be related to the growth of carcinoma cells by its regulation of the transcription of matrix metalloproteinases and urokinase-type plasminogen activator. In this study, we aimed to investigate the expression pattern of ETS-1 oncoprotein in urothelial carcinomas of the urinary bladder and determine its relationship with histopathologic parameters, including tumor grade and stage. One hundred six specimens of urothelial carcinoma and a total of 14 normal urothelium were analyzed immunohistochemically with anti-ETS-1 monoclonal antibody. The normal urothelium showed positive ETS-1 immunostaining. ETS-1 expression remained high in low-grade and noninvasive tumors, whereas it frequently decreased in high-grade or invasive carcinomas. Interestingly, ETS-1 was highly expressed in the basal cell layer of the noninvasive urothelial carcinomas. ETS-1 expression showed a strong negative correlation with the tumor grade (P<0.001; r, -0.67) and stage (P<0.001; r, -0.75). The nonmuscle-invasive tumors (pTa+pT1) and noninvasive tumors (pTa) had significantly higher ETS-1 expression than the muscle-invasive tumors (pT2; P<0.001) and invasive tumors (pT1+pT2; P<0.001), respectively. Results of our study show that decreased ETS-1 expression is significantly associated with high grade and advanced stage in urothelial carcinomas of the urinary bladder, and that the downregulation of ETS-1 expression may be a marker of the aggressiveness of such malignancies.

Association of mast cells with microvessel density in urothelial carcinomas of the urinary bladder.

This study aims to investigate the relation of mast cell (MC) accumulation with tumor grade and stage in urothelial carcinomas of the urinary bladder and to determine its relationship with angiogenesis. A total of 78 urothelial carcinomas obtained by transurethral resection were investigated immunohistochemically by using c-Kit (CD117) and anti-CD34. The correlation between MC counts and microvessels was evaluated and compared with histopathologic parameters including tumor stage and grade. There were significant correlations between MC counts, grade, and stage (P < .05; r = 0.69 and 0.63, respectively). However, MC counts in adjacent nontumoral bladder mucosa significantly were higher than the MC counts in tumoral zone (P < .001). On the other hand, significant correlation was found between the number of MCs in tumoral zone and the microvessel density (P < .05, r = 0.56). The results of our study suggest that c-Kit positive MCs in tumoral zone may contribute to tumor angiogenesis and play a significant role in tumor growth and invasion. Further studies are needed to support these observations.

Epithelioid schwannoma of soft tissue: unusual morphological variant causing a diagnostic dilemma.

Epithelioid variant of peripheral nerve sheath tumors is a rare but, at the same time, a well-known entity especially in the malignant counterpart. However, peculiar epithelioid morphology in soft tissue schwannomas is unusual and has been defined recently. These tumors may cause diagnostic errors owing to their increased cellularity and epithelioid morphology. Typical histologic features of classic schwannoma such as Antoni A and B areas, Verocay bodies, and hyalinized vessels are either absent or only present in focal areas. Furthermore, strong and diffuse S-100 protein expression is seen in both benign and malignant counterparts of epithelioid schwannoma. The findings that are suggestive of the benign nature of the lesion are long-term clinical history, small size, superficial localization, encapsulation, bland morphology, lack of mitosis and necrosis, and a benign clinical course after complete excision. Pathologists should be aware of the epithelioid variant of schwannoma to avoid false diagnosis of malignancy. We hereby report 3 cases of unusual benign epithelioid schwannoma of the soft tissue with special regard to problems in differential diagnosis.

ETS-1 proto-oncogene as a key newcomer molecule to predict invasiveness in laryngeal carcinoma.

ETS-1 protein is one of the key regulators in tumor invasion and progression. We aimed to evaluate the role of ETS-1 in the invasiveness and progression of laryngeal squamous carcinoma, as well as to determine the correlations between clinicopathological characteristics and expression of this molecule. We assessed the levels of ETS-1 in a total of 96 laryngeal specimens of varying degrees of dysplasia, microinvasive squamous carcinoma (8), and invasive squamous carcinoma (60), using normal mucosal epithelium (10) as a positive control. The relationship between ETS-1 expression and clinicopathological parameters of laryngeal carcinoma was also analyzed. We found a significantly higher ETS-1 expression in invasive laryngeal squamous cell carcinomas than in dysplasia (P<0.001). A correlation between ETS-1 expression scores and grade was detected - T factor, stage, cartilage invasion, lymph node metastasis, as well as depth of invasion in laryngeal tumors. Our study is the first to demonstrate that ETS-1 expression is significantly increased in invasive carcinoma, but it is absent in low-moderate grade laryngeal dysplasia and non-neoplastic laryngeal mucosa. This data suggest that ETS-1 expression may play an important role in tumor invasion, and may function in the initiation of the invasive process in laryngeal squamous cell carcinoma.