The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas.

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Mucins, trefoil factors and pancreatic duodenal homeobox 1 expression in spasmolytic polypeptide expressing metaplasia and intestinal metaplasia adjacent to gastric carcinomas.

INTRODUCTION: Gastric cancers are the second cause of cancer related deaths all around the world but gastric carcinogenesis remains a mystery. Intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) are the two types of preneoplastic metaplasias. In this study, we aimed to investigate expression of Pancreatic duodenal homeobox 1 (PDX1), mucins (MUCs), trefoil factors (TFFs) in SPEM and IM surrounding gastric carcinomas. MATERIAL AND METHODS: Tissue samples of tumor adjacent gastric mucosa including IM (n = 61) and SPEM (n = 36) from 70 gastrectomy specimens were used for immunohistochemical analysis of PDX1, mucins (MUC5AC, MUC6) and trefoil factors (TFF2, TFF3). RESULTS: Nuclear expression of PDX1 was present in both SPEM (32/36) and IM (60/61) and there was no significant difference in expression of PDX1 between the two types of metaplasias. While TFF3 and MUC5AC were abundant in IM, SPEM showed 100% expression of TFF2 and MUC6 and also lower positivity with TFF3 and MUC5AC. PDX1 positivity was related to expression of MUC5AC (60/61, p < 0.001) and TFF3 (60/61, p < 0.001) in IM and also associated with expression of MUC5AC (14/32, p < 0.05), MUC6 (32/32, p < 0.001), TFF2 (32/32, p < 0.001) and TFF3 (9/32, p < 0.05) in SPEM. Coexpression of TFF3 and TFF2 was present in 10 of 36 (27.7%) samples of SPEM and also 29 of 61 (47.5%) samples of IM exhibited dual expression of trefoil peptides. CONCLUSIONS: PDX1 may affect the development of SPEM and IM. Expression patterns of TFFs and MUCs may indicate that IM evolves from SPEM.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

TERT Expression in Pituitary Adenomas.

OBJECTIVE: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. MATERIAL AND METHOD: The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. RESULTS: TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). CONCLUSION: This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.

Comparison of clinicopathological features in incidental and nonincidental papillary thyroid carcinomas in 308 patients.

Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

Histological perspective on the effects of tumor-associated macrophages in the tumor microenvironment surrounding papillary thyroid carcinoma.

Tumor-associated macrophages (TAMs) are one of the most noticeable elements of the tumor microenvironment. The present study investigated the relationships between the density of CD163 immunolabeled M2-like TAMs with other histological properties of the tumor microenvironment and clinipathological features in 90 patients with papillary thyroid carcinomas (PTC). The percentage of TAMs was higher in tumors with significant lymphocytic tumor response (p = 0.020), in tumors with a significant degree of stromal tumor response (p = 0.014), those with infiltrative tumor borders (p = 0.029), in conventional variant papillary carcinoma (p = 0.032), and in patients with autoantibodies for thyroid peroxidase (p = 0.014). The tumors associated with lymphocytic thyroiditis had lower numbers of TAMs (p = 0.027). In conclusion, for the first time, the present study attempts to establish a full assessment of interactions of CD163 expressing M2-like TAMs with the triad of primary tumor- tumor microenvironment- tumor behavior and above all, with markers of autoimmunity. Thus, these alternatively polarized macrophages may act in tumor progression and dissemination according to their various products, which may be ordered by tumor cells or neighboring immune cells. The molecular studies may reveal their roles in various tumors and may improve the therapy strategies targeting TAMs in various malignant tumors, including PTCs.

Histopathological Evidence of Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Prophylactic lymph node dissection is still controversial due to the potentially surgery-related morbidity in management of papillary thyroid carcinomas. So, some histopathological predictors for lymph node metastasis in thyroidectomy specimens may reveal importance. The objective of this study was to define histomorphological indicators of lymph node metastasis in the patients who had been performed thyroidectomy without lymph node dissection. Clinicopathological features of patients archived in Department of Pathology at Trakya University Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as papillary carcinoma and had been performed total thyroidectomy/lobectomy with central/cervical lymph node dissection were included in the study. Clinical features (age, gender, preoperative/postoperative clinical, and laboratory findings) and histopathological features (histological variant, tumor size, focality, extrathyroidal extension, tumor border, lateral tubular growth, intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic lymph nodes, extranodal extension, size of the metastatic foci) were evaluated. Male gender, conventional variant, tumor size greater than 10 mm, multifocality, extrathyroidal extension, lateral tubular growth, intraglandular dissemination, lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis were predictive, and older age (≥45 years) and follicular variant PTC were protective for lymph node metastasis. In order to optimize the management of papillary thyroid carcinomas, pathologists should search for the clues of lymph node metastasis particularly intraglandular dissemination, lateral tubular growth, tumor border and lymphocytic/stromal tumor response, multifocality, concomitant lymphocytic thyroiditis besides the actual prognostic criteria especially in younger aged male patients.

Histopathological Features of Gastrointestinal Stromal Tumors and the Contribution of DOG1 Expression to the Diagnosis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) have KIT or platelet-derived growth factor receptor α (PDGFRα) mutations affecting receptor tyrosine kinase activity and do not benefit from classic treatment regimens. AIMS: The aim of this study was to review the algorithm that may be followed for the diagnosis and differential diagnosis in GISTs by investigating the histomorphological parameters and expression characteristics of classical immunohistochemical antibodies used in routine tests in addition to DOG1 expression. STUDY DESIGN: Diagnostic accuracy study. METHODS: We reevaluated the histological and immunohistochemical parameters of 37 GISTs. The standard immunohistochemical diagnosis and differential diagnosis panel antibodies (CD117, PDGFRα, CD34, vimentin, desmin, SMA, S-100, and Ki67) were studied on the tumor sections. We also used the popular marker DOG1 antibody with accepted sensitivity for GISTs in recent years and the PDGFRα immune marker for which the benefit in routine practice is discussed. RESULTS: Classification according to progressive disease risk groups of the 37 cases revealed that 54% were in the high risk, 19% in the moderate risk, 16% in the low risk, 8% in the very low risk and 8% in the no risk group. Cytological atypia, necrosis, mucosal invasion and the Ki67 index were found to be related to the progressive disease risk groups of the tumors (p<0.05). Positive immunoreaction was observed with CD117 and PDGFRα in all GISTs in the study (100%). Positivity with the DOG1 antibody was found in 33 (89%) cases. CD34 was positive in 62% (23) of the cases. CONCLUSION: The CD117 antibody still plays a key role in GIST diagnosis. However, the use of DOG1 and PDGFRα antibodies combined with CD117 as sensitive markers can be beneficial.

Congenital Pulmonary Airway Malformation Type 2: A Case Report with Review of the Literature.

A congenital pulmonary airway malformation is a rare disorder of the pulmonary airway and a hamartomatous mass of disorganized lung tissues with various degrees of cystic change. A 20-year-old pregnant woman who did not have previous clinical follow-up during her pregnancy visited the gynecology department for her first check on the 19th week of gestation. The sonogram, showed severe hydrops fetalis. Laboratory findings were consistent with non-immune hydrops fetalis. Medical abortion was performed and the fetus was sent to our department for a complete fetal autopsy. Macroscopically, whole parts of the fetus had striking oedema. Massive pleural and peritoneal effusions were seen on dissection. The left lung filled the whole thoracic cavity. The heart was displaced to the right and the right lung was compressed. Microscopically, the left lung mass showed dilated bronchiole-like structures (1-20 mm) that were lined with ciliated columnar cells without any intervening mucinous cells. The subepithelial stroma contained thin, interrupted smooth muscle fibers and elastic connective tissue without cartilage plates. Our case is a very good example of non-immune hydrops fetalis associated with congenital pulmonary airway malformation type 2. Prenatal clinical and ultrasonographic follow-ups during pregnancy are very important for early diagnosis of congenital malformations.

The relationship among PDX1, CDX2, and mucin profiles in gastric carcinomas; correlations with clinicopathologic parameters.

PURPOSE: Several studies performed on pancreatic-duodenal homeobox 1 (PDX1) have demonstrated a loss of expression and negative tumor modulator effect in gastric carcinoma. Relations between PDX1 and gastric metaplasia, differentiated type of gastric carcinoma, and the early stage of the disease have been exhibited in previous reports. The aim of this study was to examine expressions of PDX1, caudal type homeobox 2 (CDX2) and mucin (MUC) profiles to address the role of PDX1 in gastric carcinogenesis and its relationship with CDX2. METHODS: Seventy gastrectomy specimens were analyzed immunohistochemically for PDX1, CDX2, MUC2, MUC5AC, and MUC6 expressions. The sum of cytoplasmic and nuclear PDX1 immunostaining and PDX1 positivity were assessed. All of the antibodies were examined for a correlation with tumor type, clinicopathologic parameters, and metaplasias. The relation of Ki-67 proliferation index with the expression profiles was also investigated. RESULTS: Neither PDX1 (66/70) nor CDX2 (37/70) and the mucin profiles (MUC2:11/70, MUC5AC:48/70, MUC6:41/70) showed a significant difference between differentiated and undifferentiated types of gastric carcinoma and clinicopathologic parameters. The PDX1 expression frequency was 94.3%, with an average PDX1 score of 8.8 ± 4.2. PDX1 and CDX2 expression showed a significant difference (P = 0.026 and P = 0.002, respectively) among the phenotypic classification of gastric carcinomas. All of the gastric and intestinal mixed-phenotype gastric carcinomas (GI-type) showed both PDX1 and CDX2 immunopositivity. Except for the relation of PDX1 score with MUC6 expression, no significant difference was detected between PDX1 and CDX2, MUC2, and MUC5AC expressions. A relationship between CDX2 and MUC2 and also between MUC5AC and MUC6 was found statistically. The Ki-67 proliferation index revealed a significant positive correlation with PDX1, CDX2, and MUC2 positivity. CONCLUSIONS: PDX1 expression revealed a higher positivity in gastric carcinomas than the previous studies and showed no relation with tumor type, clinicopathologic parameters, CDX2 expression, or mucin profiles. However, a significant relation of PDX1 and CDX2 expressions among phenotypic classification of gastric carcinomas reveals an idea about similar functions for PDX1 and CDX2 in the evolution of gastric carcinoma.

Massive upper gastrointestinal bleeding from pure metastatic choriocarcinoma in patient with mixed germ cell tumor with subclinical intestinal metastasis.

Although testicular germ cell tumors have become curable neoplasms, a better understanding of the clinicopathologic features is needed for the rare manifestations associated with treatment failure. We report a rare case of metastatic pure choriocarcinoma involving the small intestine arising from a testicular mixed germ cell tumor. In a patient who developed massive upper gastrointestinal hemorrhage during treatment, the intestinal metastases and focus of bleeding could only be determined by laparotomy. We propose an approach for the determination of subclinical intestinal metastases of testicular germ cell tumor; the case is discussed in light of similar reports in literature.

Lung, bone, skeletal muscles and cutaneous metastases from adenoid cystic carcinoma of the parotid gland: a case report and review of the literature.

Adenoid cystic carcinoma is the second most common malignancy of the major and minor salivary glands after mucoepidemoid carcinoma. The risk of distant metastases is approximately 20-50%. Although bone, the central nervous system and the other organs may become involved, the lungs are favored sites for metastases. Skeletal muscle and cutaneous metastases from adenoid cystic carcinoma of the parotid gland are extremely rare. In this case, a 40-year-old man with lung and bone metastases followed by skeletal muscle and cutaneous metastases from adenoid cystic carcinoma of the right parotid gland is presented.

Ovarian hemangioma presenting with hyperandrogenism and endometrial cancer: a case report.

BACKGROUND: Hemangiomas are very rare tumors of the ovary. Here, we report a case of a mixed capillary and cavernous ovarian hemangioma and endometrial carcinoma presenting with postmenopausal bleeding, male pattern receding frontal hairline, and high serum androgen and estradiol levels. CASE: A 70-year-old White female underwent laparotomy for endometrial carcinoma. Intraoperative frozen-section examination of the uterus revealed a 3.5 x 3 cm, grade 1 endometrioid adenocarcinoma of the endometrium with more than 50% myometrial invasion. The left ovary contained a 1.5 x 1 x 1 cm, well-circumscribed hemorrhagic nodule on the cut surface. Final histopathological examination of the small nodule demonstrated multiple, enlarged, blood-filled vascular channels lined by a single layer of flattened regular endothelial cells with no atypical features. Vascular spaces within the tumor were of different sizes, ranging from small to large, and were separated by connective tissue. The surrounding ovarian stroma was hyperplastic and contained clusters of luteinized stromal cells. Microscopy of the right ovary showed minimal stromal proliferation and no luteinization of the ovarian stroma. CONCLUSION: This is the first case of an ovarian hemangioma synchronous with a well-differentiated endometrial carcinoma. Absence of estrogen and progesterone receptors in the endothelial cells of the hemangioma suggests that ovarian hemangiomas may occur independent of stimulation by estrogen and progesterone.

Evaluation of tumor angiogenesis with contrast-enhanced dynamic magnetic resonance mammography.

The goal of this research was to correlate dynamic magnetic resonance (MR) mammographic contrast enhancement and microvessel densities in breast masses. Forty-six female patients with breast masses detected by mammography and/or ultrasonography were included in the study. MR contrast enhancements of the lesions were investigated dynamically using axial three-dimensional fast low-angle shot sequences. After excisional biopsy or mastectomy, immunohistochemical staining with factor VIII-RA was performed, followed by microvessel density measurements. Contrast enhancement patterns in dynamic MR mammography were compared with microvessel density measurements using Student's t-test, Pearson's moment correlation coefficients, and one-way analysis of variance (ANOVA). Malignant lesions exhibited three different enhancement patterns: 1) a peak enhancement within 120 seconds (early phase), followed by a decrease in the delayed phase (25 cases); 2) an increase in the early phase, followed by a plateau in the delayed phase (9 cases); and 3) an increase throughout the examination without any peak (5 cases). In benign lesions, signal intensity did not exhibited a peak in five cases, whereas in two cases enhancement was increased in the early phase and made a plateau in the delayed phase. A significant correlation was found between microvessel density and the percentage of maximal signal increase following paramagnetic contrast administration (r=0.322, p<0.05). Dynamic enhancement patterns and rates of maximal signal increase predict microvessel density in breast malignancies and may possibly be used as prognostic indicators.