Çiğdem Vural

Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-2: Prognostic biological markers in invasive prolactinomas

In this study, the predictive roles of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and 2 in invasive and noninvasive prolactinomas were examined. Prognostic biomarkers to distinguish between invasive and noninvasive pituitary adenomas are required for the effective treatment of pituitary adenoma patients. We analyzed 57 prolactinoma patients classified as having invasive and noninvasive adenomas for MMP-9, TIMP-1 and TIMP-2 expression using immunohistochemical methods. Significantly higher MMP-9 expression was detected in invasive prolactinomas (p=0.004). There was also a significant relationship between TIMP-2 expression and invasive behavior (p=0.004) and TIMP-2 expression and recurrence (p=0.005). Because MMP-9 expression is significantly increased in invasive prolactinomas, MMP-9 has potential as a marker for invasion. TIMP-2 may be a marker for both invasion and recurrence. These findings require further examination in large scale prospective studies.

Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature.

Esophageal cancer is a poor-prognosis malignancy that ranks eighth among all cancer types, and its prevalence shows differences among geographical regions. Although the most important risk factors for esophageal carcinoma are alcohol and smoking, viral infections, particularly HPV infection, are also considered among etiological agents. Our study aims to detect the presence of HPV in esophageal cancers in our patient population and to investigate its correlation with clinico-pathological parameters. We investigated the presence of HPV-DNA by real-time polymerase chain reaction in a total of 52 patients with esophageal cancer. Subtype analysis was performed in positive cases and was correlated with selected clinico-pathological parameters. Five (9.6%) of 52 tumor samples, 3 squamous cell carcinomas (3/33 cases) and 2 adenocarcinomas (2/19 cases), were HPV-DNA-positive. Subtype analysis could be performed in four HPV-DNA-positive cases, of which three were HPV type-39 and 1 was type-16. The Marmara region, where the present study was carried out, is a region with low-moderate risk for esophageal cancer, and the prevalence of HPV-DNA in these tumors is similar to the prevalence of HPV-DNA reported in the literature for regions with similar risk. In conclusion, we detected HPV DNA in a subset of esophageal and gastroesophageal junction tumors. HPV infection may have a role in esophageal carcinogenesis and high-risk HPV subtypes can particularly be considered among risk factors since the prevalence of high risk HPV infection has also been found to be increased in regions with a high risk for esophageal cancer compared to low-moderate risk regions.

Subacute granulomatous (De Quervain's) thyroiditis: Fine-needle aspiration cytology and ultrasonographic characteristics of 21 cases

Background: Subacute granulomatous thyroiditis (SGT) is an inflammatory disease that presents with different clinical and cytological characteristics. Although the diagnosis is generally made clinically, imaging methods and fine-needle aspiration (FNA) may provide assistance, particularly in atypical cases. The objective of this study is to reveal the ultrasonographic (USG) and cytological characteristics of SGT. Materials and Methods: The clinical, USG and cytological findings of 21 cases diagnosed with SGT were reviewed. Results: Ultrasonographic data was available in 20 cases. A hypoechoic thyroid nodule with irregular margins was detected in 12 of the 20 total cases. Of these, 9 cases complained about pain in the thyroid lodge and generally had unilateral lesions, heterogeneous and hypoechoic areas with indistinct margins, rather than nodular lesions, which were seen in 7 cases. Cytologically, the multinuclear giant cells (MNGCs) found in all cases were accompanied by a dirty background containing varying numbers of granulomatous structures, including isolated epithelioid histiocytes, proliferated/regenerated follicle epithelium cells and inflammatory cells and colloid. Conclusion: Though hypoechoic and heterogeneous areas with irregular margins are strongly associated with thyroiditis, SGT may also appear as painful or painless hypoechoic, solid nodules and generate challenges in differential diagnosis. Although the most remarkable characteristic observed in FNA cytology was the presence of multiple MNGCs with cytoplasm, a dirty background accompanied by mild-moderate cellularity, degenerated-proliferated follicular epithelium cells, rare epithelioid granulomas and mixed type inflammatory cells are characteristic for SGT. The assessment of these radiological and cytological findings in conjunction with clinical findings will assist in the achievement of an accurate diagnosis.

Transthoracic fine-needle aspiration cytology of non-invasive, low-grade urothelial carcinoma with lung metastasis: A case report with review of the literature

Radiological analyses in a 61-year-old patient being followed since 2005 for low-grade, non-invasive urothelial carcinoma (UC) (Ta) revealed a 5-cm pleural-based mass in the lower lobe of the right lung for which a subsequent transthoracic fine-needle aspiration cytology was performed. Upon observing the carcinoma cells consistent with UC metastasis, systemic chemotherapy was commenced. The patient underwent a metastatectomy based on the thoracic computerized tomography scan performed on the 4th month of treatment, which revealed notable regression. The resected tumor was morphologically similar to cells seen in the transthoracic fine-needle aspiration and was immunohistochemically positive for p63, uroplakin, thrombomodulin, CK7 and CK20 at varying degrees but was negative for TTF-1. We report a case of metastatic UC of the lung in a patient who had had a low-grade superficial UC of the urinary bladder and we discuss the cytopathological features of this rare entity in light of the literature.

Amylase crystalloids in fine needle aspiration cytology of parotid gland: A diagnostic challenge

Sir, Several types of crystalloids may be seen in fine needle aspiration cytology of benign or malignant lesions of the salivary gland.[1,2] Due to their rarity, they may lead to confusion in diagnosis. Amylase type crystalloids (sometimes named nontyrosine crystals) are rarely found angular, nonbirefringent rectangular formed structures, with geometric shapes ranging between 5 μ and 500 μ in size and stained orange with Papanicolaou (PAP), dark blue with Diff-Quik® (DQ) and pink with Hematoxylin-Eosin (HE) stain. They were first defined in salivary gland cysts in 1983 by Takeda and Ishikawa.[1,3] Amylase crystalloids may also be observed in cystic sialadenitis as much as in cystic lesions.[1] We have presented here a case with cystic and chronic sialadenitis in the parotid gland, containing amylase crystalloids. The ultrasonographic assessment performed on a 58-year-old female patient who had applied with a complaint of swelling in the frontal part of the left ear and on the left part of the neck resulted in the detection of a lesion at a size of 12.5 mm × 11 mm in the lower zone of the left parotid [Figure 1] and lymph node at a diameter of 1 cm in the left cervical area. Figure 1 Ultrasonographic picture of the parotid mass Ultrasound-guided fine needle aspiration was performed by cytopathologist (N.P) with the preliminary diagnosis of the parotid tumor. About 0.2 cc of a mucoid fluid at an off-white color was aspirated. The slides were stained with DQ, PAP and HE. Cytologic findings showed mixed-type inflammatory elements, proliferated salivary gland acinar cells, reactive atypical salivary gland ductal cells as well as square, cuboid, needle, rectangular, rhomboid or bar-shaped crystalloids [Figure ​[Figure2a2a–d]. The crystalloids were stained bright orange with PAP; deep blue with DQ and eosinophilic with HE [Figure ​[Figure3a3a and ​andb].b]. Birefringence of the crystalloids was not observed by polarized light. The case was reported as cystic and chronic sialadenitis containing amylase crystalloids. The patient was monitored, and no growth was detected in the 2 years follow-up. Figure 2 Various cytologic images of the amylase crystalloids on different power and stains. (a) Diff-Quik®, ×100. (b) Diff-Quik®, ×200. (c) Papanicolaou, ×200. (d) H and E, ×400 Figure 3 Images of crystalloids at high power magnification with representative morphology. (a) Diff-Quik®, ×400. (b) H and E, ×400 Many crystals such as amylase, tyrosine, collagenous crystalloids, oxalate and intraluminal crystals may be observed in the fine needle aspiration smears of salivary gland lesions.[1,2,4] It is important to differentiate amylase crystalloids, which are geometric-shaped structures larger than 5 μm microscopically, from other crystalloids. Because, although crystalloids may be seen in malignant salivary gland tumors, amylase crystalloids accompany benign lesions.[1,5] The different types of crystals/crystalloids in relation to benign and malignant lesions and special stains/methods of detection are outlined below. Intraluminal crystalloids show a structure with geometrical shapes like amylase crystalloids. However, intraluminal crystalloids are dense, amorphous, filled with eosinophilic substance and at a size of 100 μ. Intraluminal crystalloid are reported to be seen in malignant salivary gland tumors.[6] Amylase crystalloids have more translucent appearance and are generally at a size of 500 μ. They are stained orange with PAP, dark blue with DQ® and pink with HE. Both intraluminal and amylase crstalloids are nonbirefringent. Amylase crystalloids are so far encountered with only in benign lesions including chronic sialadenitis, unilocular cysts, lymphoepithelial cysts and Warthins tumor.[1,7] Collagenous crystalloids are seen as radial and fusiform fibers of eosinophilic collagen on HE stain. These crystalloids stain bright blue on trichrome stain, indicating the presence of Type I collagen and are also positive on Snook Reticulin Stain, indicating the presence of Type III collagen. They are birefringent. Collagenous crystalloids are reported to be seen in pleomorphic adenomas, myoepitheliomas and also myoepithelial carcinomas.[5,6] Tyrosine crystals appear in an eosinophilic, refractile, flower-like shape with blunt ends (petal shaped) on HE stain. Tyrosine crystalloids are reactive with Millon reagent and are positive with diazotization-coupling reaction. They are nonbirefringent. Tyrosine crystals are mainly identified in pleomorphic adenomas and also rarely encountered in malignant salivary gland neoplasms such as carcinoma ex pleomorphic adenoma, adenoid cystic carcinoma, low-grade adenocarcinoma.[1,2,5,6] In conclusion, amylase crystalloids are not substances that may appear very frequently in parotid fine needle aspiration. They may accompany especially nonmalignant benign, chronic inflammatory lesions. They are rarely observed. We wanted to present our case in the light of literature for the purpose of highlighting the fact that crystalloids may lead to diagnostic challenges in parotid fine needle aspiration. We also focused on the representative cytomorphology of the crystalloids.

Solitary angiokeratoma of the tongue in an adult patient treated with intensity modulated radiation therapy.

A solitary mucosal angiokeratoma is an extremely rare presentation. In this report, we present a 67-year-old woman with a 3 cm solitary angiokeratoma involving the tongue, who was treated with intensity modulated radiation therapy after declining surgery. The patient is alive and free of disease at 1.5 years following radiation therapy.

Malignant tumors associated with ovarian mature teratoma: A single institution experience

OBJECTIVE The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. STUDY DESIGN Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. RESULTS A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. CONCLUSION An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach.

Perineural invasion is a valuable prognostic factor in advanced stage and/or Node (+) cervical cancer

Background: Perineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance cervical cancer remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes in clinically localized surgically treated cervical cancers. Materials and Methods: We reviewed clinical records and pathology slides of 111 patients with cervical cancer treated with surgery at a single academic center. PNI was evaluated for presence, number of foci per slide, involved largest nerve size, and topographically (intratumoral vs. extratumoral). Association with these parameters, clinicopathologic characteristics and survival were analyzed. Results: The analysis demonstrated that PNI in cervical cancer was significantly correlated with parametrial invasion, tumor size, resection margin involvement, lymphovascular invasion, lymph node (LN) metastasis, depth of stromal invasion, necrosis, and higher stage disease (P < 0.005). Similarly, PNI density and mean size of the nerve involved were also associated with advanced stage (P < 0.005). In the multivariate analysis, PNI was not an independent prognostic factor for disease-free and overall survival. However, in the advanced stage cases and LN (+) cases, PNI is significantly associated with lower overall survival (43 vs. 58 months and 36 vs. 60 months, respectively, P < 0.005). Conclusions: The presence of PNI is accompanied by high-risk factors for recurrence. Overall survival rate is significantly reduced in PNI (+) patients. Although PNI itself is not an independent prognostic factor, PNI has a significant prognostic impact on overall survival in patients with advanced stage and/or Node (+) cervical cancer.

Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer

Mullerian adenosarcoma following tamoxifen therapy is a rare condition. Our aim was to report the youngest patient in the literature with uterine mullerian adenosarcoma who was undergoing tamoxifen therapy for breast cancer. A premenopausal woman aged 38 years who was undergoing tamoxifen therapy for breast cancer, was admitted with symptoms of lower abdominal pain and irregular vaginal bleeding and malodorous vaginal discharge that had continued for at least 6 months. A pelvic examination revealed a large and malodorous polypoid mass protruding through the cervix and an enlarged uterus. A biopsy from the protruding polypoid mass was reported as a large area of necrosis with neoplastic mesenchymal cells. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvic-paraaortic lymph node dissection, and omentectomie. The histologic diagnosis was Mullerian adenosarcoma. As a result, she was discharged to the oncology department. The woman is alive and her chemoradiotherapy treatment is ongoing. The role of tamoxifen therapy in the development of endometrial neoplasms remains unclear, but all cases of endometrial thickening and vaginal bleeding must be investigated for Mullerian adenosarcoma in tamoxifen users.