[Combined presentation of autoimmune thyroiditis, bilateral papillary thyroid carcinoma, cervical thyrolipoma and diabetes mellitus]. / Az autoimmun thyreoiditis, a kétoldali papillaris pajzsmirigy-carcinoma, a nyaki thyreolipoma és a diabetes mellitus együttes elofordulása.

Thyrolipoma or thyroid adenolipoma is an extremely rare form of thyroid adenoma, which also contains mature adipose tissue and follicles covered with fibrous capsule. We present the case of the growing cervical lesion of a 52-year-old female with diabetes, which was removed during total thyreoidectomy. Autoimmune thyroiditis, bilateral papillary carcinoma and cervical thyrolipoma have been identified by the histopathological examination of the thyroid gland. Orv Hetil. 2018; 159(25): 1024-1032.

[Retrospective analysis of papillary thyroid microcarcinoma cases treated between 2001 and 2010 in the Hungarian National Institute of Oncology]. / Pajzsmirigy-mikrokarcinómás eseteink retrospektív áttekintése a 2001­2010. közötti idõszakban.

The standard treatment of papillary microcarcinomas (mPTC; ≤1 cm) regardless of their size, was similar to the advanced ones till the recent past: immediate surgery ± radioactive iodine (RAI) therapy. However, the American Thyroid Association (ATA) 2015 guidelines accept the active surveillance in selected cases. We performed a retrospective analysis on the clinical data of 103 patients with PTmC in a single (62.1%) or multiple nodes (37.9%), treated with immediate surgery followed in most cases by postoperative RAI between 2001 and 2010. N stage of the neck was pN0 in 81, and pN+ in 22 patients. Survival probability was significantly related to age (p<0.001), TSH level (p=0.0347), N stage (p=0.0402) and need for neck dissection (p=0.0045). Overall survival at 5, 10, and 15 years was 95%, 89%, and 86%, while disease-specific mortality at 5 and 10 years was 3% and 5%, respectively. Our data show that immediate radical surgery with or without postoperative RAI yielded long-term survival similar to those published. Nevertheless, progression affecting mostly older men was not prevented by immediate surgery. Our findings do not contradict the acceptability of active surveillance recommended by the 2015 ATA Guidelines.

[On-site fine-needle aspiration cytology of thyroid nodules. Quality assurance of the Bethesda System for Reporting Thyroid Cytopathology (2008)]. / Pajzsmirigygöbök vékonytu-aspirációs citológiai vizsgálata. A Bethesda-rendszer (2008) minoségbiztosítása.

INTRODUCTION: The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. AIM: The aim of this study was to determine the quality assurance of fine-needle aspiration cytology of thyroid nodules. METHOD: Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 1384 patient with thyroid nodule underwent fine-needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. CONCLUSION: The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values.

Clinical significance of sentinel lymph node involvement in malignant melanoma.

In the period 1997-2002, sentinel lymph node (SLN) surgery was performed on 179 primary skin melanoma patients, one to two months after the removal of the primary. Staining with patent blue was combined with an isotope technique. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph node was followed, preferably within 2-3 weeks, by regional block dissection. In these cases interferon-a2 in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14.7%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.00001). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007 respectively). Comparison of the tumor thickness and positive SLN by discriminance analysis, yielded 81.7% and 79.9%, respectively for correct classification rates. Based on our study and data from the literature, we suggest SLN-positivity as equally strong poor prognosis factor for skin melanoma as the tumor thickness.

[Different histological findings in two specimens from pulmonary metastasectomy in the same patient]. / Tüdómetastasectomia során eltávolított több góc különbözó szöveti szerkezettel.

INTRODUCTION: Out of the 3310 thoracic surgical procedures performed between 1980 and 2000 at the Department of Surgery of the National Institute of Oncology in Budapest, 258 were pulmonary metastasectomies involving 236 patients. Primary tumors were the following in order of decreasing frequency: testicular cancer, colorectal cancer, renal cancer, soft tissue tumor, breast cancer and others. METHODS: In the present study the authors report two patients with multiple pulmonary metastases. The primary tumor was non-seminoma testicular cancer in case one and endometrial cancer in case two (previously treated for thyroid cancer). Histological examination of resected specimens revealed unsuspected focal inactive tuberculosis in the first case and medullary thyroid cancer in the second. CONCLUSIONS: In the reported two cases the following conditions of metastasectomy were given: 1. satisfactory cardiopulmonary status, 2. possibility of surgical radicality, 3. locoregional disease control, 4. prior chemotherapy in chemosensitive tumor (case one). The generally accepted condition of metastasectomy-lack of clinically manifest disease in other distant organs--was not fulfilled in case two (suspected liver metastases).

[Expression of oestrogen receptor-beta in invasive breast tumours]. / Az ösztrogénreceptor-béta expressziója invazív emlôtumorokban.

UNLABELLED: Steroid hormone receptors are used routinely to predict endocrine responsiveness in patients with breast cancer. Two oestrogen receptors (ERs): ER alpha and ER beta have been identified. Although ER alpha and ER beta genes share a large degree of homology, it is generally thought that their distribution and function are substantially different in many tissues. Both of them may be expressed in normal and neoplastic tissues of the breast. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. Recent development of reliable antibodies to ER beta has provided opportunity to test immunohistochemical reactions detecting ER beta in archival breast tumours. The aim of our study was to learn more about the cellular mechanisms underlying the relationship of ER beta and progesterone receptor (PR) in breast cancer tissues, discriminating between hormone-dependent and hormone-independent tumours. ER alpha and PR content of tumour tissues of 154 patients with breast cancer were tested by in situ indirect immunohistochemical method parallel with ligand binding biochemical assay. ER beta was detected in 8 ER alpha-/PR+ breast carcinomas by immunohistochemical method too. Steroid hormone receptor content was analysed comparing to the histologic type and grading of the tumours. CONCLUSIONS: A considerable part of breast carcinomas belongs to the ER+/PR+ and ER-/PR- groups. About 1-2% of the tumours is expected to be ER alpha-/ER beta+/PR+ type. In such cases ER alpha negative reaction together with PR positivity can signal the necessity of the immunohistochemical detection of ER beta in routine histopathological practice, presenting the precise steroid hormone receptor status for the most effective endocrine therapy of the patients.

[Angiocentric T-cell lymphoma] / CD20+ angiocentrikus T-sejtes lymphoma.

SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of T-cell lymphomas that present cystic changes in organs because of ischaemic necroses. The purpose of this study was to describe a case of CD20+angiocentric T-cell lymphoma, discussing its clinical, histopathological and immunohistochemical features, to analyze its proliferation kinetics and to consider its possible relationship to the Epstein-Barr virus (EBV) to understand better the pathobiological nature of the disease. METHODS: The clinical, histopathological, immunohistochemical and single-cell DNA cytophotometric features of the case were analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS: The 24 years old woman was admitted to our Institute because of pain in the abdominal region and weight loss. There were enlarged lymph nodes on the neck, and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+ variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2 phase: 7.6%. Combined chemotherapy was administered because of clinical stadium IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease showed gradual progression and the patient died 14 months after the first symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its clinical symptoms are special, the prognosis is unfavourable. The cause why we demonstrate this case is to call attention to a new treatment for these patients by immunotherapy using monoclonal antibodies against CD20 antigen.

[Preoperative lymphoscintigraphy guided sentinel lymph node biopsy in malignant melanoma] / Preoperatív limfoszcintigráfiával végrehajtott sentinel nyirokcsomó mûtétek melanoma malignumban.

The authors present preliminary experience with preoperative sentinel lymph node biopsy carried out with lymphoscintigraphy in patients with malignant melanoma. PATIENTS AND METHODS: In the present study patients operated for primary cutaneous malignant melanoma of moderate and high severity were included. On the day of surgery isotope labelled colloid was injected intradermally around the tumor to indicate the lymphatics and to obtain basic information about the localization of the sentinel lymph node(s).During surgery the lymph node(s) previously visualized by the injection of patent-blue staining were detected with the aid of a gamma probe. Simultaneously, the excision of the primary tumor was extended. Histologically verified metastasis in the surgically removed lymph node(s) necessitated block dissection possibly within two weeks. RESULTS: The distribution of patients (19) according to tumor localisation: 2 - upper extremities; 9 - lower extremities; 2 - sacral region; 6 - trunk. Tumor thickness ranged from <1.5 mm (6 patients) to 1.5-3 mm (5 patients) and to >3 mm (8 patients). In two cases the identification of the lymph node has failed. Positive sentinel ymph nodes were detected in two patients. It is noteworthy that with one patient the sentinel lymph node was not regional but intransit. This study was aimed at the development of a suitable method. Further on we wish to try it in prospective randomized studies.

[Prognostic factors of breast cancer] / Emlôdaganatok prognosztikai faktorai.

OBJECTIVES: Characterization of breast cancers by various tumour markers which are appropriate for the identification of high risk groups. Markers related to the metastasis cascade and tumour recurrence have been investigated. MATERIALS AND METHODS: RT-PCR was used to determine the expression of cytokeratin 20 in the bone marrow and sentinel lymph node of breast cancer patients (n=45). The expression of HER2, Cadherin E, Cyclin D, Bcl2 and Bax has been evaluated by Western blot (n=744 invasive ductal carcinomas and 117 invasive lobular carcinomas, 124 recurrent breast cancers). Mutations of p53, APC and beta Catenin genes were detected by PCR-SSCP method. RESULTS: Expression of cytokeratin 20 was found in 30% of the bone marrow samples indicating the presence of micrometastasis. The level of Cyclin D, HER2 and Bcl2 is elevated four-fold in the recurrent breast cancers. The metastasis of invasive ductal carcinomas is accompained by high frequency of p53 mutations (24%) and APC mutations (18%). The invasive lobular carcinomas could be characterized with low frequency of p53 mutation (3%), low level of Cadherin E and high level of catenin beta. CONCLUSIONS: Identification of micrometastasis can promote the development of therapeutic strategy. Evaluation of HER2 level and determination of p53 mutations contribute to the identification of high risk patients. Our results suggest that the progression of invasive ductal carcinomas depends on the APC mutations, while metastasis of invasive lobular carcinomas depends on beta catenin mutations.

[Report on clinical observations obtained with sentinel lymph node surgery in malignant melanoma and during their follow-up at the Department of Dermatology, National Institute of Oncology, Budapest]. / Sentinel nyirokcsomó-biopszia melanomában. Klinikai tapasztalatok az Országos Onkológiai Intézetben.

OBJECTIVES: Report on clinical observations obtained with sentinel lymph node surgery for malignant melanoma and during follow-up at the Department of Dermatology, National Institute of Oncology, Budapest. PATIENTS AND METHOD: In the period from November, 1997 to September, 2002, the above surgical intervention was made with 179 patients having primary tumour, one to two months after primary tumour removal. Staining with patent blue was combined with isotope technique. The primary melanoma and the pertaining sentinel lymph node(s) were removed. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph nodes was followed, preferably within 2-3 weeks, by regional block dissection. Interferon in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. RESULTS: Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.0000). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007, respectively). In the discriminance analysis of our data, the discriminant function established from tumour thickness yielded 81.7% and the positivity of sentinel lymph nodes 79.9% correct classification rates. CONCLUSION: In good harmony with literature data, positive sentinel lymph node(s) were found in the case of thicker tumours. The involvement of sentinel lymph node indicated a significantly poorer prognosis.

[Clinical significance of serum thyroglobulin and antithyroglobulin antibody in differentiated thyroid cancer after thyroid ablation]. / Szérum thyreoglobulin és thyreoglobulinellenes antitest meghatározásának klinikai jelentôsége pajzsmirigyrákkal mûtött betegek vizsgálata során.

Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma following total thyroid ablation. Between 1998 and 2003, serum samples from 715 papillary and 179 follicular tumor patients treated with total/nearly total thyroidectomy and radioiodine ablation therapy were collected. According to the "Guidelines for Oncotherapy in Hungary", serum Tg, antithyroglobulin antibody (TgAb), TSH and FT4 levels were measured in periods of 3 months following the first treatment and of 6 months after 2 years. In the present work the prognostic value of Tg and TgAb data of cancer patients with hormone substitution therapy were evaluated individually and retrospectively. Serum Tg and TgAb concentrations were measured with a highly sensitive immunoradiometric (IRMA) method, and with a second generation, broad epitope specificity competitive radioimmunoassay, respectively. TSH levels determined by fourth generation LIAISON kit were in a range of 0.05-0.10 mIU/L. Accuracy of measuring of Tg <1 ng/ml made it possible to select the low cut-off level (Tg <2 ng/ml) following total thyroidectomy. In the predominant part of TSH-suppressed patients (746/774, 96%) the serum Tg concentration was below the cut-off level of 2 ng/ml. The sensitivity of Tg determination in 59 TSH-suppressed thyroid cancer patients with lung and bone metastases was as high as 86 to 100%. On the contrary, the number of false negative data was high in cases with lymph node metastases of papillary cancer, and sensitivity did not exceed 62%. Specificity and sensitivity of Tg in TgAb negative patients were 91 to 100%. Based on our results it could be concluded that measuring of Tg and TgAb, using a current IRMA method and a second generation RIA kit, proved to be effective tools for the postoperative monitoring of differentiated thyroid tumours. It has to be noted that determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. Persistently high and/or increasing serum TgAb concentration with low Tg result had a diagnostic value during the follow-up and can be connected with the recurrence or persistence of the differentiated thyroid cancer.

High expression of claudin-1 protein in papillary thyroid tumor and its regional lymph node metastasis.

Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of beta-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by beta-catenin in thyroid tumors. Based on these results, claudin-1 may be a useful tumor marker for PTC.