Radioguided occult lesion localisation in combination with detection of the sentinel lymph node in non-palpable breast cancer tumours.

PURPOSE OF THE INVESTIGATION: The aim of study was to determine the efficacy of radioguided occult lesion localisation (ROLL) for non-palpable invasive breast cancer combined with sentinel lymph node biopsy (SLNB) and to compare the amount of tissue excised by radioguided navigation versus the hook-wire technique. METHODS: We injected 45 MBq of radiolabelled technetium intratumourally and 15 MBq subdermally 18 hours before surgery in 21 women with bioptically verified non-palpable breast cancer. We identified by gamma probe non-palpable tumours, which were excised, followed by identification and excision of the sentinel lymph node. We compared our results with a group of 12 women with non-palpable lesions marked by hook-wire localisation. RESULTS: ROLL combined with SLNB was successful in 100%; volume of excised tissue was smaller in the hook-wire group but expressed higher variability in volume than in the ROLL group although the difference was not statistically significant. CONCLUSION: The method of ROLL combined with SLNB is technically possible and safe, resulting in minimisation of the surgical intervention and a decrease in postoperative morbidity. ROLL was more precise than the hook-wire procedure even though the amount of tissue excised was the same in both groups.

[New method for detection of nonpalpable breast cancer]. / Nová metoda detekce nehmatných karcinomu prsu.

OBJECTIVE: The objective of the study was to evaluate the feasibility of radio guided occult lesion localization (ROLL) in the cases of nonpalpable breast cancers with sentinel lymph node biopsy. DESIGN: Prospective clinical study SETTING: Department of Gynecology and Obstetrics, 2nd Medical Faculty and Teaching Hospital, Praha METHODS: Thirty-eight patients with nonpalpable breast cancer diagnosed by core cut biopsy underwent an injection of the radiopharmaceutical 18-20 hours before surgery. The dose of the radiopharmaceutical was 45 MBg into tumor and 15 MBg subdermaly. Surgical excision of radioactive breast tissue with nonpalpable tumor was carried out using the hand held gamma probe and the same technique was performed for biopsy of sentinel lymph node. Standard localization technique with hook-wire was performed in the control group of fifty-one patients. RESULTS: Radioguided surgery of nonpalpable tumor was successful in all cases. Surgical margins were clear in all cases, in four cases (10.5%) the margins were only 2 mm. The sentinel node was identified in all cases, in 3 patients (7.9%) the sentinel node was involved by tumor and axillary lymphadenectomy was performed. Infiltrating carcinomas were diagnosed in the "hook-wire" group in 21 cases (41.2%), all with clear margins over 3mm. Proportion of margins status between ROLL and hook-wire was the same. It seems that the health tissue loss around the tumor is in hook-wire technique bigger but it requires next study. CONCLUSION: Simultaneous performance of ROLL and sentinel node biopsy is useful and practicable methods in the management of nonpalpable breast cancer. In comparison to hook-wire, radioguided removal allows reduced excision volume and better lesion centering within the specimen.

[Sentinel lymphatic node biopsy for breast cancer in practice]. / Biopsie sentinelové lymfatické uzliny u karcinomu prsu v praxi.

OBJECTIVE: This paper reviewed the feasibility and accuracy of sentinel lymph node status in women with breast cancer. DESIGN: Clinical retrospective study. SETTING: Dept. of Obstetrics and Gynecology, 2nd Medical School, Teaching Hospital Motol, Praha. METHODS: Our trial involved 169 patients with breast cancer in the T1 and T2 stage without suspicion for axillary lymph node involvement. Lymphatic mapping was performed by sub dermal or subareolar injection of 99mTc labeled collodial human albumin (Senti-Scint) in the dose of 15 MBg one day before surgery. During the operation lymphatic mapping with vital blue dye (patent blau) was performed. Then the hand-held gamma-ray detector probe was used to locate the sentinel node. From a small axillary incision the blue-stained sentinel node was removed. Both methods of detection were compared, the sentinel lymph node has to be hot-radioactive and blue-stained. Complete axillary lymphadenectomy was then done. All removed lymph nodes were prepared for histopathological examination. RESULTS: Failures of sentinel lymph node detection were in 9 cases (5.3%) of the 169 patients. There was one case of false negative sentinel lymph node biopsy (0.6%). Most failures occurred during the learning phase of lymphatic mapping and were associated with excessive tumor involvement of axillary lymph nodes. Success of sentinel lymph node detection was in 160 cases (94.7%) and in our trial both methods of lymphatic mapping were equally effective. Tumor involvement of sentinel lymph nodes were in 43 patients (26.9%), in 19 (11.9%) of them, the sentinel nodes were the only metastasis nodes, whereas in the remaining 24 (15%) patients other axillary nodes were positive. The concordance between negative sentinel node and axillary lymph node status was in 117 (73.1%) cases. CONCLUSION: The introduction of sentinel lymph node biopsy allows directed and accurate assessment of axillary involvement with minimal morbidity. Sentinel node accurately predicts the status of all axillary nodes in more than 94.7% of cases.

[Mixed germ cell tumours of the ovary in childhood and adolescence]. / Smísené germinální nádory ovaria u detí a dospívajících. Retrospektivní klinicko-patologická studie.

Mixed germ cell tumours of the ovary are rare malignant neoplasms containing combinations of two or more types of germ cell elements. The aim of the study was to review biopsy examinations, medical records, treatment strategy, follow-up and outcome of all girls treated for mixed germ cell tumour of the ovary at the Department of Pediatric Oncology, University Hospital Motol during the period 1979-2002. Archival slides of all tumours were reviewed and tumours were classified according to the WHO system. The clinical data on surgical treatment, chemotherapy and radiotherapy used and follow-up information were obtained in all girls. The staging was reviewed retrospectively on the basis of surgical and pathological findings and results of imaging investigations, and it was outlined according to the most recent FIGO criteria and TNM classification. Sixteen girls with mixed germ cell tumour of the ovary, age range 3 years 11 months to 17 years 8 months (median 12 years) were treated. All girls presented with unilateral tumour of the ovary and all underwent surgery as an initial treatment. The most common presenting symptom was abdominal pain, occurring in ten patients. The original diagnosis of mixed histology was confirmed in all cases; in five cases the tumour contained three histologic components, in eleven cases the tumour consisted of two germ cell types. All tumours contained elements of yolk sac tumour, followed by immature teratoma, embryonal carcinoma, dysgerminoma and mature teratoma. At the time of diagnosis three patients had stage I disease, four patients stage II, seven stage III and two stage IV disease. All patients were treated with chemotherapy after surgery, predominantly with platinum-based regimens (PVB, BEP). Three patients treated initially with MAC (metothrexate, dactinomycin, cyclophosphamide) were diagnosed in the early eighties. In seven girls with advanced disease treated in the early years, radiotherapy was administered to the pelvis or whole abdomen. Overall survival and event-free survival were 80% and 81.3% respectively (median follow-up time 7.6 years). Three patients have died from the disease, two progressed on treatment (MAC), one girl relapsed three months after finishing therapy, no further therapy was administered. One girl underwent resection of tumour of her remaining ovary 24 months after original diagnosis. Histology showed mixed serous and mucinous cystadenoma. The latest examinations revealed that all other patients were in good health. Microscopic examination should be extensive and careful to find out all types of malignant germ cell elements. Platinum based chemotherapy is effective in the management of children and adolescents with mixed germ cell tumors of the ovary. Chemosensitivity of these tumours allows most girls to have conservative surgery with possible preservation of reproductive function.

[Ovarian dysgerminoma in children and adolescents. Retrospective clinico-pathologic study]. / Dysgerminomy ovaria u detí a dospívajících. Retrospektivní klinicko-patologická studie.

BACKGROUND: To review the treatment strategy, follow up and outcome for all patients with pure ovarian dysgerminoma treated in childhood and adolescence. METHODS AND RESULTS: Twenty-one patients younger than 18 years were treated between 1979-2002 in Faculty Hospital Motol for newly diagnosed pure ovarian dysgerminoma. Patients were included into the cohort on the basis of revision of archival biopsy specimens deposited in Institute of Pathology and in Molecular Medicine tumor registry. The staging was reviewed retrospectively on the basis of surgical and pathological findings and on results of imaging investigations and outlined according to the TNM and International Federation of Gynecology and Obstetrics (FIGO) classification. The median age at the time of diagnosis was 12.5 years (range 6 years, 5 months--17 years, 11 months). There were ten FIGO stage IA tumors, one stage IB, two of stage IIC, one stage IIIB and seven IIIC tumors. All patients, except two girls with bilateral dysgerminoma, underwent unilateral adnexectomy or ovarectomy. Ten girls were treated postoperatively with chemotherapy, eight with chemotherapy and radiotherapy (eleven with cisplatine based chemotherapy). Three girls with dysgerminoma confined to the ovary (stage IA) have not received adjuvant chemotherapy. With a median follow up 7.1 years all girls remained continuously disease free. The 5-year overall and event free survival is 100%. Majority of patients does not have severe treatment sequelae, three pregnancies have occurred so far. CONCLUSIONS: Most patients with dysgerminoma, including those with metastases can expect cure when treated with conservative surgery and cisplatine based chemotherapy. Reduction of treatment toxicity and preservation of reproductive function is a main task. The girls with dysgerminoma confined to the ovary (stage IA) can be treated with fertility sparing surgery, other should be treated with cisplatine based chemotherapy.

Detection of the sentinel node in breast carcinoma using method of a single subcutaneous injection of radiopharmaceutical.

The objective of this work is retrospective evaluation of results of the intraoperative detection of sentinel node in breast carcinoma after a single subcutaneous injection of radiopharmaceutical (RF) within a two-day protocol. From May/2001 to June/2002, lymphoscintigraphy of the sentinel node (SN) and its subsequent radioguided intraoperative detection (RGS) was performed in 43 women having stage T1-T2, N0 breast carcinoma. The static scans in the anterior and relevant lateral projections were performed using a gamma camera at approximately 30-minute intervals after the subcutaneous administration of 15 MBq 99mTc Senti-Scint, until the SN was displayed. The localization of the SN was marked on the overlying skin with a water-resistant permanent marker in 1-2 projections. RGS was accessed within 18-24 hours after the injection of the RF and all patients underwent an axillary dissection. The SN was detected in all patients, and in all cases was localized in the ipsilateral axilla. In 26 patients (60%), no metastatic process was found either in the SN or in any other axillary node. However, in one node, deposits of the carcinoma were detected in surrounding fatty tissue with propagation along the vessels and nerve. In 16 patients (37%), metastases in the SN were proved, in 7 cases (16%), a metastatic process was proved at the same time even in further lymph nodes. A number of false negative findings (5.8%) is consistent with the literature data. The method fails in the detection of intramammary localized SNs.

[Hormone replacement therapy, proliferation in the breast and risk of carcinoma]. / Hormonální substitucní lécba, proliferace prsu a riziko karcinomu.

OBJECTIVE: The objective of the study was to investigate the changes of histopathological and immunohistochemical parameters of breast tissue among the HRT users. DESIGN: Prospective, pilot study. SETTING: Departments of Gynecology and Obstetrics, Pathology and Radiology of the 2nd Medical School, Charles University and the Teaching Hospital Motol, Praha 5, Czech Republic. METHODS: The samples of breast issue were obtained by core cut biopsy and during the breast surgery procedures in the study group of HRT users (no = 48) and in the control group of women without HRT (n = 22). Proliferation index (Ki-67), expression of ERB2 oncoprotein and hormonal receptors (ER, PR) were examined in the breast tissue in addition to routine histopathological examinations. RESULTS: We did not record increasing frequency of proliferative and precancerous lesions in the group of HRT users. Ki-67 expression was very low both in HRT users and in the control group of women. The values of estrogen receptors expression in breast tissue samples of women with HRT were similar to the findings in the normal breast. The values of progesterone receptor expression were higher among the HRT users then non-users, but it can be considered as a normal response of breast tissue to hormonal influence. Expression of ERB protein in HRT users was similar to that found in non-users. CONCLUSION: The findings indicate that HRT has not increased the proliferation rate of the breast tissue in our study group, so this mechanism certainly does not increase the risk of breast cancer.

[Superficial epithelial-stromal ovarian tumors in girls]. / Povrchové epiteliálne-stromální nádory ovaria u dívek.

Superficial epithelial-stromal ovarian tumours are unusual in adolescent girls (when compared with adult women) and extremely rare before menarche. A group of 40 girls with such tumours was chosen among 180 cases (22%) of ovarian tumours in childhood and adolescent age. All of them were between 9 and 18 years with one exception of a 5-year old girl. Mucinous tumours (22 cases) prevailed a bit over the serous ones (16 cases), two tumours were seromucinous. 35 tumours were one sided, 5 bilateral belonged to serous tumours. One sided tumours comprised 5 cystadenomas, 5 cystadenofibromas and 1 borderline serous tumour. Bilateral neoplasms were represented by 3 serous cystadenofibromas, 1 borderline serous tumour and 1 serous cystadenocarcinoma. Mucinous tumours comprised 16 benign cystadenomas, 4 borderline intestinal type tumours (one with identifiable eosinophilic indifferent cells) and 2 mucinous intestinal type cystadenocarcinomas. Both mixed tumours had the structure of seromucinous cystadenoma.

[Parovarian cysts and tumors in adolescent girls]. / Parovariální cysty a nádory u dospívajících dívek.

Biopsy in 30 girls suffering from parovarial lesions showed 27 parovarial cysts and 3 parovarial tumours. Girls' age varied between 12 and 17--except an 1-year-old infant. 13 girls had to be operated on paramesonephric unilocular usually solitary cysts with a tubal sort of lining. 4 girls had simultaneous paramesonephric and mesonephric cysts which were bilateral in two cases. Pure mesonephric cysts were found in further 9 patients combined with other bioptic lesion; they were microscopical and character of their lining was that of dilated mesonephric ducts. Only one cyst which had to be operated on had mesothelial lining in all sections. Parovarial tumours were bilateral in one patient--a serous papillary cystadenoma followed later by serous cystadenofibroma; other 2 patients had serous cystadenofibroma and borderline serous papillary cystadenoma. Neoplastic nature of the last 3 lesions was not established until the biopsy.

[Histological structure of the peniform clitoris in congenital adrenogenital syndrome]. / Histologická struktura peniformní klitoridy pri kongenitálním adrenogenitálním syndromu.

Peniform clitoris in 50 girls suffering from congenital adrenogenital syndrome were subtotally removed at the age of 4-6 years and studied by biopsy. A corpus spongiosum more or less developed was found in all cases beneath the corpora cavernosa in the bottom part of corpus clitoridis, epithelial urethral rudiments represented by single or multiple short tubules with transitional epithelium and mucinous glands were found in 46 cases; they were localized in corpus spongiosum or close to it in loose connective tissue. Other urethral rudiments occurring in glans clitoridis were represented by long slight pegs of squamous epithelium extending into corpus spongiosum glandis. Control samples from 20 4-6-year-old girls who had deceased from tumours showed but once heterotopic epithelial urethral rudiments-tubules with transitional epithelium and mucinous glands.

Fatal infantile hypertrophic cardiomyopathy secondary to deficiency of heart specific phosphorylase b kinase.

We describe here a male infant with a rare form of glycogenosis caused by deficiency of heart specific phosphorylase b kinase. The disease phenotype was characterized by severe glycogenosis restricted to the heart muscle with secondary rapidly progressive hypertrophic cardiomyopathy causing death at the age of 47 days.

[Juvenile granulosa cell tumor with subsequent occurrence of gastrointestinal polyposis, subcutaneous lipomatosis and nodular goiter]. / Juvenilní nádor z bunek granulózy s následným výskytem polypózy zazívacího traktu, subkutánní lipomatózy a nodózí strumy.

A juvenile tumour from granulosa cells (M-8622/1), 13 x 8 x 6 cm, in the right ovary in a three-month-old girl produced some symptoms of pseudopubertas praecox isosexualis which disappeared after operation. Microscopic examination of the tumour revealed in addition to typical structures a less common differentiation to Sertoli cells. Despite actinotherapy and chemotherapy one and a half years after the onset of the disease X-ray examination revealed metastases in the lungs which were successfully cured by further doses of the above two types of treatment. Between the age of 6 and 15 years the girl developed successively polyposis of the stomach, small and large intestine (M-7564/0), subcutaneous lipomatosis of the trunk and left lower extremity (M-8881/0) and nodular goitre (M-7164/0), predominantly quiescent. In the literature a connection between gonadal stromal ovarian tumours and mesenchymal tumours, intestinal polyposis and disorders of the thyroid gland is described, but in different patients. The authors' observation is unique by the successive incidence of these changes in a single patient surviving 15 years after operation; and thus genetically conditioned associations could be involved.

[An ovarian tumor with structural gonadoblastoma, dysgerminoma and choriocarcinoma]. / Ovariální nádor se strukturami gonadoblastomu, dysgerminomu a choriokarcinomu.

A 14 1/2-year old girl with menometrorrhagia followed by amenorrhea and abdominal pain had a pelvic resistance with limited mobility. Histology of a left ovarian tumour showed gonadoblastoma turning to dysgerminoma and associated with choriocarcinoma (M-9073/1, M-9060/3, M-90101/3). Genuine ovarian tissue was hypoplastic on both sides. In the right ovary, there were additional thecalutein cysts. The patient's karyotype was 46 XX. She has been without any relapse 2 1/2 years after chemotherapy and actinotherapy.

Mixed germ cell-sex cord stromal tumor with heterologous structures.

A mixed germ cell-sex cord stromal tumor developed in the right ovary of a 4-year-old girl. The patient's cells contained sex chromatin and the karyotype was 46,XX. Clinically, she exhibited mild isosexual pseudopuberty. Some of the tumor cells showed differentiation to Sertoli cells, whereas others had characteristics of germ cells. The neoplasm was composed of solid cords consisting of a mixture of the two tumor cell types and surrounded by a delicate connective-tissue network. In one small area, the tumor contained heterologous development in the form of glands and cysts lined by columnar mucinous epithelium containing numerous goblet cells and occasional argyrophilic neuroendocrine cells. Normal ovarian tissue was present at the periphery of the tumor. Electron microscopic study confirmed the presence of both Sertoli-like and germ cell-type cells. Immunohistochemical studies demonstrated vimentin positivity in both cell types (with preference for the Sertoli-like cells) and cytokeratin positivity in the Sertoli-like cells. The patient was symptom free 4 years after right oophorectomy, radiotherapy, and chemotherapy.

[Gonadal dysgenesis]. / Gonadální dysgeneze.

The authors describe six patients, female phenotype with karyotype 45X/46XY. Two girls suffered from pure gonadal dysgenesis, four from mixed gonadal dysgenesis. The authors emphasize the intact axis hypothalamus-pituitary gonads. In the above diagnoses the authors recommend revision and extirpation of the gonads with regard to possible malignant growth in the dysgenetic gonad.

[Juvenile granulosa cell tumor]. / Juvenilní nádor z bunek granulózy.

Granulosa cell juvenile tumours, defined in 1976 by Scully as a separate unit are found mostly in girls during the first two decades of life. On inspection under an optic microscope they are characterized by the presence of non-differentiated "blastemoid" structures and the formation of solid follicular formations and cysts. In our first case we observed a bilateral juvenile tumour made up of granulosa cells in a 8-month-old girl where the tumour produced symptoms of pseudopubertas praecox isosexualis. In the second case in a 9-month-old girl also with symptoms of pseudopubertas praecox isosexualis the authors detected in the left ovary a tumour which probably is a less differentiated variety of the juvenile granulosa cell tumour. These tumours belong into the group of little differentiated gonadal-stromal tumours with ICD-O code M-8590/1.

[Ultrastructure of foamy and pigmented cells in the female breast]. / Ultrastruktura penitých a pigmentových bunek v mlécné zláze zen.

Electronmicroscopy was performed on 5 surgical specimens from the mammary gland of 21-, 34-, 49-, 49-, and 51-years-old women. Histological diagnosis of mammary dysplasia was established in all of patients. Ultrastructure of foamy cells showed lipid vacuoles without obvious limiting membrane, lysosomal vacuoles with annulate and vesiculate membranous structures, lamellar bodies and lipofuscin inclusions which prevailed in pigmented cells. There were only quantitative differences between both types of cells. Neither phagocytosis nor another feature of macrophagic origin were found. On the contrary, epithelial origin of these cells could be conceded according to the finding of desmosomes among foamy cells in ductal lumina. But periductal cells apparently could be derived from stromal cells.