Imaging of gynecological disease (4): clinical and ultrasound characteristics of struma ovarii.

OBJECTIVES: To describe the clinical history and ultrasound findings in women with struma ovarii. METHODS: Women with a histological diagnosis of struma ovarii who had undergone preoperative ultrasound examination were identified from the databases of five ultrasound centers. The tumors were characterized on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, four authors reviewed all ultrasound images and described them using pattern recognition. RESULTS: Of 31 patients identified, 16 had pure struma ovarii (one malignant), whereas in 15 patients the struma ovarii were 'impure', constituting the major part of a dermoid cyst (all benign, bilateral in one case). Median age was 40 (range, 18-80) years and 22 (71%) patients were of fertile age. Thirteen patients (42%) were asymptomatic, nine (29%) presented with pain, six (19%) with bloating, two (6%) with irregular bleeding and one (3%) with thyreotoxicosis. Most pure struma ovarii (11/16 cases, 69%) contained solid components, but cystic components were always present. The color content at Doppler examination varied from none to abundant. Four patients had ascites. Using pattern recognition the most specific feature of pure struma ovarii was the 'struma pearl', i.e. a smooth roundish solid area, similar, but not identical, to the 'round white ball' seen in dermoid cysts. 'Struma pearls' were present in six cases of pure struma ovarii. Most (10/16, 63%) cases of impure struma ovarii manifested ultrasound features compatible with a dermoid cyst, but six manifested ultrasound features similar to those of pure struma ovarii, 'struma pearls' being seen in three of these. CONCLUSIONS: The sonographic features of struma ovarii vary. Struma ovarii may be suspected when a 'struma pearl' is seen. Whether 'struma pearls' are indeed a specific ultrasonographic feature of struma ovarii needs to be determined in a prospective study.

Chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism.

Two cases of chronic parathyroiditis associated with parathyroid hyperplasia and hyperparathyroidism are described. There was no evidence of an underlying infectious disease, a developmental anomaly, or a drug reaction that could explain the inflammatory component. It is suggested that an autoimmune process might have been involved in the pathogenesis of this previously unreported clinicopathologic entity.

Histochemical demonstration of estrogen and progesterone binding in endometriotic tissue and in uterine endometrium: A comparative study.

Estrogen and progesterone binding to endometriotic and endometrial tissue was studied histochemically using estradiol and progesterone fluorochrome derivatives (E2-bovine serum albumin-fluorescein isothiocyanate and progesterone-bovine serum albumin-tetramethylrhodamine isothiocyanate). Thirty endometriotic samples from 21 women were studied, together with endometrial specimens obtained simultaneously from 14 of the women. In 77% of the endometriotic samples binding of the estrogen conjugate was indicated by specific fluorescence in more than half of the epithelial cell population, and in 20% in less than half. The corresponding figures for the progesterone conjugate binding were 75 and 18%, respectively. Blocking studies indicated a reasonable degree of ligand specificity. In endometrial tissue the corresponding figures were 64 and 29%, respectively, for binding of the estrogen conjugate and 54 and 38%, respectively, for binding of the progesterone conjugate. In 7 of 13 cases where evaluable samples of both tissues had been obtained, the relative proportion of fluorescent cells, with either reagent, was similar in the two tissue types. Our results suggest that the cytoplasm of epithelial cells in endometriotic tissue and in uterine endometrium contains specific binding sites for both estrogen and progesterone. The binding pattern of the two conjugates in endometriotic tissue was unrelated to the menstrual phase.

Histochemical localization of estrogen and progesterone receptors: evaluation of a method.

A histochemical method for the detection of estrogen (ER) and progesterone (PR) receptors in human endometrium, using estrogen and progesterone derivatives linked to fluorochrome-labeled bovine serum albumin (E2-BSA-fluorescein isothiocyanate (FITC) and progesterone-BSA-tetramethylrhodamine isothiocyanate (TMRITC], has been evaluated. The fluorochrome-labeled steroids were bound to the cytoplasm--preferably in glandular epithelial cells but to a lesser extent also to stromal cells. The steroid specificity of the observed binding was studied by preincubating the sections with a series of unlabled steroids and nonsteroidal, hormonally active compounds (estradiol-17 beta, diethylstilbestrol, tamoxifen, 5 alpha-dihydrotestosterone and R 1881 for ER and ORG 2058, R 5020, dexamethasone, cortisol and 5 alpha-dihydrotestosterone for PR). The inhibition studies indicated that E2-BSA-FITC and progesterone-BSA-TMRITC bind to ER and PR in human endometrium with a reasonable degree of specificity. The method was reproducible and various procedural steps were tested, showing satisfactory technical stability. The method is applicable to small tissue samples, and is a valuable complement to quantitative biochemical receptor assays, as it localizes the receptors in tissue slices.

Joubert syndrome associated with Leber amaurosis and multicystic kidneys.

We describe a boy with manifestations of Joubert syndrome, Leber congenital amaurosis, and multicystic kidneys. In infants with unexplained neonatal tachypnea and late developmental delay, absence or hypoplasia of the cerebellar vermis should be sought. Joubert syndrome probably is an autosomal recessive disorder. In the subsequent pregnancy of the propositus' mother, we were able to make a prenatal diagnosis of Joubert syndrome, one of the first to be reported.

Differentiated thyroid carcinoma, intermediate type: a new tumor entity with features of follicular and parafollicular cell carcinoma.

A group of differentiated thyroid carcinomas with morphologic and immunohistochemical traits of both follicular and medullary carcinoma is described. This group consists of tumors characterized by a solid and/or cribriform histologic pattern with a more or less pronounced admixture of follicular structures, immunohistochemical evidence for the production of thyroglobulin and one or more of the three neurohormonal peptides neurotensin, somatostatin, and calcitonin, and absence of amyloid. These tumors were selected from thyroid carcinomas that had been diagnosed, according to current histopathologic criteria, as differentiated follicular carcinomas. A series of pure follicular carcinomas, devoid of solid or cribriform structures, was found to contain thyroglobulin immunoreactive tumor cells only, whereas a series of classic medullary carcinoma with amyloid stroma revealed specific staining for all three neurohormonal peptides but not for thyroglobulin. The results suggest that differentiated thyroid carcinoma can be regarded as a continuous spectrum of tumor types, with pure follicular carcinomas and classic medullary carcinoma representing the two extremes and the tumors with biphasic features representing a broad intermediate group. The authors suggest that this group be designated "differentiated thyroid carcinoma, intermediate type."

Fat staining in parathyroid disease--diagnostic value and impact on surgical strategy: clinicopathologic analysis of 191 cases.

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Binding of estrogen and progesterone to human endometrium in the different phases of the menstrual cycle. A histochemical study.

Specific estrogen and progesterone binding in human endometrium was studied histochemically using fluorochrome-labeled steroids (estradiol-17 beta-BSA-FITC and progesterone-BSA-TMRITC), endometrial samples from 36 women being investigated. The binding pattern was similar with both reagents. The relationship between the bindings to glands and to stroma, however, varied with the menstrual phase of the tissue. The specific fluorescence was more intense in the epithelial structures in the proliferative phase. In the secretory phase, the fluorescence from stromal cells was as intense as, or more intense than, that from the glands. The localization of the fluorophores in the glandular epithelial cells also varied by menstrual phase. In the proliferative phase, the fluorescence was most intense in the basal part or the whole cytoplasm of the glandular epithelial cells, while in the secretory phase the fluorescence was most intense in the apical and sometimes also in the basal part of the epithelial cells.

Surgical strategy in nonfamilial primary parathyroid hyperplasia: long-term follow-up of thirty-nine cases.

The extent and result of surgery in 39 cases of nonfamilial primary parathyroid hyperplasia followed from 2 to 20 years are reported. Thirteen patients had been subjected to subtotal parathyroidectomy leaving no gland intact, while 26 had undergone less extensive surgery leaving at least one grossly normal or near-normal gland intact without biopsy. In the former group two patients (15%) developed permanent hypoparathyroidism requiring vitamin D treatment. In the latter group there were two patients (8%) with persistent hypercalcemia, which might have been avoided with a subtotal parathyroidectomy. Judging from these results, we believe that an individualized surgical approach is justifiable in nonfamilial primary parathyroid hyperplasia. Subtotal parathyroidectomy, leaving no gland intact, is advocated as the method of choice only when all four glands are enlarged. If one or more glands are grossly normal or near normal, factors such as degree of hypercalcemia, symptoms, age, general condition, and life expectancy should be taken into consideration when the extent of the operation is decided. A more conservative operation leaving at least one grossly normal gland intact without biopsy appears to be sufficient for cure in most of these cases and minimizes the risk for development of permanent hypoparathyroidism.

ABO blood group antigens in parathyroid adenoma and hyperplasia.

Immunohistochemical determination of ABO blood group antigens was performed on parathyroid tissue to see if the presence or absence of such antigens could be used as an aid to distinguish adenoma from hyperplasia in primary hyperparathyroidism. Material from nine cases of solitary adenoma and seven cases of hyperplasia fixed in formalin and embedded in paraffin was studied using monoclonal antibodies and avidin-biotin-peroxidase complex technique. The two categories of tissue did not show any consistent differences in the extent or intensity of immunoreactivity, and the method tested did not permit distinction between adenomatous and hyperplastic disease of the parathyroid glands.

Metabolism of estrone sulfate in endometriotic tissue and in uterine endometrium in proliferative and secretory cycle phase.

The metabolism of [3H]estrone sulfate (E1S) into [3H]estrone (E1) and [3H]estradiol-17 beta (E2) was studied in samples of endometriotic tissue and uterine endometrium obtained simultaneously from 13 patients, 7 in the proliferative and 5 in the secretory cycle phase, and 1 menstruating. E1S was efficiently converted into E1 and E2 by both types of tissue. Total hydrolysis (formation of E1 + E2), as well as the specific formation of E2, was higher in uterine endometrium than in endometriotic tissue, especially in the proliferative phase. Cycle phase associated variations in E2 formation occurred in both tissues, but were statistically significant only for uterine endometrium. E2 formation and total hydrolysis were correlated in endometriotic tissue, but not in uterine endometrium, indicating certain differences in the regulation of estrogen metabolism.

Bilateral and multifocal breast carcinoma. A clinical and autopsy study with special emphasis on carcinoma in situ.

Bilateral clinical breast carcinoma has been reported to appear in up to approximately 10% of patients with breast carcinoma. Increasing diagnostic activity has raised figures of bilaterality, mainly due to detection of lesions of the in situ type. Knowledge of the natural history of carcinoma in situ is incomplete and clinical implications are uncertain. In the present study bilateral lesions were analysed by extensive histological examination in the following groups of patients: (1) Forty-six women (median age 44 years) with clinical and mammographical unilateral invasive breast carcinoma, where the contralateral breast was removed at subcutaneous mastectomy (SCM) during the course of breast reconstruction, 24/46 (52%) had bilateral malignant lesions, four invasive carcinomas and 20 in situ carcinomas (two ductal carcinomas in situ /DCIS/, 15 lobular carcinomas in situ (LCIS), three both DCIS and LCIS). (2) Fifty-two women (median age 50 years) with a unilateral diagnosis of in situ carcinoma (32 DCIS, 16 LCIS, four both DCIS and LCIS), in whom both breasts were removed at SCM. 25/52 (48%) had bilateral malignant lesions, one invasive carcinoma, 24 in situ carcinomas (three DCIS, 18 LCIS, three both DCIS and LCIS). Twelve of 20 cases with LCIS (60%) were bilateral. Of 36 cases with DCIS, seven (19%) were bilateral. (3) The contralateral breast was removed at autopsy in 64 women previously unilaterally mastectomized (at median age 65) for invasive breast carcinoma. Fifteen of 64 (23%) had contralateral primary carcinoma at autopsy, four invasive carcinomas, 11 in situ carcinomas (six DCIS, five LCIS) and 8/64 (13%) had metastases in the breast. Multifocal malignant findings were also analysed in 47 SCM specimens after excisional biopsy for in situ carcinoma. In 35/47 (75%) further malignant lesions were present in spite of normal mammographic and clinical findings. Four were invasive and 31 had in situ lesions (16 DCIS, 10 LCIS, five both DCIS and LCIS): These findings may favour the hypothesis that some carcinomas in situ may remain silent or even regress. It is thus important to embark upon randomized trials to clarify the natural history of breast carcinoma in situ. Such a trial has been started in the southern region of Sweden.

Radiotherapy for unresectable endocrine pancreatic carcinomas.

Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or alpha-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas.

Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.

METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.

Surgical treatment of thyroid carcinoma in a defined population: 1960 to 1977. Evaluation of the results after a conservative surgical approach.

Ninety patients from a demographically well-defined area of, on an average, 243,000 inhabitants were surgically treated for thyroid carcinoma during an 18 year period. Sixty-five of the patients had papillary carcinoma, 20 follicular carcinoma, 4 medullary carcinoma, and 1 anaplastic carcinoma. Seventy-eight patients were operated on for cure, and among them, 23 had total thyroidectomy and 55 partial thyroidectomy. Additional therapy with thyroxine was given to all patients postoperatively. None of the patients treated for cure died from thyroid carcinoma at follow-up 2 to 20 years after diagnosis. One of 42 patients (2.4 percent) primarily treated for cure with lobectomy for papillary carcinoma had local recurrence in the thyroid bed which was excised successfully. No patient treated for cure of follicular carcinoma had local recurrence. All verified recurrences except one were diagnosed within 5 years of primary operation. We conclude that local recurrence after procedures less than total thyroidectomy that are considered to be curative is unusual provided that thyroxine is given postoperatively. Thus it seems that the reported high rates of microscopic carcinoma in the contralateral lobe in patients with unilateral cancer have little clinical significance. A conservative approach in most patients with localized thyroid carcinoma is indicated because it reduces the risk of postoperative complications.

A clinical epidemiologic study of thyroid carcinoma in Malmö, Sweden.

The annual incidence of clinically diagnosed TC in Malmö was, on an average, 2.4 per 100,000 population during the years 1960-1977. This was 1.2 per 100,000 population lower than the corresponding incidence in the whole of Sweden as reported by the National Cancer Registry. The main reason for the difference was suggested to be inclusion in the official figures of autopsy cases and of cases with a benign diagnosis, rather than a true difference in the prevalence of TC. During the later part of the study an increase in the incidence of differentiated TC of approximately 70% was noted. This was considered to be due to increased health awareness and the availability of medical care, because only the number of tumors with less advanced growth increased. The average annual mortality from TC in Malmö was 0.9 per 100,000, which was 0.4 per 100,000 lower than the corresponding official rate in all of Sweden. The difference was suggested to be mainly due to inclusion in the official figures of persons not dying of TC. The mortality did not change significantly during the period of investigation. The percentage distribution by histologic type of tumors clinically diagnosed (N = 104) was as follows: papillary cancer, 65%; follicular, 21%; medullary, 4%; and anaplastic, 12%. The prognosis as estimated by the life table method was worst for patients with anaplastic TC, followed by those with follicular, papillary, and medullary TC. The validity of using the relationship of the tumor to the thyroid capsule (i.e., intrathyroidal and extrathyroidal growth) as a basis for classification into tumor stages was supported in the present study: the mortality in patients with intrathyroidal tumors was lower than in those with extrathyroidal tumors. The definition of occult TC--TC not larger than 1.5 cm, without regard to the relation to the thyroid capsule--was considered inappropriate and a change in the conception of occult TC was proposed. The presence or absence of node metastases in TC did not seem to have major significance for the prognosis. The significance of age for survival was strongly supported in our study. Deaths from TC clinically diagnosed before the age of 60 were infrequent, whereas the disease after this age increasingly often was fatal. This was partly due to a late onset of anaplastic TC and partly to a higher mortality in older than in younger patients with papillary or follicular TC.(ABSTRACT TRUNCATED AT 400 WORDS)

Percutaneous injection of contrast medium into breast lesions for radiographic exclusion of malignancy.

Contrast medium was injected percutaneously into palpable breast lesions in 63 patients in order to demonstrate lactiferous ducts. Of 35 benign and mammographically definable tumours, 30 were successfully punctured and ducts were visualized in 20, while ducts were demonstrated in seven of 21 non-definable lesions. Ducts were seen in 10 of 13 fibroadenomas removed by surgery, in two of four hamartomas, and in two of three cases of mastitis. No ducts were seen in six solid, malignant tumours examined, while one intracystic papillary carcinoma showed filling defects caused by the malignant growth. It was concluded that the method is simple, and that the demonstration of ducts is an indication of the benign nature of a lesion.

Histogenesis of thyroid carcinoma.

Follicular and papillary thyroid carcinoma have for many years been regarded as biologically distinct from medullary thyroid carcinoma. The recent recognition of a tumor type which is morphologically and functionally intermediate between these two categories suggests however that differentiated thyroid carcinoma may be regarded as a continuous spectrum of tumor types all of which are derived from a common thyroid stem cell, capable of developing both follicular and parafollicular tumor cells, as well as intermediate cell forms. It is also proposed that anaplastic giant cell thyroid carcinoma represents a heterogeneous group consisting of the anaplastic counterparts not only to follicular and papillary carcinoma but also to the intermediate type and to classical medullary carcinoma.

Detection of humoral antibodies to Renibacterium salmoninarum in rainbow trout Oncorhynchus mykiss and Atlantic salmon Salmo salar challenged by immersion and in naturally infected populations.

Humoral antibodies to heat-stable antigens of Renibacterium salmoninarum (Rs) were detected by enzyme-linked immunosorbent assay (ELISA) in rainbow trout Oncorhynchus mykiss and in Atlantic salmon Salmo salar challenged by immersion. A slow antibody response was found: 3% (1/30) was positive 4 wk after immersion and 72% (26/36) was positive after 8 wk. All 30 fish sampled after 4 wk were found to be infected, as determined by bacterial culture and/or the presence of soluble antigens in the kidney. At 6, 8 and 12 wk after immersion the proportion of positives indicated by ELISA was 58%. The Rs infection was detected by cultivation in 36% of sampled fish collected on the same occasion. Elevated antibody titres to Rs were detected in samples from both Atlantic salmon (59% in 1 farm) and from rainbow trout (20% in 1 of 5 sampled farms) in naturally exposed populations all of which classified positive for bacterial kidney disease (BKD). Elevated antibody titres were detected among sampled fish from populations of rainbow trout and salmon with clinical BKD. Samples collected from farm populations of rainbow trout, salmon and brown trout Salmo trutta, exposed to Rs but without clinical BKD, were negative in the ELISA, although Rs bacteria or soluble antigens were detected at the same sampling. The antibody ELISA method cannot be recommended for general fish health monitoring purposes, but may be a valuable tool for monitoring the disease progression during controlled experiments.