Microfollicular Pattern Research Articles

High-Resolution Sonographic Findings of Ovarian Granulosa Cell Tumors

This study was performed to determine the high-resolution sonographic findings of ovarian granulosa cell tumors (GCTs) and to correlate the sonographic findings with the pathologic findings. A retrospective review of sonographic findings was conducted on 16 patients with surgically proven ovarian GCTs. Patients' ages ranged from 10 to 64 years (mean, 37.7 years). We evaluated the sizes and morphologic appearances of the ovarian tumors. The blood flow patterns of the tumors were assessed with Doppler sonography (n = 6). Sonographic findings were compared with pathologic findings. The maximal diameters of the masses were 2.0 to 15.4 cm (mean, 8.2 cm). The morphologic appearances of the masses were classified into 3 patterns; solid and cystic (n = 10), solid with a sponge form appearance (n = 4), and entirely solid (n = 2). The measured resistive index and pulsatility index of the solid portions were 0.23 to 0.5 and 0.26 to 0.62, respectively. Pathologic diagnoses of 13 adult ovarian GCTs and 3 juvenile GCTs were obtained. The solid and cystic masses had GCTs with macrofollicular and microfollicular patterns pathologically. The solid masses with a sponge form appearance had prominent hemorrhagic necrosis and diffuse proliferation of granulosa cells with trabecular and microfollicular patterns. The entirely solid masses had diffuse cellular proliferation with a trabecular pattern without cystic changes or hemorrhagic foci. Sonographic findings of ovarian GCTs included solid and cystic masses, solid masses with a sponge form appearance, and entirely solid masses, and the sonographic findings correlated well with the histopathologic findings.

A cell pattern approach to interpretation of fine needle aspiration cytology of thyroid lesions: A cyto-histomorphological study

Aim:Our study aimed at a cell pattern approach to interpret thyroid cytology and to demonstrate diagnostic accuracy of fine needle aspiration cytology (FNAC) with an emphasis on diagnostic pitfalls.Materials and Methods:A total number of 218 goitre cases, from the year 2000 to 2004, were reviewed retrospectively from the cytology files, without considering the previous cytological diagnosis. Four cases with inadequate aspirate were excluded. The predominant cell pattern, such as macro/normofollicular, microfollicular, papillary, syncytial, dispersed and cystic pattern, was noted in each case. The final diagnosis was arrived by observing the cellular details and background elements. Cytological diagnosis was correlated with histopathology in 75 cases. The sensitivity and specificity were computed.Results:Normo/macrofollicular pattern was seen in 71.96% of nodular goitre and 6.9% of follicular neoplasms. Around 86.2% of follicular neoplasms and 17.6% of papillary carcinoma had microfollicular pattern. The papillary pattern was seen in 47% of papillary carcinoma. Syncytial pattern was noticed in 72.3% of chronic lymphocytic thyroiditis and 29.4% of papillary carcinoma. Cytological diagnosis was concordant with histopathological diagnosis in 65 cases. Overall sensitivity and specificity of FNAC in diagnosing neoplastic lesions of thyroid were 83.33 and 95.55%, respectively.Conclusion:FNAC is more sensitive and specific in triaging neoplastic from non-neoplastic thyroid lesions. Identification of the predominant cell pattern would be complementary to analysis of cell morphology and background details in cytological diagnosis of thyroid lesions. This approach helps to diagnose follicular neoplasm and follicular variant of papillary thyroid carcinoma.

Biphasic Malignant Testicular Sex Cord-Stromal Tumor in a Cotton-top Tamarin (Saguinus oedipus) with Review of the Literature

A 20-year old male cotton-top tamarin (Saguinus oedipus) was presented with unilateral enlargement of an intrascrotal testicle. Fine-needle aspiration cytology demonstrated a neoplastic population with Call-Exner-like bodies and features of malignancy. The animal was castrated, and histologic examination revealed a biphasic sex cord-stromal tumor, with one region resembling Sertoli-cell tumor and one region resembling granulosa-cell tumor, with extensive microfollicular pattern and many Call-Exner bodies. Eight months after castration, the animal was euthanized on discovery of a caudal abdominal mass that displaced organs, was highly infiltrative, and extended into the paravertebral musculature with lysis of vertebral bone. Metastases to lymph node and lung were also present. Histologic examination of the abdominal tumor showed multifocal formation of Call-Exner bodies in an otherwise highly dedifferentiated population. Positive immunolabeling for alpha inhibin confirmed the sex cord-stromal origin of the abdominal and paravertebral tumor masses. This case has similarities to malignant testicular granulosa-cell tumor of humans.

Parathyroid tissue in an adult’s cervical bronchogenic cyst

Dear Editor, Bronchogenic cysts are rare, benign, congenital lesions that occur due to aberrant tracheobronchial tree development during embryogenesis [1–3]. They usually present in childhood, in the lungs or mediastinum, while cervical cysts are infrequent [1, 2]. Neither parathyroid gland absorption by a bronchogenic cyst nor parathyroid tissue in such a lesion has been reported. An adult’s cervical bronchogenic cyst containing parathyroid tissue, incidentally found during thyroidectomy in the right superior parathyroid gland location, is presented. A 52-year-old man presented with a multinodular goitre. Thyroid function, parathormone and calcium were normal. Ultrasound demonstrated a multinodular goitre with a 3-cm dominant nodule in the left and a 4-cm dominant nodule in the right thyroid lobe; no lymphadenopathy or additional abnormal findings were identified. Fine-needle aspiration cytology of both nodules revealed follicular cells with microfollicular pattern, occasionally showing oncocytic changes and nuclear pleomorphism but no malignant changes (Thy3 according to the Classification of the Royal College of Physicians [4]). Intraoperatively, a big multinodular goitre and a cyst in the right superior parathyroid gland location, interpreted as parathyroid cyst, were identified. No lymphadenopathy was observed. Total thyroidectomy and cyst excision were performed. The other three parathyroid glands were preserved. The thyroid gland (10×8×3 cm, 87.5 g) consisted of an enlarged (8×5.5×3 cm) multinodular right and an enlarged (4.5×3×3.5 cm) nodular left lobe. The latter lobe was almost entirely replaced by a well-circumscribed, encapsulated nodule (3.5×2.4×3 cm), which consisted of follicles with microfollicular and solid architecture and, focally, Hurthle cell changes. A focus of capsular and few foci of vascular invasion were noted. No papillary pathology features were found. Ki-67 proliferative index was <1%. Minimally invasive follicular thyroid carcinoma with capsular and vascular invasion diagnosis was offered. The cyst (0.8×0.4×0.3 cm, 0.16 g) was thin-walled, unilocular. Microscopically, the inner surface was lined by ciliated, pseudostratified, cuboidal to columnar epithelium with goblet cells. The cystic wall contained smooth muscle, seromucous glands and islands of parathyroid tissue (Fig. 1). This was confirmed by immunohistochemical parathormone demonstration (Fig. 2). There was no evidence of malignancy. A diagnosis of benign bronchogenic cyst with parathyroid tissue in its wall was made. Cervical bronchogenic cysts are infrequent, usually diagnosed in children but can rarely be encountered in adults; such aberrant location could be explicable by migration of abnormal tracheobronchial tree buds during embryogenesis [1–3]. They are often asymptomatic, frequently found incidentally during radiologic evaluation or, seldom, thyroidectomy as in our patient [5]. Although rare, they should be included in the differential diagnosis of cervical masses. Characteristic histologic findings are a ciliated, respiratory-type, pseudostratified epithelial lining with smooth muscle cells, mucous glands, cartilage and fibrous connecVirchows Arch (2008) 453:307–308 DOI 10.1007/s00428-008-0655-0

Absence of microfollicular basement membrane: A new indicator in the diagnosis of follicular carcinoma thyroid

The thyroid follicles represent a biological continuum. Each follicle is closely related to the follicle that is next to it. The important feature of a follicular carcinoma is a microfollicular pattern. We report a case of follicular carcinoma in a 48-year-old female that demonstrates microfollicles which are larger in size and contain more number of follicular cells in cytologic smears (20-29 cells) in contrary to the literature definition of microfollicles containing approximately 6-12 cells. We also demonstrate absence of basement membranes in these microfollicles in histologic sections by Silver Methanamine Stain, which may be an indicator to search for vascular and capsular invasion. This case report also describes postoperative positron emission tomography scan findings.

The spectrum of histologic changes in thyroid hyperplasia: a clinicopathologic study of 300 cases

Thyroid hyperplasia is a physiologic response of follicular epithelium to hormonal changes that result in disturbances in the feedback mechanism of thyrotropin-releasing hormone and thyroid-stimulating hormone. The most common manifestation of this process is the so-called sporadic goiter (diffuse or nodular hyperplasia), a condition that may be associated with a variety of stimuli. Some of the histologic changes that can be observed in hyperplasia of the thyroid can sometimes lead to an incorrect diagnosis of malignancy. We studied 300 consecutive cases of hyperplasia of the thyroid to evaluate morphologic features that could potentially be mistaken for neoplastic conditions. Florid papillary hyperplasia of follicular epithelium was observed in 13% of cases, in several instances closely resembling the papillary structures of papillary thyroid carcinoma. Foci displaying nuclear clearing closely resembling "Orphan-Annie" nuclei were present in 15% of cases. Nuclear grooves and pseudonuclear inclusions were also identified focally in 8% of cases. Cytologic atypia was observed in 7% of cases, including nuclear enlargement, multinucleation, and nuclear pleomorphism with prominent nucleoli. Mitoses were observed in 6% of cases and averaged 1 to 2 per 20 high-power fields. This finding was usually seen in the more cellular areas in cases characterized by a solid, microfollicular pattern of growth. Psammoma bodies were observed focally in 4 cases (1.3%). Infiltration of adjacent skeletal muscle by benign hyperplastic follicles was seen in 3 cases (1%). Another unexpected finding in 2 cases was the identification of small clusters of normal thyroid follicles within the sinuses of lymph nodes located adjacent to the gland (>1%). The present study confirms that thyroid hyperplasia can sometimes display features that may be confused for a malignant neoplastic process. Awareness of such features and their recognition are of importance to avoid a misdiagnosis of malignancy.

Cutaneous metastasis from follicular variant of papillary thyroid carcinoma: A case diagnosed on cytology

A 40-year-old woman presented with a scalp swelling. A careful clinical examination revealed a left-sided deep-seated thyroid nodule. Fine needle aspiration from both sites disclosed a microfollicular architectural pattern on Giemsa stain and pale nuclei with nuclear grooves on Papanicolaou stain, indicating the possibility of follicular variant of papillary thyroid carcinoma with metastasis to the scalp. Histologic tissue evaluation confirmed the diagnosis. Thus, a diligent search for nuclear features should be performed to enable a diagnosis of follicular variant of papillary thyroid carcinoma on cytology. This helps in patient management obviating the need for a second surgical intervention.

Follicular thyroid carcinoma with metastasis to skin diagnosed by fine needle aspiration cytology

In April 2006, a 55-year-old female presented with a thyroid mass and multiple skin nodules on scalp, forehead and neck. Fine needle aspiration cytology of thyroid mass and multiple skin nodules show tumor cells clusters in a repetitive microfollicular pattern on May-Grunwald-Giemsa stain suggestive of follicular thyroid carcinoma with metastasis to skin. Although follicular carcinoma have a propensity for vascular invasion and hematogenous dissemination, skin is not commonly involved. Only a few cases of cutaneous metastasis from follicular thyroid carcinoma are reported in the English language literature.

Follicular Variant Papillary Thyroid Carcinoma Arising within an Ovarian Teratoma

A 49-year-old female presented to the hospital with abdominal pain and emesis. A computed tomography (CT) scan revealed a small-bowel obstruction and a right ovarian mass measuring 4.6 cm. Following oophorectomy, histopathology revealed a mature cystic teratoma with multiple foci of benign thyroid tissue, as well as a 0.9 cm focus of follicular variant papillary thyroid cancer (Figs. 1 and ​and2)2) surrounded by normal ovarian tissue (Fig. 3). Thyroid ultrasound and serum thyroid function tests were normal. A 131I diagnostic whole body scan (WBS) did not reveal any abnormal uptake in the abdomen or pelvis, and an abdominal CT was normal. A high-dose (423 i Ci) 123I WBS performed 6 months later was also negative. Based on the small size of the primary carcinoma and the lack of evidence of metastases on imaging, the patient received no further treatment. FIG. 1 Follicular variant papillary thyroid carcinoma within an ovarian teratoma. Normal ovarian tissue is seen on the left (N). On the right, normal-appearing thyroid tissue (T) merges with a focus of follicular variant papillary thyroid carcinoma (PTC). FIG. 2 High-power magnification of follicular variant papillary thyroid carcinoma arising within ovarian teratoma. The tumor has predominantly microfollicular growth pattern with occasional normal-sized follicles filled with colloid (C) and lined by cells with ... FIG. 3 Normal ovarian tissue from the same ovary. Note the presence of normal ovarian stromal cells and blood vessels. Differentiated thyroid cancer (DTC) arising from ovarian teratomas is a rare occurrence, with an estimated incidence of 0.1–0.3% (1,2). Most cancers are found incidentally on histopathology. DTCs arising from ovarian teratomas can occasionally present with locally invasive disease or with distant metastases, and may be associated with recurrences in some patients (2). Following surgical resection of the lesion, the need for further therapy, including total thyroid-ectomy and radioiodine ablation, is based on the extent of the primary lesion and the evidence of persistent or meta-static disease by imaging. There is very little data on the natural history or prognosis of papillary microcarcinomas of ovarian origin. Given the similarity of their histological appearance to those arising in the thyroid, a generally favorable prognosis is anticipated.

Gonadoblastoma: evidence for a stepwise progression to dysgerminoma in a dysgenetic ovary

Gonadoblastomas are neoplasms of dysgenetic gonads which may undergo regression or become overgrown by malignant germ cell tumors (mGCTs). Since little is known about their relationship to normal gonadal development and mGCTs, we studied the phenotype and antigenic profile of gonadoblastomas in comparison with adjacent dysgerminomas and fetal gonads. Three cases of gonadoblastomas and fetal gonads of both sexes were analyzed using oncofetal markers to M2A-antigen (M2A), germ cell alkaline phosphatase (PLAP/GCAP), receptor tyrosine kinase c-kit (c-kit), and somatic angiotensin converting enzyme (sACE) as well as the proliferation marker MIB-1. Morphologically, microfollicular pattern of gonadoblastomas showed a fetal germ cell organization reminiscent of oocytic clusters of fetal ovaries. They contained both cell types, similar to oocytes (M2A-, GCAP-, c-kit+/-, sACE-) and oogonia (M2A+, GCAP+, c-kit+, sACE+). The percentage of germ cells immunoreactive for oncofetal markers and the proliferation index increased from microfollicular over coronary patterns to adjacent dysgerminomas. Supportive cells of gonadoblastomas showed a uniform phenotype (CK18+, vimentin+, sACE+, alpha-inhibin+, M2A-) but in contrast to fetal germ cells lacked a clear equivalence to fetal tissues. Our results show that gonadoblastomas mimic female fetal ovary and exhibit a stepwise progression from follicular pattern to coronary pattern and finally to dysgerminomas.

Thyroid Cytology and Risk of Thyroid Cancer: Differences Among Indeterminate Specimens

To assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies. We attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available. Of the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%). The results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer.

Core I gene is overexpressed in Hürthle and non-Hürthle cell microfollicular adenomas and follicular carcinomas of the thyroid

BackgroundMost of the steps involved in the initiation and progression of Hürthle (oncocytic, oxyphilic) cell carcinomas of the thyroid remain unknown.MethodsUsing differential display and semiquantitative RT-PCR we found, among other alterations, overexpression of the gene encoding the Core I subunit of the complex III of the mitochondrial respiratory chain in a follicular carcinoma composed of Hürthle cells.ResultsSimilar high levels of Core I gene expression were detected in nine follicular carcinomas (seven with Hürthle cell features), in seven microfollicular adenomas (one with Hürthle cell features) and in one micro/macrofollicular adenoma, in contrast to a lower/normal expression in nine papillary carcinomas (three with Hürthle cell features) and five macrofollicular adenomas (one of which displaying Hürthle cell features). No significative correlation was found between Core I overexpression and the proliferative activity of the lesions.ConclusionsWe conclude that Core I overexpression in thyroid tumours is not associated with malignancy, Hürthle cells or proliferative activity. The pathogenetic mechanism linking Core I overexpression to the microfollicular pattern of growth of thyroid tumours remains to be clarified.

Thyroid cytology and the risk of malignancy in thyroid nodules: importance of nuclear atypia in indeterminate specimens.

Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid nodules. However, cytologic interpretation of FNA specimens is often difficult, especially in the presence of indeterminate microfollicular cytologic patterns, which are thought to suggest follicular neoplasm (adenoma or carcinoma). To assess the risk of malignancy associated with specific cytologic patterns, we correlated preoperative FNA cytologic patterns (n = 484 reports including repeat aspirations) with final histological diagnoses for 368 surgical thyroid specimens obtained during the period 1994-1998. The overall prevalence of malignancy in the surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%). Nodules with indeterminate cytologic patterns in the absence of nuclear atypia (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia consistent with follicular neoplasm were malignant (60%), including specimens with or without microfollicular cytology. Nodules with frankly malignant cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses of papillary carcinoma were confirmed at surgery in all 49 cases. These results indicate that indeterminate microfollicular cytologic patterns in the absence of nuclear atypia are associated with a low risk of malignancy, at least in this series. This finding suggests that many nodules with such microfollicular cytology might be managed conservatively with observation. In contrast, cytologic nuclear atypia consistent with a follicular neoplasm confers a high risk of cancer. In addition, frankly malignant cytologic diagnoses, especially papillary carcinoma, are highly reliable, and thus may be used as a guide for planning surgery appropriate for thyroid cancer.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Distribution of sialic acid-dependent carbohydrate epitope in thyroid tumors: immunoreactivity of FB21 in paraffin-embedded tissue sections.

The reactivity of monoclonal antibody FB21, which recognizes a sialic acid-dependent carbohydrate epitope, was tested with 94 non-neoplastic and neoplastic thyroid tissue specimens using immunohistochemical methods on formalin-fixed, paraffin-embedded tissue sections. These specimens included 11 cases of adenomatous goiter, three cases of Basedow's disease, 30 cases of follicular adenoma, 20 cases of papillary carcinoma, 15 cases of follicular carcinoma, six cases of medullary carcinoma, and nine cases of anaplastic carcinoma. FB21 reacted with 14 of 15 cases of follicular carcinoma that showed a microfollicular or trabecular pattern, and with nine of 20 cases of papillary carcinoma. A positive reaction was found on the cell surface membranes or apical parts of neoplastic follicles. FB21 also reacted with five of 30 cases of follicular adenoma. These cases showed a follicular pattern and positive staining pattern similar to that in follicular carcinoma. Adenomatous goiters, Basedow's disease, medullary carcinomas, and anaplastic carcinomas were negative for FB21 reactivity. Although the different reactivities of FB21 with papillary carcinoma and follicular carcinoma remain to be investigated, the high frequency of reactivity with FB21 suggests that it may be useful as a complement to morphological diagnosis in follicular carcinoma.

Dyshormonogenetic goiter: A clinicopathologic study of 56 cases

Dyshormonogenetic goiters (DG) are genetically determined thyroid hyperplasias due to enzyme defects in thyroid-hormone synthesis. We report 56 cases of DG occurring in 34 females and 22 males. The patients age ranged from newborn to 52 yr (median 16), 75% of the cases occurring before the age of 24. All patients presented with clinically evidence of goiter except for two patients that were diagnosed at autopsy. Hypothyroidism was documented before the histological diagnosis was made in 36 patients (64%). The thyroid gland was enlarged and multinodular in all cases, weighing up to 600g. Microscopically, the most common alteration consisted of markedly cellular nodules exhibiting a variety of architectural appearances, the solid and/or microfollicular patterns predominating. Papillary proliferations and an insular growth pattern were also present. Fibrosis was a common finding; in some instances it was very conspicuous, resulting in irregularities at the edge of the nodules simulating capsular invasion. Other constant features included marked nuclear atypia and minimal amount of colloid. In 18% of the cases, the degree of hyperplasia and atypia were such as to result in a mistaken diagnosis of follicular, papillary, medullary, or undifferentiated carcinoma. Three of the glands contained incidental small neoplasms fulfilling the criteria of papillary microcarcinoma; one of them was multicentric. The presence in a thyroid gland of the combination of these morphologic features should suggest the diagnosis of dyshormonogenetic goiter. The only other condition we are aware of that can result in a similar microscopic picture is iatrogenic goiter resulting from the administration of antithyroidal agents.

Clinical, Pathological, and Molecular Studies of Two Families with Iodide Organification Defect.

Two unrelated families (CA and NA) in which an iodide organification defect (lOD) was present in two siblings of each family were studied. These patients had congenital goiters with hypothyroidism and a positive perchlorate discharge test. Examination of the thyroid tissue revealed no thyroid peroxidase (TPO) activity. Histologic findings were consistent with a microfollicular pattern of hyperplasia. Moderate cellular atypia was present, characterized by nuclear pleomorphism and hyperchromatism. Full length thyroglobulin was purified by gel filtration, but was not iodinated. Immunohistochemical studies using a polyclonal anti-human thyroid peroxidase (hTPO) antibody confirmed the presence of immunoreactive TPO protein in the thyroid tissues. Samples of normal and affected individuals were studied with respect to the presence of various fragments using TPO probes of varying sizes. The two affected siblings from family CA were homozygous for fragments 3.9, 4.6, and 7.0 kb (8g111) and 2.3 and 2.9 kb (Ta ql), whereas the parents were heterozygous. In the other family (NA), the Bg/ll digestion and TPO-31 hybridization revealed an interesting and informative polymorphism. The parents showed two different polymorphic patterns: the father had a 5.0/4.6 kb pattern and the mother a 4.7/4.5 kb pattern. However, the two affected siblings showed the same heterozygotic allelic pattern at 4.5/4.6 kb. The restriction fragment length polymorphism detected in these two families suggests an association between the TPO gene and an lOD. Results suggest that in these dyshormonogenetic tissues an altered TPO protein molecule is being synthesized, without detectable in vitro activity, but visible by immunostaining techniques in the goitrous tissue. Mutations in the TPC gene sequence are most likely associated with these changes.

Sex cord-stromal tumors of the ovary

The developmental relationship between granulosa and stromal cells in the fetal ovary was reviewed. The proliferation and expression of basic fibroblast growth factor (bFGF) and luteinizing hormone receptor (LHR) of both the granulosa and theca cells was examined in the adult ovary. Ovarian granulosa cell tumors were then studied under light and electron microscopy and for immunohistochemical expression of bFGF and LHR. In the follicular development of the adult ovary, bFGF expression in the granulosa cells was correlated with theca cell proliferation. In ovarian granulosa cell tumors, estrogen-producing tumors showed a stratified or microfollicular pattern being accompanied by theca cells which had ultrastructural features of steroid-production, and these tumor cells exhibited immunoreactivity for bFGF. In contrast, tumors with no apparent hormone-production showed a solid or gyriform pattern without admixture of theca cells, and were negative for bFGF. LHR was expressed in both types of tumor. Accordingly, bFGF may play an important role in association with the theca cell component in granulosa cell tumors.

Dyshormonogenetic goiter: A morphological and immunohistochemical study.

A retrospective morphological and immunohistochemical study of 21 cases of dyshormonogenetic goiter was carried out correlating patterns of hyperplasia and the atypias of the glandular tissues with specific defects in hormonal synthesis, including (1) thyroglobulin synthesis defect (Group I, n = 8); (2) defective organification of iodide (Group II, n = 11); and (3) iodide transport defect (Group III, n = 2). Microfollicular, trabecular, papillary, and oxyphilic cell patterns were more frequent in Group II compared with Group I (Group III was excluded because of the small number of cases). The combined microfollicular and trabecular patterns were more frequently seen in patients in Group II. Two cases of thyroglobulin synthesis defect demonstrated certain morphological specificity characterized by an alveolar pattern. Atypias were more frequent and severe in patients in Group II relative to patients in Group I, but features of malignancy were not found in any patients. Immunohistochemical study using thyroglobulin antiserum demonstrated correlation between morphology and positivity of follicular cells. Scarce C cells were verified in these cases by immunohistochemistry. Using two-paired samples, respectively, of 21 endemic and 21 dyshormonogenetic goiters, we distinguished 85.7% of the cases examined, presented in a double-blind fashion. Scarcity of colloid and prominent cellular atypia were highly suggestive of dyshormonogenetic goiter. Considering the relative rarity of dyshormonogenetic goiter, our studies point out the most common patterns of hyperplasia and atypias in this pathology to avoid misdiagnosis, principally when considering the possibility of malignancy.

Ovarian granulosa cell proliferations of pregnancy: A report of nine cases

Granulosa cell proliferations that simulated small neoplasms were incidental findings in the ovaries of nine pregnant women. The lesions were typically multiple and associated with atretic follicles. In eight cases, the granulosa cells were arranged in solid, insular, microfollicular, and trabecular patterns, but in the ninth case, there was a prominent sertoliform tubular pattern. The granulosa cells typically contained scanty cytoplasm and grooved nuclei, resembling the cells of adult-type granulosa cell tumors. However, in one case large nodules of markedly luteinized cells with variably sized, round, nongrooved nuclei were present; the nodules in this case superficially resembled pregnancy luteomas. In the case with a sertoliform pattern, the cells had abundant vacuolated cytoplasm. The lesions described probably reflect an unusual physiological response to the elevated chorionic gonadotropin level of pregnancy rather than early stages of neoplasia.