Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases.

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Cardiac neoplasms at the Canadian Reference Centre for Cancer Pathology.

OBJECTIVE: To review the Canadian Reference Centre for Cancer Pathology's experience with cardiac neoplasms by reviewing all cases with tumours involving the heart referred to the Centre from 1949 to 1995. Referred patient records, panel and consensus statement submissions and glass slides were reviewed in all cases. In selected cases additional immunohistochemical stains were obtained from paraffin block tissues. SETTING: National referral centre for difficult or interesting cancer pathology-related cases. PATIENTS: All cases were derived from referral of autopsy material and/or surgically resected neoplasms. Material was referred from 35 patients during 1949 to 1995. The group consisted of 17 males, 17 females and one infant patient in whom the sex was not specified. The patient age ranged from infancy to 85 years. RESULTS: The neoplasms referred consisted of 12 myxomas, 10 sarcomas, five lymphomas, two carcinomas, two papillary fibroelastomas and one each of rhabdomyoma, mesothelioma of the atrioventricular node, lipomatous hypertrophy of the intra-atrial septum and fibroma. The sarcomas were difficult to classify even with the use of additional immunohistochemical stains. All the lymphomas were of non-Hodgkin's type and were not of primary cardiac origin. CONCLUSIONS: The series of neoplasms referred to the Canadian Reference Centre for Cancer Pathology reflects changes in cardiac surgery, cardiac imaging and cardiac pathology as disciplines. Even with modern pathological techniques some cases, especially sarcomas, are still difficult to diagnose. The clinical presentation often reflects the chamber of origin of the neoplasm rather than being indicative of a specific tumour type.

Immunohistochemical study of papillary thyroid carcinoma and possible papillary thyroid carcinoma-related benign thyroid nodules.

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.

A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor.

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Infiltrating papillary thyroid carcinoma: review of 134 cases of papillary carcinoma.

BACKGROUND: Papillary thyroid carcinomas (PTCs) are diagnosed mainly by the features of nuclei of the neoplastic cells. Theoretically, by similarity to other types of carcinoma, infiltrative tumor growth likely distinguishes the thyroid neoplastic lesions with potential of metastasis from those without this capability. METHODS: One hundred thirty-four cases of PTC, consisting of 41 encapsulated tumors and 93 nonencapsulated tumors, were examined for the presence of infiltrating PTC (IPTC), defined by tumor cells infiltrating a desmoplastic or sclerotic stroma. RESULTS: Encapsulated tumors with focal or extensive IPTC and nonencapsulated tumors with focal or extensive IPTC were associated with rates of lymph node metastases of 28%, 42%, 36%, and 65%, respectively. The tall cell variant of PTC was associated with a higher rate of metastasis. There was a small group of tumors without identifiable IPTC, designated as PTC without identifiable infiltrating carcinoma, which included six encapsulated tumors with areas of sclerosis in the capsule and three nonencapsulated tumors consisting of neoplastic cells with optically clear nuclei, nuclear grooves, and intranuclear inclusions in over two thirds of the cell population. Of these lesions, one case developed lymph node metastases. Papillary thyroid tumors without areas of IPTC and exhibiting the nuclear changes described, but in less than two thirds of the tumor cells, did not develop lymph node metastases. CONCLUSIONS: Infiltrating tumor growth is an indicator of malignant behavior in most thyroid papillary neoplastic lesions. The extent of IPTC is likely proportional to the rate of lymph node metastases.

Papillary thyroid carcinoma and related thyroid neoplastic lesions: a light microscopic study with emphasis on nuclear changes.

A total of 187 thyroid lesions consisting of 2 cases of Grave's disease, 21 cases of multinodular goiter, 40 follicular adenomas and 124 low-grade papillary thyroid carcinomas were studied to identify intermediate neoplastic lesions in the spectrum of nuclear changes between benign reactive thyroid follicles and low-grade thyroid papillary carcinoma. The lesions were examined and classified on the basis of the following nuclear features: fine chromatin seen in the thyroid papillary carcinomas and coarse chromatin seen in follicular carcinomas. Cases with Hürthle cell changes were excluded from the study. Cases with nuclei containing coarse chromatin were classified in the group of follicular adenomas with a coarse chromatin pattern. The neoplastic thyroid lesions containing fine chromatin showed a spectrum of nuclear changes ranging between reactive follicular lesions and papillary thyroid carcinoma with lymph node metastasis. Such lesions were classified as follicular adenomas with a fine chromatin pattern. The nuclei of these lesions were graded into mild to marked "nuclear atypia with a fine chromatin pattern". The degree of atypia depended on the degree and extent of nuclear changes. Encapsulated follicular adenomas with a fine chromatin pattern and with mild atypia (11 cases), moderate atypia (13 cases), marked atypia (27 cases), and encapsulated or nonencapsulated papillary thyroid carcinoma were characterized by uniform nuclei; with mild, moderate and marked nuclear atypia in less than 2/3 of the cell population and marked nuclear atypia in more than 2/3 of the cell population; and measuring 5.4-6.3, 6.0-7.2, 6.3-9 and 7.2-10 microns in diameter, respectively. Follow-up of cases of papillary thyroid carcinoma fulfilling the above criteria showed lymph node metastasis in 33% of cases, whereas follicular adenomas with a fine chromatin pattern, including cases originally diagnosed as papillary carcinoma, showed no evidence of lymph node or distant metastasis in a follow-up period of 30 months to 15 years. In the thyroid tissue surrounding papillary thyroid carcinoma or encapsulated follicular adenoma with a fine chromatin pattern and marked atypia, adenomatous nodules with a fine chromatin pattern and with low-grade nuclear atypia were identified. The adenomatous nodules with a fine chromatin pattern and with mild, moderate and marked atypia showed architectural, cytoplasmic and nuclear features similar to those of follicular adenoma with a fine chromatin pattern of the same grade. Of interest, a large number of cases of follicular adenoma with a fine chromatin pattern had areas with features of follicular adenoma with a coarse chromatin pattern.

Fine-needle aspiration biopsy of chondroblastic osteosarcoma of the vertebral column complicated by Corynebacterium infection: a case report.

We describe a case of chondroblastic osteosarcoma of the vertebral column in a 67-yr-old male in whom the preoperative diagnosis was made by fine-needle aspiration biopsy (FNAB). This diagnosis was subsequently confirmed in the T8 corpectomy specimen. Although the smears of the aspirate revealed only occasional markedly atypical spindle-shaped nuclei, the cell block was diagnostic of malignancy. It showed a well-preserved fragment of neoplastic cartilage populated by markedly atypical hyperchromatic cells and a crushed fragment of anaplastic spindle-shaped cells surrounded by opaque collagenous matrix reminiscent of osteoid. The surgically resected specimen exhibited comparable histological features as well as colonies of gram-positive bacilli within the necrotic tumor. Culture confirmed the presence of Corynebacterium species. It is likely that these skin organisms were introduced at the time of FNAB. This case demonstrates the value of FNAB in the diagnosis of primary bone tumors and reports a rare complication of this procedure.

Neoplastic non-papillary thyroid carcinoma lesions with a fine chromatin pattern.

In papillary thyroid carcinoma (PTC) in cytological and surgical specimens, fine chromatin, nuclear grooves and nuclear pseudoinclusions are the hallmarks of diagnosis. We investigated the significance of these nuclear changes in neoplastic non-PTC lesions. Fine needle aspiration biopsies (FNAB) of thyroid lesions were reviewed with histologic correlation. Twenty-five low-grade PTC and 35 neoplastic non-PTC lesions with a fine chromatin pattern in cytology specimens were identified. These lesions were studied along with five multinodular goiters and five follicular adenomas with a coarse chromatin pattern. The neoplastic non-PTC lesions were selected from cases with a histopathologic diagnosis of follicular neoplasm (accompanied by cytopathologic examination) but lacking a coarse chromatin pattern. The nuclear changes were separated into three grades of nuclear atypia with a fine chromatin pattern, depending on the degree of nuclear enlargement and nuclear membrane thickening, or the presence of nuclear grooves or pseudoinclusions. Thyroid lesions with a higher grade of nuclear atypia with a fine chromatin pattern were associated with larger nuclei and more readily visible nucleoli. These lesions correlated histologically with PTC and follicular adenomas with a fine chromatin pattern. The latter could be divided into three grades: grade 1 lesions having a fine chromatin pattern similar to that of nuclei with open chromatin seen in areas of nodular goiter; grade 3 lesions having nuclear features closest to those of PTC; and grade 2 lesions showing intermediate changes. In conclusion, there is a spectrum of nuclear changes in neoplastic non-PTC lesions with a fine chromatin pattern. These lesions are often diagnosed as follicular adenomas in surgical pathology and pose cytopathologic diagnostic problems between nodular goiter, follicular adenoma and PTC. The significance of follicular adenomas with a fine chromatin pattern will be discussed.

Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hürthle cell and/or apocrine-like changes.

BACKGROUND: We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. METHODS AND RESULTS: Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes. CONCLUSIONS: All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma.

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.