Fine-needle aspiration cytology of papillary Hürthle cell carcinoma with lymphocytic stroma “Warthin-like tumor” of the thyroid

Papillary Hürthle cell carcinoma with lymphocytic stroma is a recent addition to the list of variants of papillary carcinoma of the thyroid. We report the aspiration cytology and histology findings of this tumor arising in two patients. The smears were cellular, and revealed Hürthle cells arranged in three-dimensional groups, papillary fragments, and as singly dispersed cells with a prominent intimately associated inflammatory component of lymphocytes and few plasma cells. The Hürthle cells were pleomorphic and showed granular eosinophilic cytoplasm, eccentrically oriented nuclei with prominent nucleoli. Nuclear features of papillary carcinoma were present among both the cellular groups and scattered cells. The histologic examination showed a circumscribed papillary tumor comprising Hürthle cells and a brisk inflammatory component filling the stalks of papillae. These findings were consistent with a papillary Hürthle cells carcinoma with lymphocytic stroma, the so-called Warthin-like tumor of the thyroid. Hürthle cells admixed with inflammatory cells in cytology preparations can be seen in Hürthle cell nodules or neoplasms arising in a background of chronic lymphocytic thyroiditis. We suggest that a careful search for nuclear features may be helpful in diagnosing this variant of papillary carcinoma.     

Fine-Needle Aspiration Cytology of Papillary Hurthle Cell Carcinoma with Lymphocytic Stroma "Warthin-Like Tumor" of the Thyroid

Papillary Hurthle cell carcinoma with lymphocytic stroma is a recent addition to the list of variants of papillary carcinoma of the thyroid. We report the aspiration cytology and histology findings of this tumor arising in two patients. The smears were cellular, and revealed Hurthle cells arranged in three-dimensional groups, papillary fragments, and as singly dispersed cells with a prominent intimately associated inflammatory component of lymphocytes and few plasma cells. The Hurthle cells were pleomorphic and showed granular eosinophilic cytoplasm, eccentrically oriented nuclei with prominent nucleoli. Nuclear features of papillary carcinoma were present among both the cellular groups and scattered cells. The histologic examination showed a circumscribed papillary tumor comprising Hurthle cells and a brisk inflammatory component filling the stalks of papillae, These findings were consistent with a papillary Hurthle cells carcinoma with lymphocytic stroma, the so-called Warthin-like tumor of the thyroid. Hurthle cells admixed with inflammatory cells in cytology preparations can be seen in Hurthle cell nodules or neoplasms arising in a background of chronic lymphocytic thyroiditis. We suggest that a careful search for nuclear features may be helpful in diagnosing this variant of papillary carcinoma.     

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34βE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF^V600K mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.     

Primary mucoepidermoid carcinoma and sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland: a report of nine cases.

Mucoepidermoid carcinoma is a rare primary thyroid tumor with indolent biologic potential. Two types of tumors have been described under this category: mucoepidermoid carcinoma (MEC) and sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE). The MEC shows both squamous and glandular differentiation in a background of a noninflamed gland, whereas SMECE is characterized by extensive sclerosis, squamous and glandular differentiation, a concomitant inflammatory infiltrate rich in eosinophils, and a background of lymphocytic thyroiditis. We present nine cases of these entities: five MEC and four SMECE. All tumors occurred in women (age 27 to 73 years). Five tumors showed extrathyroidal invasion and multiple lymph node metastases. One case of MEC showed a concomitant tall cell variant of papillary carcinoma with vascular invasion, and two cases showed intimately associated areas of usual papillary carcinoma. One of the latter cases also showed areas of transformation to anaplastic carcinoma. In all cases of SMECE and in only one case of MEC, the uninvolved thyroid tissue showed lymphocytic thyroiditis. Follow-up information was available in four of the nine cases (3 months to 7 years). Two patients with SMECE are alive with no evidence of disease. One patient with MEC and tall cell variant of papillary carcinoma died of disease after 3 months, and the patient with anaplastic carcinoma died after 5 months with lung metastasis. Both MEC and SMECE were positive for cytokeratin and negative for calcitonin. All cases of MEC were positive for thyroglobulin, whereas all cases of SMECE were negative. The immunohistochemical findings suggest that both MEC and SMECE have different histogenesis.     

Fine-needle aspiration in the evaluation of thyroid lesions in children

The role of fine-needle aspiration (FNA) cytology in the evaluation of thyroid lesions in not as well established in children when compared with adults. Hence we aimed to ascertain the utility and limitations of FNA in childhood thyroid lesions. This was a retrospective analysis of all thyroid FNA performed in children less than 14 years of age over a 4-year period (2005-2009). Histopathological follow-up was available in six cases. A total of 77 cases were included in the analysis. The most common cytological diagnosis was lymphocytic thyroiditis (49.3%), followed by colloid goiter (18.2%), hyperplasia (10.4%), and benign aspirate (7.8%); malignancy was identified in six cases (7.8%). Of these six cases, three were papillary thyroid carcinoma. There was one false-positive case reported as a Hurthle-cell neoplasm, which on histology showed Hashimoto's thyroiditis. One case each of rhabdomyosarcoma and spindle epithelial tumor with thymus like differentiation was wrongly diagnosed as thyroid neoplasm, NOS, and medullary carcinoma (spindle variant), respectively. The overall diagnostic accuracy was 98.6% with 100% sensitivity, 98.6% specificity, 80% positive predictive value, and 100% negative predictive value. FNA is extremely valuable in the initial evaluation of thyroid swelling in children. Rare neoplasms masquerading as thyroid nodules in children can pose difficulties in diagnosis; however, papillary carcinoma is easily recognized. In lymphocytic thyroiditis, it provides a tissue diagnosis, thereby avoiding more invasive procedure for merely diagnostic purposes.     

Diffuse sclerosing variant of papillary carcinoma of the thyroid. A histopathological study of four cases

We present four cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in Japanese women ranging in age from 17 to 42 years. Macroscopically, both lobes of the thyroid were involved, being diffusely enlarged and firm. Histologically, the tumor was characterized by squamous metaplasia of tumor cells, numerous psammoma bodies, extensive stromal fibrosis, severe lymphocytic infiltration with formation of lymph follicles, and thin bundles of smooth muscle cells in the fibrous stroma. The tumor islands were located mainly within the dilated lymphatic vessels and the metastatic tumor involved the bilateral cervical lymph nodes in all cases. It is assumed that papillary carcinoma of this type invades the thyroid lymphatics during the early stage and, without forming nodular lesions, disseminates to both lobes with extensive metastasis to the cervical lymph nodes. It should be noted that papillary carcinoma of this type often suggests chronic thyroiditis clinically because of the symmetrical enlargement of the thyroid and frequent positive anti-thyroid antibodies in the serum. Some workers have reported the prognosis to be unfavorable because of extensive lymphatic involvement, but the prognosis of this variant has not yet been defined.     

Encapsulated follicular variant of papillary thyroid carcinoma with bone metastases.

Although true follicular thyroid carcinoma is known to metastasize via the bloodstream and give rise to bone and lung metastases, such a pattern of spread is rare in papillary thyroid carcinoma. The follicular variant of papillary thyroid carcinoma (FVPTC) is believed to behave in a clinical manner similar to usual or classical papillary cancer and to follow a similar indolent course. There have been a few reports of "aggressive" FVPTC wherein follicular patterned tumors with nuclear features of papillary carcinoma have metastasized hematogenously; these neoplasms have been diffusely invasive or multicentric in the thyroid. We report five cases of FVPTC, which were encapsulated and simulated grossly and microscopically follicular adenomas. In two of these, the primary was discovered after clinical presentation of bone metastases. In three others, bony metastases (without other nonosseous metastases) arose 7 to 17 years after thyroid lobectomy for lesions initially diagnosed as follicular adenoma In retrospect, these three encapsulated lesions had vascular invasion. We wish to bring attention to these innocuous-appearing lesions, which, although sharing nuclear features of papillary cancer, behave clinically in an unexpectedly malignant fashion.     

Multiple brain metastases from a diffuse sclerosing variant of papillary carcinoma of the thyroid

We report a 53-yr-old man who presented with multiple brain metastases from a diffuse sclerosing papillary carcinoma of the thyroid. The presenting clinical features were those of an intracranial space-occupying lesion. Three brain tumors, confirmed pathologically to be metastatic thyroid papillary carcinomas, were removed. Two weeks after craniotomy, total thyroidectomy with cervical lymph node dissection was performed. Both lobes of the thyroid were diffusely enlarged and firm with a dominant mass. Histologically, the tumor was characterized by a combination of bilateral diffuse involvement of the gland, marked fibrosis, squamous metaplasia, abundant psammoma bodies, lymphocytic infiltration, frequent lymphatic and blood vessel permeation of the tumor, and typical elements of a conventional papillary carcinoma. In addition to these histologic findings, elements of other papillary carcinoma variants such as follicular and tall cell variants were also found focally. Twenty-three of twenty-four resected bilateral lymph nodes showed metastases of papillary carcinoma. Although the diffuse sclerosing variant of papillary carcinoma of the thyroid seems to be recognized as an aggressive variant of papillary carcinoma, there is no previous report of brain metastasis from this variant.     

The association between chronic lymphocytic thyroiditis and thyroid tumors

An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.     

Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions

CONTEXT: The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN: We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS: Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION: We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.     

Diffuse sclerosing variant of papillary thyroid carcinoma: A clinicopathologic and immunophenotypic analysis of 22 cases

Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon tumor making up about 2% of all papillary thyroid carcinomas. Previous studies have not comprehensively evaluated these tumors in a large series of patients. Design: Twenty-two cases of DSV-PTC diagnosed between 1970 and 2000 were identified in the files of the AFIP. Histologic and immunohistochemical features were evaluated and patient follow-up was obtained. Results: The tumors affected 14 females and 8 males, aged 6 to 49 yr (mean, 18 yr), with males presenting at a mean older age than females (24 vs 14 yr). Symptoms included an enlarging mass in the thyroid, present for a mean of 9.5 mo. While a dominant tumor was identified in a single lobe, bilateral disease was common (n=16). The dominant mass ranged in size from 1.7 to 5.8 cm in diameter (mean, 3.8 cm). Histologically, all cases demonstrated a papillary carcinoma (conventional, solid, or follicular pattern) diffusely involving the gland. Extrathyroidal extension, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis/sclerosis, and psammoma bodies were present to a variable degree. Both the papillary carcinoma and squamous metaplasia cells were strongly immunoreactive with CK19, thyroglobulin, and TTF-1. An increased number of S-100 protein immunoreactive dendritic cells were recognized. p53 was increased (>15%) in the tumor cells in 12 patients, while Ki-67 was increased in the tumor cells in two patients. Perithyroidal and cervical lymph node metastasis occurred in 18 (82%) patients. All metastases demonstrated histologic features similar to the primary. Complete resection (thyroidectomy in 18 patients) with lymph node dissection, yielded a 95% 5-yr survival without evidence of disease. One patient died of disease after a malignant transformation of the squamous metaplasia into squamous cell carcinoma. Conclusions: The recognition of DSV-PTC can be made with the following features: classic to solid foci of PTC, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis, and innumerable psammoma bodies. DSV-PTC is more biologically aggressive than conventional PTC, but the patients’ survival is not significantly different. This diagnosis should lead the clinician to aggressively manage these patients (thyroidectomy and lymph node dissection) in an effort to achieve an excellent long-term clinical outcome.     

Up-regulation of cyclooxygenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase

To cast light on relations of cyclooxygenase-2 (COX-2) expression to lymphocytic thyroiditis and thyroid tumorigenesis, protein levels were immunohistochemically assessed and compared with inducible nitric oxide synthase (iNOS) in a total of 181 cases: follicular adenoma, 23; well-differentiated papillary carcinoma, 85; poorly differentiated papillary carcinoma, 25; anaplastic carcinoma, 7; and follicular carcinoma, 41. In addition, 72 specimens of normal follicular epithelia and 36 of lymphocytic thyroiditis were used as control samples. Immunohistochemical results were confirmed in 2 cases each of normal thyroid, lymphocytic thyroiditis, and well-differentiated and poorly differentiated papillary carcinoma, by Western blotting assay. Stepwise increments in overexpression of COX-2 and iNOS were revealed in epithelial cells of lymphocytic thyroiditis, follicular adenoma, and papillary carcinoma; normal thyroid epithelium showed little expression. A significant positive correlation between the 2 enzymes was found with all cases. Enhanced expression of both COX-2 and iNOS suggests important roles in the inflammatory processes underlying lymphocytic thyroiditis and thyroid tumorigenesis.     

Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant

Mutation of the BRAF gene is common in thyroid cancer. Follicular variant of papillary thyroid carcinoma is a variant of papillary thyroid carcinoma that has created continuous diagnostic controversies among pathologists. The aims of this study are to (1) investigate whether follicular variant of papillary thyroid carcinoma has a different pattern of BRAF mutation than conventional papillary thyroid carcinoma in a large cohort of patients with typical features of follicular variant of papillary thyroid carcinoma and (2) to study the relationship of clinicopathological features of papillary thyroid carcinomas with BRAF mutation. Tissue blocks from 76 patients with diagnostic features of papillary thyroid carcinomas (40 with conventional type and 36 with follicular variant) were included in the study. From these, DNA was extracted and BRAF V600E mutations were detected by polymerase chain reaction followed by restriction enzyme digestion and sequencing of exon 15. Analysis of the data indicated that BRAF V600E mutation is significantly more common in conventional papillary thyroid carcinoma (58% versus 31%, P = .022). Furthermore, the mutation was often noted in female patients (P = .017), in high-stage cancers (P = .034), and in tumors with mild lymphocytic thyroiditis (P = .006). We concluded that follicular variant of papillary thyroid carcinoma differs from conventional papillary thyroid carcinoma in the rate of BRAF mutation. The results of this study add further information indicating that mutations in BRAF play a role in thyroid cancer development and progression.     

Diffuse sclerosing variant of papillary carcinoma of the thyroid. Report of three cases.

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.     

Diffuse Sclerosing Variant of Papillary Carcinoma of the Thyroid Report of Three Cases

Three cases of an unusual diffuse sclerosing variant of papillary carcinoma were found among 370 consecutive malignant tumors of the thyroid gland retained in the surgical pathology files of Kanazawa University Hospital over the last 10 years. The tumors were characterized by diffuse involvement of one or both lobes of the thyroid, dense fibrosis, papillary carcinoma with marked squamous metaplasia and abundant psammoma bodies, heavy lymphocytic infiltration and extensive lymphatic permeation. In two cases, the neoplasms showed more aggressive regional lymph node metastases and local invasion; the patient in the first case underwent surgery three times after initial radical surgery because of regional lymph node recurrences, and the second case showed direct invasion of the thyroid tumor to the larynx and distant metastasis to the lungs. Although the number of examined cases was small, the findings suggest that the diffuse sclerosing variant type has a less favorable prognosis and should be differentiated from papillary carcinomas with excellent prognosis.     

Tumor-to-tumor metastasis to follicular variant of papillary carcinoma of thyroid.

OBJECTIVE: To describe and document tumor-to-tumor metastases in the thyroid gland. METHODS AND RESULTS: In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19. CONCLUSIONS: Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.     

Differential expression of cytokeratins in follicular variant of papillary carcinoma: an immunohistochemical study and its diagnostic utility.

The follicular variant of papillary carcinoma (FVPTC) is characterized by follicular growth pattern and tumor cells with appropriate nuclear features of papillary carcinoma. However, occasionally these lesions may show focal or multifocal instead of diffuse distribution of nuclear features of papillary carcinoma. Such lesions can be underdiagnosed as benign follicular nodule. Previous studies have shown that cytokeratins, especially 19, are helpful in differentiating papillary carcinoma from other benign and malignant follicular patterned lesions. In this study, we applied monoclonal antibodies to CK5/6/18, CK18, CK10/13, CK20, CK17, and CK19 to paraffin sections of formaldehyde-fixed tissue from 26 cases of FVPTC with multifocal distribution of papillary cancer nuclei, 10 cases of usual variant of papillary carcinoma, 1 case of Warthin's tumor-like papillary carcinoma, and 2 cases of the columnar cell carcinoma. CK19 stained strongly and diffusely all cases of papillary carcinoma. FVPTC cases showed strong staining of the areas with papillary cancer nuclei in all cases and moderate to strong staining in areas of tumor without obvious nuclear features of papillary cancer. Normal thyroid parenchyma adjacent to the tumor nodule showed focal staining in most cases; however, tissue away from the tumor nodule failed to show any staining. All cases of usual type of papillary carcinoma, 2 of columnar cell carcinoma, and 1 Warthin's tumor-like papillary carcinoma showed strong and diffuse staining with CK19 and failed to show any staining of adjacent normal thyroid parenchyma. Similar but less intense staining patterns were seen with CK17 and CK20. The control group, consisting of cases of follicular adenoma, follicular carcinoma, and hyperplastic nodule, showed no staining with CK19. We suggest that if one is using immunohistochemistry to aid in the diagnosis of cases of FVPTC with multifocal distribution of nuclear features of papillary cancer, an antibody panel comprising CKs 17, 19, and 20 may prove helpful. In addition, we hypothesize that the staining of adjacent nontumorous thyroid parenchyma with CK19, seen only in cases of FVPTC, suggests that some factors secreted/produced by this particular tumor may lead to modification in keratin expression of surrounding follicular epithelium.     

Intraepithelial Neutrophils in Thyroid Fine-Needle Aspiration: A Portent of Aggressive Thyroid Cancer?

We report three patients with papillary thyroid carcinoma in whom fine-needle aspiration (FNA) showed neutrophils within tumor cells. All three patients presented with large neck masses; at excision, two proved to be tall cell variants of papillary cancer. Nodal metastasis, extrathyroidal extension, and vascular invasion were found in both cases. One patient has experienced recurrent disease; the other has an increasing thyroglobulin titer but no clinically appreciable recurrence. The third patient refused further therapy, but brain metastases were noted clinically; this patient died of disease. In each case, FNA showed tumor clusters with characteristic nuclear features, papillary groups, and psammoma bodies. Neutrophils were present in the cytoplasm of tumor cells in the absence of necrosis. Immunostaining for proliferating cell nuclear antigen (PCNA), MIB-1 (Ki-67), and p53 tumor suppressor gene product was markedly positive. Intraepithelial neutrophils have not been previously reported in differentiated thyroid tumors. We postulate that these neoplasms produce specific leukocyte-attracting cytokines analogous to those produced by anaplastic and poorly differentiated thyroid carcinomas. We believe the finding of intraepithelial leukocytes in the absence of necrosis in thyroid FNA specimens represents a characteristic of clinically aggressive differentiated papillary neoplasms; in our small series, each represented a tall cell variant of papillary carcinoma.     

Bone metastases from thyroid carcinoma: a histopathologic study with clinical correlates

CONTEXT: Only limited information exists on the pathologic aspects of thyroid carcinomas with bone metastases, most large studies having concentrated mainly on their clinical features. OBJECTIVE: To study in detail the morphologic features of thyroid carcinomas with skeletal metastases. DESIGN: Seventy-nine cases of thyroid carcinoma with bone metastases treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1964 and 1998 were investigated, with emphasis on the pathology of the primary and/or metastatic tumors and comparison of the morphologic features of the tumors at both the sites, wherever possible. The tumors were also compared for various clinical parameters. RESULTS: The cohort consisted of 22 papillary, 17 follicular, 16 insular, 10 anaplastic, 9 Hürthle cell, and 5 medullary carcinomas. Of these cases, 68% had poorly differentiated or undifferentiated features in the primary and/or metastatic tumors. The metastatic tumors were better differentiated than the primary in one third of the cases (6 of 18). Only one case showed a less differentiated metastasis. The overall 5- and 10-year survival probabilities after the bone metastases were 29% and 13%, respectively (Kaplan-Meier method). Although both the tumor type and differentiation seemed to affect survivals after bone metastasis (P =.007 and.012, respectively) (log-rank test), this was primarily due to the much worse prognosis in the cases of anaplastic and medullary carcinoma. Cases of Hürthle cell carcinoma showed the longest median survival. There was no significant difference in survival among patients up to or older than 45 years at the time of metastases (P =.31). CONCLUSIONS: Most thyroid carcinomas with bone metastases are of papillary type, and most have poorly differentiated or undifferentiated features. The influence of the microscopic tumor type and tumor differentiation on survival after bone metastasis primarily appears to be due to the much worse prognosis among anaplastic and medullary carcinomas. Age at diagnosis of bone metastases does not influence survivals.