Cytology of Hürthle cell neoplasms of thyroid gland

Hürthle cell neoplasms (HCN) are an uncommon group of tumors of the thyroid gland. Fine needle aspiration cytology (FNAC) is an important diagnostic tool in solitary nodules of the thyroid gland. A 5-year retrospective analysis of all cases diagnosed as HCN on cytology was performed and correlated with the corresponding histopathology wherever available. There were 13 cases diagnosed as HCN out of which 6 cases had subsequent histopathologic examination. Four were adenomas and two were carcinomas. In addition, 3 cases that were adenomas on histopathology were reported on cytology as colloid goiter with cystic degeneration in 2 cases and as follicular adenoma in 1 case. There was extensive cystic degeneration in the former two cases whereas poor cellular preservation led to misdiagnosis in the third case. There were no specific cytomorphological features that distinguished adenoma from carcinoma. FNAC has a high specificity for a diagnosis of HCN, but the sensitivity is not as high because of sampling error.     

Fine-needle aspiration cytology of Hürthle cell carcinoma of the thyroid

Specific criteria for the diagnosis of fine-needle aspiration (FNA) of Hürthle Cell Carcinoma (HCC) have rarely been discussed in the literature. A retrospective review of 35 FNA cases with the diagnosis of Hürthle cell lesion or Hürthle cell neoplasm was performed. In each case, there was a subsequent surgical excision. The FNA specimens were divided according to histologic diagnoses as HCC (12 cases), Hürthle cell adenoma (HCA) (14 cases), and benign nonneoplastic Hürthle cell lesions (BNHCL) (9 cases). Each case was examined using a semiquantitative scoring system for the following 11 features: presence or absence of colloid, lymphocytes, and transgressed blood vessels (each scored 0 or 1); the percentage of nuclear enlargement, small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion (each scored 0-3); and age, gender, and size of lesion. When diagnosed by FNA as either Hürthle cell neoplasm or Hürthle cell lesion, males were much more likely to have malignant tumors than females. Statistically significant cytologic features that favored malignant (HCC) over benign lesions (HCA and BNHCL) included small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion. The presence of colloid and lymphocytes favored a benign lesion. Nuclear enlargement and large tumor size are significantly more common in neoplasms than BNHCL.     

Combined tall cell carcinoma and Hürthle cell carcinoma (collision tumor) of the thyroid

Tall cell carcinoma and Hürthle cell carcinoma are 2 aggressive forms of differentiated follicular-derived thyroid carcinomas. We present a case where these malignant tumors of thyroid coexisted. The tumor originated in the thyroid as a mixed tumor and metastasized as a tall cell tumor to the lymph nodes and as a Hürthle cell carcinoma to lungs. The coexistence of these tumor types is rare and sheds light on the histogenesis of Hürthle cell tumors and the metastatic behavior of combined tumors.     

Psammomatous calcifications in thyroid oncocytic (Hürthle cell) follicular tumors

Concentric calcifications, also known as psammoma bodies, are a relatively frequent finding in certain types of tumors, particularly papillary thyroid carcinoma (PTC). In the thyroid, they have been assigned a significant role in the diagnosis of PTC and in distinguishing between these tumors and other types of thyroid neoplasms. Concentric calcifications have also less commonly been noted in other processes in the thyroid, such as in tumors characterized by cells containing abundant oxyphilic cytoplasm (i.e., Hürthle cells). We have studied 12 patients with oncocytic thyroid follicular tumors that contained scattered psammomatous calcifications that led to difficulties in diagnosis. The patients were 9 women and 3 men, aged 34 to 63 years. 10 cases corresponded to benign, non-invasive oncocytic tumors and 2 cases were minimally invasive follicular carcinomas of oncocytic (so called Hürthle cell) type. The psammomatous calcifications were randomly scattered throughout the lesions and were present as a focal, incidental finding in 8 cases and were diffuse in 4 cases. They were composed of concentrically laminated deposits of dense basophilic material closely resembling psammoma bodies, often associated with more homogeneous deposits of lightly eosinophilic material without concentric lamination that were interpreted as precipitated thyroglobulin. Seven patients with clinical follow-up, including one with minimally invasive carcinoma, were alive and well between 5 and 12 years after diagnosis. Concentric laminated calcifications may be encountered in oncocytic (Hürthle cell) follicular tumors and should not be interpreted as indicative of PTC in the context of oncocytic neoplasms of the thyroid.     

Absence of the BRAF and the GRIM-19 mutations in oncocytic (Hürthle cell) solid cell nests of the thyroid

We report the first case of oncocytic solid cell nests (SCNs), found in the right lobe of the thyroid of a 70-year-old man. Conventional SCNs and 1 papillary microcarcinoma (mPTC) were also found in the left lobe. In the oncocytic SCNs, 80% of the main cells showed oncocytic cytoplasm immunoreactive for porin and proteins of the SDHB and SDHA genes. Positivity for cytokeratin 19, p63, galectin-3, and HBME-1 and negativity for thyroglobulin, thyroperoxidase, vimentin, Oct-4, and α-fetoprotein were found in oncocytic and conventional SCNs. An inverse correlation was found between oncocytic metaplasia and p63. Association with C cells was confirmed at protein and messenger RNA levels in both types of SCNs. No germinal mutation of GRIM-19 was detected. No somatic BRAF mutation was found in any of the SCNs nor in the mPTC. We conclude that SCNs may acquire mitochondrial alterations similar to those seen in follicular and C cells, as well as in their respective tumors.     

Hürthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis and clinical significance

The etiopathogenesis and the classification of oncocytic (Hürthle cell) tumors of the thyroid is reviewed with an emphasis on the role played by mitochondrial and nuclear genetic abnormalities that interfere with mitochondrial function. Oxyphilia is classified into primary or secondary and the so-called Hürthle cell carcinoma is divided into oncocytic (Hürthle cell) variants of papillary and follicular carcinoma.     

Molecular pathology of papillary, follicular and Hürthle cell carcinomas of the thyroid

In the review some of the molecular alterations that can relate to the neoplastic development of well differentiated thyroid carcinomas (follicular and papillary carcinoma) and of the so-called Hürthle cell carcinomas are described. Diagnostic and/or prognostic significance of the most recent findings is discussed.     

A delayed fatal metastatic Hürthle cell carcinoma

Hürthle (oxyphilic or oncocytic) cell carcinoma is a variant of follicular cell carcinoma of thyroid. Although this entity of thyroid cancer is well known, its occurrence in young patients has scarcely been reported. We report a case of a 26 year-old male patient, at the time of diagnosis, of Turkish origin, who developed a tracheal, pulmonary and mediastinal metastatic Hürthle cell carcinoma with bilateral cervical and mediastinal lymphadenopathies. This case illustrates an aggressive and metastatic cancer at the time of diagnosis and resistant to all treatment options including surgery, chemotherapy and radioactive iodine.     

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.     

Benign Hürthle cell adenoma with papillary architecture: a benign lesion mimicking oncocytic papillary carcinoma

We studied the significance of encapsulated Hürthle cell thyroid nodules with papillary structures lacking the nuclear features of papillary thyroid carcinoma (PTC); 19 cases fulfilling these criteria were encountered The patients' ages ranged from 22 to 40 years (32+/-6), and the F:M ratio was 3:1 The tumors measured from 0.5-5 cm (2+/-1.1). The diameter of the tumor cell nuclei ranged from 5.6 to 7.2 microns. Many nodules had nuclei displaying a fine chromatin pattern somewhat resembling those of PTC, but these were present in <20% of the tumor cells. Immunohistochemically, there was reactivity for MIB-1 in the papillary structures, negativity to focally weak reactivity for HBME and galectin-3, and negativity to moderate diffuse reactivity for CK19. Clinical follow-up from 1 to 19 years revealed no evidence of metastases in any of the cases. It is unlikely that the papillary structures in the study cases represent degenerative changes in view of the proliferative activity we have demonstrated in them. In view of (1) the encapsulation and the uniformity of the constituent cells, (2) the negative or weak immunoreactivity for galectin-3 and HBME and negative to moderate immunoreactivity for CK19, and (3) the absence or paucity 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 oncocytic follicular adenoma (Hürthle cell adenoma). Recognition of this entity is important to avoid an overdiagnosis of oncocytic PTC.     

Differential diagnosis of oxyphilic (Hürthle cell) adenomas and carcinomas of the thyroid

Successful application of a double immunostaining of oxyphilic tumors with a specific antimitochondrial antibody and proliferative marker Ki-67 was made for the first time. Comparative study of proliferative activity did not show a statistically significant difference between Hurthle-cell adenomas and carcinomas. However, oxyphilic carcinomas had a statistically significant positive correlation between proliferative index and aggressive course of tumor, tendency to recurrence, high metastatic activity, tumor size, presence of necrosis and capsule penetration.     

Hürthle cell neoplasms

Hürthle cells (HC) are characterized by abundant granular eosinophilic cytoplasm containing accumulated dysfunctional mitochondria and large nuclei with prominent nucleoli. Based on the distinct clinicopathologic and molecular characteristics of Hürthle cell neoplasms (HCN), the 2017 Endocrine World Health Organization (WHO) moved to categorizing HCN as a separate group of tumors. Hürthle cell carcinomas (HCC) are now subclassified as minimally invasive, encapsulated angioinvasive, and widely invasive. HCC have a low rate of driver mutations associated with follicular thyroid carcinoma. Instead, these neoplasms are characterized by widespread loss of heterozygosity due to whole-chromosome alterations and a high rate of mitochondrial DNA mutations. Increased understanding of the genomic underpinnings of HCC has translated into improvements in molecular testing of HCN. This review will focus on clinical, cytologic, and histopathologic features of HCN, concentrating on diagnostic challenges and prognostic parameters. In addition, the molecular characteristics and molecular testing of HCN will be reviewed.     

Primary thyroid spindle cell tumors: spindle cell variant of papillary thyroid carcinoma?

Primary thyroid spindle cell tumors or spindle cell component in the thyroid tumors are very rare. The spindle tumor cells were positive for thyroid papillary carcinoma markers. So these tumors were diagnosed as spindle cell variant of papillary thyroid carcinoma (PTC). To further delineate clinico-pathological features of primary thyroid spindle cell tumors and discuss differential diagnosis, we reported a 67-year-old man with a mass in the right thyroid without clinical symptom. Microscopy revealed that an encapsulated tumor with lot criss spindle cells arranged in bundles. Nuclear grooves were easy to see and rare displayed pseudoinclusions. Immunohistochemical studied showed that the spindle cells were all strong positive for TTF-1, Pax-8, thyroglobulin. Rare follicular were seen in the periphery of the tumor near the thyroid tissue. The cells formed follicular but the spindle tumor cells were positive for pan-keratins. The pathological diagnosis was primary thyroid spindle cell tumors, suspected spindle cell variant of PTC. Primary thyroid spindle cell tumors were presence and without the unified name. The further reports and more discussion were need about these tumors.     

Differentiated thyroid carcinomas with vascular invasion: a comparative study of follicular,Hürthle cell and papillary thyroid carcinoma

AIM: Non-medullary thyroid carcinomas arise from follicular cells. The purpose of this study is to correlate clinical and pathological properties of these tumours with the rate of distant metastasis from a series of thyroid tumours excised at one institution. METHODS: A total of 311 non-medullary thyroid tumours were identified and divided into: 29 follicular carcinoma (FC), 12 Hürthle cell carcinoma (HC), 13 Hürthle cell papillary thyroid carcinoma (HPTC) with vascular invasion (VI), 32 papillary thyroid carcinoma (PTC) with VI and 225 PTC without VI. The mean follow-up was 6.5 years with a range of 1-17 years. The tumours were histologically subdivided into minimal or wide invasion for FC and HC and focal or extensive invasion for PTC and HPTC, and stratified according to status of VI. RESULTS: The rate of distant metastasis was similar for FC, malignant Hürthle cell tumours and PTC with VI, and increased with extent of invasion. VI was seen in 12% of all PTC and 0% of HPTC in this study. PTC without VI were associated with a much lower potential of distant metastasis, were smaller in size and occurred in patients of younger age than PTC with VI. In addition, there was a tendency for increased potential for distant metastases with increased tumour size and patient age for all groups of tumours in the study. Patient age and tumour size appeared to play a smaller role than that of VI in predicting distant metastasis. CONCLUSIONS: Our study suggests that the rate of distant metastasis relates to VI, patient age and tumour size, regardless of Hürthle cell, FC or PTC differentiation. PTC of large size, and in patients older than 45 years, have a high propensity for vascular invasion.     

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.     

Cytodiagnosis of benign and malignant Hürthle cell lesions of the thyroid by fine-needle aspiration biopsy.

Eighty-two Hürthle cell (HC) lesions of the thyroid with cytologic evaluation by fine-needle aspiration biopsy (FNAB) were reviewed. In 17 cases the FNAB was not diagnostic because the fine-needle aspirates (FNAs) were too scanty in cellularity. Among the remaining 65 lesions, there were 45 HC adenomas (HCAs), six non-neoplastic HC nodules (NHCNs), 10 primary HC carcinomas (HCCs), and four metastatic HCCs. Forty-four HCAs were diagnosed as HC tumor (HCT), and one HCA was wrongly diagnosed as medullary carcinoma. All six NHCNs were wrongly diagnosed as HCT. Of 10 primary HCCs, there were diagnosed as HCT and seven as suspected HCC. Four metastatic HCCs were correctly diagnosed. The FNAs from 38 HCAs and four NHCNs were predominantly composed of large monomorphic HCs with oval nuclei, inconspicuous nucleoli, and abundant, well-defined, granular cytoplasm present singly, in acinar arrangement, and in monolayered sheets of variable sizes. Nuclear pleomorphism and prominent nucleoli were noted in seven HCAs and two NHCNs. Occasional small syncytial tumor cell clusters (STCCs) were noted in six cases, and a few naked tumor cell nuclei (NTCN) were observed in 16 cases. The FNAs from 14 HCCs were hypercellular. In all cases tumor cells were relatively small and showed monomorphic or pleomorphic nuclei, prominent nucleoli, and ill-defined cytoplasm. STCCs of variable sizes were present in abundance in 10 cases, and numerous NTCN were noted in 12 cases. In two HCCs, the tumor cells with well-defined cytoplasm were present singly and in cohesive sheets, and no STCCs or NTCN were observed. Thus, the presence of small tumor cells with ill-defined cytoplasm and prominent nucleoli in syncytial clusters and abundant NTCN in the FNA of a thyroid nodule should alert the observer about the strong possibility of an HCC.     

Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasms detected by comparative genomic hybridization.

Thyroid oncocytic (Hürthle cell) neoplasms represent a distinct subset of follicular thyroid tumors characterized by abnormal accumulation of mitochondria, whose chromosomal abnormalities have never been systematically analyzed. We have used comparative genomic hybridization to investigate chromosomal DNA alterations in 11 thyroid oncocytic tumors (7 adenomas and 4 carcinomas). Unbalanced chromosomal DNA profiles were detected in 6 of 7 adenomas and 3 of 4 carcinomas, numerical chromosomal aberrations being the dominant feature. Comparative genomic hybridization findings are compatible with two separate groups of tumors with karyotypic abnormalities, one characterized by multiple chromosomal gains with polysomy of chromosomes 5 and 7, the other by loss of chromosome 2. Pathologic and clinical features were similar in the two groups with no difference observed between adenomas and carcinomas. Activating H-, K-, or N-Ras mutations are commonly detected in follicular adenomas and carcinomas of the thyroid gland. However, Ras mutational analysis demonstrated that only one of the tumors in this series, an oncocytic carcinoma with a balanced karyotype, had activating Ras mutations (at codon 13 of K-Ras). The lack of Ras mutations in the 9 oncocytic neoplasms exhibiting chromosomal aneuploidy indicates that numerical chromosomal abnormalities are independent of activating Ras mutations in oncocytic tumors.     

Large needle aspiration biopsy histology for preoperative selection of Hürthle cell thyroid nodules

Carpi A, Rossi G, Mechanick J I, Nicolini A, Camici M, Russo M A & Di Coscio G
(2011) Histopathology   59 , 892–896 Large needle aspiration biopsy histology for preoperative selection of Hürthle cell thyroid nodules Aims: To assess whether the large needle aspiration biopsy (LNAB) histological distinction between pure microfollicular nodules and mixed micro–macrofollicular nodules can assist preoperative selection of a Hürthle cell nodule (HCN) discovered by fine needle aspiration cytology (FNAC). Methods and results: In 24 HCN identified by preoperative FNAC, preoperative LNAB histology was compared with postoperative pathology. FNAC demonstrated seven benign HCN (negative), eight HCN with atypia (positive); seven suspected cancers with HC (positive); and two cancers with Hürthle cells (positive). LNAB showed mixed micro–macrofollicular hyperplastic features in 12 nodules (negative) and a microfollicular structure in 12 nodules (positive), two of which included findings of papillary cancer. Postoperative findings were benign (negative) in 16 patients and malignant (positive) in eight patients. The sensitivity and specificity for FNAC were 87.5% [seven of eight, 95% confidence interval (CI): 47.3–99.7%) and 37.5% (six of 16, 95% CI: 15.2–64.6%], respectively, and for LNAB were 87.5% (seven of eight, 95% CI: 47.3–99.7%) and 68.8% (11 of 16, 95% CI: 41.3–89.0%), respectively. FNAC results were significantly different from postoperative results (McNemar’s test, exact two‐sided P = 0.012), while LNAB results were not (McNemar’s test, exact two‐sided P = 0.219). Conclusions: These data suggest that LNAB histology is more accurate than FNAC cytology for the preoperative selection of HCN.