Follicular thyroid adenoma dominated by spindle cells: report of two unusual cases and literature review

Primary spindle cell neoplasms of the thyroid gland are quite rare. They encompass a heterogeneous group of benign and malignant lesions of mesenchymal and epithelial origin. We herein describe two unusual follicular thyroid adenomas dominated by spindle cells with occasional areas of colloid-forming follicular differentiation. The tumors affected a 77-year woman and a 70-year old man; both had a long-history of monoclonal gammopathy of unknown significance (MGUS). One tumor presented as a large cold thyroid nodule and the other was an autopsy finding. The tumors were predominantly composed of fibroblast-like spindled cells. One case showed prominent meningioma-like concentric perivascular arrangement and contained cytoplasmic melanin-like pigment. Stromal hyalinization was a prominent feature of both. By immunohistochemistry, the spindled cells expressed vimentin, pankeratin (KL1), thyroglobulin and TTF1 consistent with a follicular differentiation. They did not stain with calcitonin, CEA and other lineage-specific mesenchymal, neuroendocrine and melanocytic markers. There was no evidence of metastasis at autopsy (case 2) or at last follow-up 2 years after surgery (case 1). These cases demonstrate the diversity of follicular thyroid neoplasms and the unusual occurrence of extensive spindle cell metaplasia. These uncommon lesions need to be distinguished from spindle cell medullary carcinoma, paucicellular spindle cell anaplastic carcinoma, spindle cell foci in papillary and follicular carcinoma, solitary fibrous tumor and other rare benign and malignant mesenchymal lesions.     

Mucoepidermoid Carcinoma of the Thyroid with Concomitant Papillary Carcinoma: Comparison of Findings on Fine-Needle Aspiration Biopsy and Histology

We report two cases of mucoepidermoid carcinoma (MEC) of the thyroid gland coexisting with, and possibly arising in, papillary thyroid carcinoma (PTC). In the first case, CT-guided fine-needle aspiration (FNA) was performed on a paratracheal mass representing extrathyroidal invasion of a right thyroid lobe tumor. The aspirate showed papillary fronds and cells in honeycombed arrangements with fine chromatin, enlarged nuclei, nuclear grooves, and intranuclear inclusions in a background of mucus and blood; a diagnosis of PTC was rendered initially. However, examination of histologic sections of the mass showed nests of malignant squamous cells with interspersed mucous cells and extracellular mucin, concordant with MEC, as well as PTC. A retrospective review of the FNA specimen identified MEC. In the second case, ultrasound-guided FNA was performed on a right thyroid lobe nodule. The aspirate contained two populations of epithelial cells: larger cells showing foci of both squamous and glandular differentiation that were interpreted as MEC and smaller follicular cells with nuclear changes characteristic of PTC; both were addressed in the diagnostic report. Primary MEC of the thyroid is a rare neoplasm typically exhibiting indolent clinical behavior, although our first case demonstrated extensive local invasion. It is thought to arise from squamous metaplasia associated with PTC, Hashimoto thyroiditis, or other inflammatory or neoplastic processes. In thyroid FNAs, the presence of neoplastic mucous cells and extracellular mucin plus malignant squamous cells is diagnostic of MEC. As MEC is thought to arise in PTC, the finding of the latter in these aspiration specimens is not unexpected.     

Spindle cell metaplasia of the thyroid arising in association with papillary carcinoma and follicular adenoma

Spindle cell proliferations of the thyroid have been described in association with reactive processes and aggressive malignant neoplasms. We describe spindle cell proliferations in 10 patients arising in association with papillary carcinoma and follicular adenoma. The spindle proliferations were 0.3 to 3.0 cm in size, constituted from 1% to 95% of the primary neoplasm, and were either admixed with the neoplastic elements or peripherally located within the primary tumor Cytologically, these proliferations showed bland-appearing spindle cells with fine chromatin and subtle nucleoli. Mitoses were rare, and inflammation was minimal. Immunostains showed reactivity with thyroglobulin, indicating their follicular origin. We believe it is important to recognize these metaplastic proliferations and distinguish them from aggressive malignant neoplasms.     

Pathology of Thyroglossal Duct: an Institutional Experience

Thyroglossal duct (TGD) is a developmental anomaly in which a remnant of the thyroid anlage is left in the neck during its descent from the foramen cecum of tongue to final pretracheal position. A persistent duct can lead to thyroglossal duct cyst (TGDC). Histologically, TGDC contains an epithelial lining of squamous or pseudostratified ciliated columnar epithelium and ectopic thyroid gland tissue in the duct wall. TGD-associated malignancy is rare, and the majority is papillary thyroid carcinoma (PTC). A total of 242 patients with a diagnosis of TGD-associated lesions were identified in our institute. Two hundred and seventeen cases were diagnosed as TGDC. Sixty-eight of 217 (31.3 %) cases of TGDC had ectopic thyroid tissue in the cystic wall. Thirty-nine cases had preoperative fine needle aspiration (FNA). Of these cases, 37 of 39 (94.9 %) demonstrated macrophages and 19 (48.7 %) also showed cells of squamous and/or columnar epithelial lining. Only two cases showed rare thyroid follicular cells. Thyroid carcinoma was identified in 18 of 242 (7.4 %) cases. All cases were diagnosed as PTC including 12 cases of classic PTC (66.7 %), 3 cases of follicular variant (16.7 %), 2 cases of tall cell variant (11.1 %), and 1 case of classic PTC with focal tall cell features (5.6 %). Nine cases had TGD component (either epithelial lining cysts or ectopic thyroid tissue). Ten patients also underwent total thyroidectomy (67 %). Of these patients, four had no tumor and one had an incidental medullary carcinoma. Five of 10 (50 %) cases had incidental PTC with a size range of 0.1–0.3 cm. Five patients had follow-up by imaging studies; no suspicious or nodular lesions were found in the thyroid. In conclusion, we report an institutional case cohort of 242 patients with TGD-associated lesions, including 217 TGDC and 18 cases of PTC. Only seven cases fulfilled the diagnostic criteria of TGD-associated PTC, i.e., the presence of components of TGD and a normal thyroid. In the remaining 11 cases, we could not differentiate with certainty between pyramidal primary thyroid PTC/Delphian node metastasis or TGD-associated PTC.     

Familiäre Karzinome der Schilddrüse

Approximately 5% of differentiated thyroid carcinomas with follicular cell differentiation, papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and 25–30% of medullary thyroid carcinoma (MTC) are hereditary. They occur either as part of a defined syndrome or are confined to the thyroid gland. Compared to their sporadic non-hereditary counterparts hereditary thyroid carcinomas generally develop earlier and regularly show multifocal tumour growth. With the exception of familial MTC, which is preceded by neoplastic C cell hyperplasia, no precursor lesions of hereditary thyroid carcinoma are known. In strong correlation with the localisation of the germline mutation of the RET protooncogene, familial MTC shows a distinct clinical course which allows precise clinical decision-making for prophylactic thyroidectomy to prevent invasive MTC. According to current knowledge prophylactic thyroidectomy of all other types of hereditary thyroid carcinoma is not justified.     

Papillary Thyroid Carcinoma Emerging from Hashimoto Thyroiditis Demonstrates Increased PD-L1 Expression,Which Persists with Metastasis

There is evidence that programmed death-ligand 1 (PD-L1) is expressed by thyroid follicular epithelium in thyroiditis, but the role of PD-L1 in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to determine whether (1) the presence of background chronic lymphocytic thyroiditis (CLT) or Hashimoto thyroiditis (HT) influenced the expression of PD-L1 in benign follicular epithelium or in PTC and (2) if PD-L1 expression in PTC persisted with lymph node metastasis. We performed immunohistochemistry (IHC) for PD-L1 on formalin-fixed paraffin-embedded tissues. We first studied five cases of unremarkable thyroid, five cases of CLT, and five cases of HT without carcinoma. We subsequently performed PD-L1 IHC on ten cases of PTC arising in normal thyroid, ten cases of PTC arising in CLT, and ten cases of PTC arising in HT. Whenever available, we evaluated corresponding synchronous lymph node metastases from all cases for PD-L1 expression. PD-L1 expression was increased (10–90%) in all five cases of HT, only minimal expressed (1–5%) in two of five cases of CLT, and not expressed in five cases of unremarkable thyroid. PTC arising in normal thyroid or CLT nearly uniformly lacked PD-L1 expression. In contrast, PTC arising in HT demonstrated significant PD-L1 expression, which persisted in corresponding lymph node metastases. Background non-neoplastic follicular epithelium in the HT cases also demonstrated PD-L1 expression. Thyroid follicular epithelium in HT demonstrates increased PD-L1 expression, and PTC arising in a background of HT shows increased PD-L1 expression, which is retained with metastasis.     

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.     

Spindle epithelial tumor with thymus-like differentiation of the thyroid (SETTLE):: Report of two cases (one associated with a parathyroid adenoma)

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor usually localized in the thyroid gland and perithyroid tissues. It is considered to arise from ectopic thymic tissue or branchial pouch remnants. It occurs more frequently in children and adolescents. We report 2 cases of spindle epithelial tumor with thymus-like differentiation localized in the thyroid gland, and 1 of them was associated with a parathyroid adenoma. We emphasize the need for a close and long-term follow-up in these patients.     

Thyroid pathologic findings in patients with Cowden disease

We describe the histologic findings in thyroid glands from six female and five male patients with Cowden disease. The patients were aged 9 to 43 years (mean age, 26 years). The salient thyroid lesions in this syndrome were multicentric follicular adenomas and adenomatous (parenchymatous, hyperplastic) nodules showing a wide range of nonspecific cytoarchitectural patterns. Multiple tiny cellular foci, so-called microadenomas, were also a feature. Specific lesions composed of oxyphil or clear cells, a tumor with features of hyalinizing trabecular adenoma, and an adenolipoma also occurred. Two cases showed a follicular carcinoma in addition to multiple benign follicular cell proliferations. The follicular carcinomas occurred at an older age and were larger in size than the clinically significant benign nodular lesions, suggesting tumor progression. All tumors showed thyroglobulin immunoreactivity and were negative for calcitonin. The histologic findings of a multiple adenomatous goiter or multiple follicular adenomas, particularly in children and young adults, should alert the pathologist and physician to the possibility of an inherited trait, such as Cowden disease, with its implications for family screening. The tumors are usually benign and well demarcated, but, because of multicentricity and increased risk of recurrence or progression to carcinoma, total thyroidectomy should be advocated.     

Coexistence of primary squamous cell carcinoma of thyroid with classic papillary thyroid carcinoma

Primary squamous cell carcinoma of the thyroid gland is very rare and its histogenesis is poorly defined so far. Although there have been some cases of squamous cell carcinoma with variant types of papillary thyroid carcinoma (PTC), the present case is the first primary squamous cell carcinoma with classic PTC to be reported. A 43‐year‐old woman presented with a 20 year history of neck mass. Neck ultrasound indicated a 6 × 4 × 3 cm large mass. The patient underwent total thyroidectomy. Histopathology indicated a well‐differentiated squamous cell carcinoma and squamous metaplasia in conjunction with classic PTC. On immunohistochemistry cytokeratin 7 was positive in papillary carcinoma and squamous metaplasia, thyroglobulin was positive only in papillary carcinoma, and p63 was positive in squamous metaplasia and squamous cell carcinoma. Postoperatively, the patient received 59.4 Gy adjuvant radiotherapy, hormonal therapy and radioactive iodine therapy. At 8 months after surgery the patient remained disease free.     

The Cytology of a Thyroid Granular Cell Tumor

Granular cell tumor (GCT) of the thyroid is rare. Before this report, only four cases of thyroid GCT have been reported, none of which presented a cytopathological examination. In this paper, we report the fine needle aspiration cytology and pathological analysis of a thyroid GCT from a 12-year-old girl who presented with a painless neck mass. The tumor cells were single, in syncytial clusters, or pseudofollicles, contained small round, oval, or spindle nuclei, indistinct nucleoli, and a large amount of grayish, granular fragile cytoplasm. The background contained granular debris and naked nuclei. A differential diagnosis of thyroid GCT with more frequent thyroid lesions containing cytoplasmic granules, including Hurthle cells, macrophages, follicular cells, and cells of black thyroid syndrome, was also performed.     

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.     

Tubular adenoma of the gallbladder with spindle cell metaplasia.

We report four cases of tubular adenoma of the gallbladder with spindle cell metaplasia. Three patients had solitary polyps in the gallbladder and the fourth had multiple (three) polyps. Only one patient who had a polyp of larger size had abdominal pain. Histologically, these tubular adenomas had characteristic morular foci composed of short spindle cells. These spindle cell components lacked intercellular bridges or cytoplasmic keratinization. Immunohistochemically, the spindle cells stained positively for one or more cytokeratins and negatively for vimentin, muscle actin and S-100 protein. Spindle cells are considered to represent the metaplastic component of the adenoma cells.     

Unusual metastases of papillary thyroid carcinoma: report of 2 cases

We present 2 cases of papillary thyroid carcinoma (PTC) with conventional morphology that metastasized to unusual sites. The first neoplasm was a PTC whose initial clinical manifestation was a large metastasis in the pancreas which mimicked a primary neoplasm. The mediastinal location of the thyroid gland was responsible for the delay in identification of the primary tumor. Eventually, the patient, a 72-year-old man, developed brain and vertebral metastases. The second case was that of a 58-year-old woman with a PTC with initial metastases in cervical lymph nodes; subsequently, the tumor spread to axillary lymph nodes and finally to the breast. Transformation to anaplastic spindle and giant cell carcinoma within the breast metastasis occurred 20 years after the primary thyroid tumor had been diagnosed and surgically treated. The metastatic anaplastic spindle and giant cell carcinoma contained rhabdoid inclusions further complicating identification. To the best of our knowledge, only 3 cases of PTC metastatic to the breast have been reported, none of them with anaplastic transformation. On the other hand, only 3 cases of PTC metastatic to the pancreas have been published, 2 of them of the tall cell variant, and in none of these cases were the first symptoms attributable to the metastasis. Brief comments about the differential diagnosis are included.     

Thyroid nodular lesion: analysis of cancer risk based on Kuma Hospital experience

It is a difficult question, whether it is malignant or not, when you follow up patients with thyroid nodular lesions. Cytological examination helps to solve this issue more accurately but a cancer risk still exists in patients with a negative cytology, non-diagnostic or suspicious follicular neoplasms. Analysis of cancer risk in patients with benign thyroid nodular lesions was carried out among 1044 cases who underwent thyroid surgery at Kuma Hospital, Kobe, Japan, in 2000. The purpose of this study was to provide evidence of cancer risk in those patients in Japan. Among the 356 cases with benign nodular lesions, 99 cases of papillary carcinoma were found in the thyroid parenchyma. Seventy-nine of the 99 cases were clinical cancer and were found preoperatively by cytology, while 20 out of 277 (7.22%) cases were found postoperatively as incidental carcinoma. The incidence of follicular carcinoma of a minimally invasive type in the index nodule was 22 out of 279 (7.89%) cases in patients who were surgically treated.     

Predictive Factors of Malignancy in Thyroid Nodules with a Cytological Diagnosis of Follicular Neoplasm

In cases of follicular neoplasm identified by thyroid fine-needle aspiration (FNA), surgery is required to achieve a precise diagnosis. We investigated potential clinical factors for the preoperative prediction of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm. We retrospectively reviewed the data of 97 patients who were diagnosed with follicular neoplasm by FNA and had undergone surgery at the Korea Cancer Center Hospital between April 2010 and April 2012. Age, sex, laboratory data (such as thyroid-stimulating hormone, free T4, thyroglobulin (Tg), and Tg antibody), and ultrasonographic findings were reviewed from the electronic medical records. Of 97 patients, 50 (51.5 %) were diagnosed with benign nodules, 16 (16.5 %) with follicular thyroid carcinoma (FTC), and 31 (32.0 %) with papillary thyroid carcinoma (PTC). In comparison with the features of benign nodules, FTC presented with a large nodule size, high serum Tg level, isoechogenicity, calcifications, and peripheral halo, whereas PTC exhibited traits similar to those of benign nodules, except for high serum Tg level and the presence of calcifications on ultrasonography. Therefore, a high serum Tg level (≥75 ng/mL) and calcification were the only significant predictive factors for malignancy in case of follicular neoplasm (p?<?0.01). Serum Tg levels and the presence of calcification on ultrasonography are important clinical features to predict malignancy in thyroid nodules with cytological diagnosis of follicular neoplasm.     

Leiomyosarcoma: A Rare Tumor of the Thyroid

Primary leiomyosarcoma of the thyroid gland is uncommon. To date, 20 cases have been reported in English in the literature. The tumors usually present in elderly patients with female predilection and are associated with poor clinical outcome. Herein, we report an additional case of primary thyroid leiomyosarcoma in a 64-year-old woman. She underwent total thyroidectomy and later was discovered to have multiple lung and liver metastases. The patient died 3 months after surgery. The major differential diagnoses including undifferentiated (anaplastic) carcinoma of the thyroid, spindle cell variant of medullary thyroid carcinoma, spindle cell tumor with thymus-like differentiation, uncommon primary tumor of the thyroid and metastatic tumors with predominant spindle cells are discussed.