Occult papillary carcinoma of the thyroid with pulmonary lymphangitic spread diagnosed by lung biopsy

Summary Distant metastases from occult papillary carcinoma of the thyroid, which is defined as a tumor less than 15 mm in diameter, are extremely rare. A 21-year-old patient with miliary micronodular densities in both lungs is described, in whom pulmonary lymphangitic spread of occult papillary thyroid carcinoma was diagnosed by thransthoracic lung biopsy.Abkürzungen BAL bronchoalveolar lavage - TBB transbronchial biopsy     

Bilateral Thyroid and Ultimobranchial Medullary Carcinoma

The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.     

Medullary thyroid carcinoma metastatic to the pituitary gland: an unusual site of metastasis

We present a case of metastatic medullary thyroid carcinoma involving the pituitary gland of a 23-year-old woman with multiple endocrine neoplasia type 2b who presented with diabetes insipidus and visual loss. The diagnostic features, including cytomorphology and immunohistochemistry, used to differentiate pituitary adenoma from metastatic medullary carcinoma are discussed. Pituitary metastases and tumor-to-tumor metastases in this region are also highlighted.     

Histopathologic types and clinical behaviour of occult papillary carcinoma of the thyroid

On studying 182 papillary neoplasms of the thyroid, 32 nonencapsulated lesions were found to be occult papillary carcinomas (maximum diameter 1.5 cm); out of these 32 patients 18 cases of cervical lymph node metastases were observed. Histologically, 4 circumscribed microcarcinomas, 3 partially encapsulated carcinomas, and 25 occult sclerosing carcinomas were distinguished. The mean diameter of the 4 circumscribed tumours as compared to that of the remaining 28 lesions proved to be statistically significantly smaller, but no significant differences could be observed regarding the rate of lymph node metastasis. One occult sclerosing carcinoma showed a morphologic pattern different from the remaining cases--namely that it had an exclusively solid appearance in the primary lesion and also in its lymph nodes metastases. The follicle cell origin of this lesion was established immunohistochemically by patchy thyroglobulin synthesis. The excellent prognosis of the occult category of papillary thyroid carcinoma was confirmed by a follow-up (mean 7.7 years, range 1.1 to 16.3 years), in which only 2 instances of eradicable recurrent lymph node metastases within the group of occult sclerosing carcinomas were recorded.     

Dipeptidyl peptidase IV (DPP IV/CD26) staining predicts distant metastasis of 'benign' thyroid tumor

Because follicular thyroid carcinoma is extremely difficult to diagnose, several cases were encountered which have been rediagnosed as carcinoma due to distant metastasis. In the search for a method of correctly diagnosing 'benign' thyroid tumor, dipeptidyl peptidase (DPP) IV immunostaining was applied to 10 cases whose diagnoses had been corrected to follicular thyroid carcinoma because of distant metastases. The positive rate of immunostaining using paraffin sections in the rediagnosed follicular thyroid carcinoma group (7/10) was much higher than that of the control group (1/29), which consisted of 15 cases of follicular thyroid adenoma and 14 cases of nodular hyperplasia. These results suggested that pre- or postoperative DPP IV staining is useful for predicting distant metastasis of 'benign' thyroid tumor.     

Occult thyroid cancer discovered by fine-needle aspiration cytology of cervical lymph node: a report of three cases

Three cases of occult thyroid cancer measuring 10, 6, and 3 mm in diameter were discovered by fine-needle aspiration cytology of cervical lymph nodes. In these three cases, thyroid tumors were not palpable, and scintigraphic, echographic, and soft-tissue radiologic examinations demonstrated no abnormalities of the thyroid glands. Cytologically, the presence of intranuclear cytoplasmic inclusions, nuclear grooves, and colloid was characteristic in aspirated materials. Histologically, all three cases were diagnosed as papillary carcinoma. Fine-needle aspiration cytology of cervical lymph node was very useful to find occult carcinoma of the thyroid gland.     

Mucinous breast carcinoma metastatic to thyroid gland: Report of a case diagnosed by fine‐needle aspiration cytology

Mucinous breast cancer is a slow‐growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine‐needle aspiration, a 58‐year‐old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery.     

Incidentally detected liver metastasis of well-differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small-to-large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well-differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole-body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well-differentiated follicular carcinoma of the thyroid.     

Serum vascular endothelial growth factor-D levels correlate with cervical lymph node metastases in papillary thyroid carcinoma

The aim of this multicenter study was to evaluate the clinical relevance of serum vascular endothelial growth factor-D (VEGF-D) in papillary thyroid carcinoma (PTC). This prospective study consisted of 74 patients with primary PTC and 15 patients with benign thyroid nodules treated from 2008 to 2009. VEGF-D concentration was compared with patient clinicopathologic features and lymph node metastases. There was no significant difference in mean serum VEGF-D levels between the PTC and benign thyroid nodule groups. Within the PTC group, serum VEGF-D levels were significantly higher in patients with lymph node metastases than in patients without metastases (241.92 vs. 213.89 pg/ml, respectively; P = 0.035). Receiver operating characteristic curve analysis revealed that preoperative serum VEGF-D levels were predictive of lymph node metastases in the patients >45 years. Serum VEGF-D level that was correlated with the presence of cervical lymph node metastases in PTC patients might be a useful prognostic indicator.     

Black thyroid revisited: cytologic diagnosis in fine-needle aspirates is unlikely

We report four patients diagnosed with black discoloration of the thyroid gland at surgery and a fifth patient in which the "black thyroid" was an incidental finding at autopsy. The four patients diagnosed at surgery had prior fine-needle aspirations (FNA), which did not reveal any characteristic pigmentation. One patient presented with cervical lymph node metastases from a papillary microcarcinoma of thyroid. The second patient was diagnosed as a cellular adenomatoid nodule, and suppressive therapy was recommended. She elected to have surgery instead. The third patient underwent surgery because of an oxyphilic cell nodule, in a background of lymphocytic thyroiditis, in which a Hürthle cell neoplasm could not be ruled out. His aspirates were reviewed at two other institutions, and no diagnosis of black thyroid was entertained. The fourth patient had an adenomatoid nodule with cystic change and slightly atypical squamous metaplasia. She decided to have surgery, which revealed a black thyroid. Later, it was discovered that the patients had received minocycline for the treatment of acne. FNA does not seem to be a reliable method to diagnose black thyroid preoperatively. Although this is a striking operative finding, diagnosing it on FNA seems to be unlikely and also inconsequential.     

Heterotopic intrathymic thyroid tissue

Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is important to distinguish it from metastases of clinically undetected thyroid carcinoma because metastatic papillary thyroid carcinoma is often so well differentiated, simulating normal thyroid tissue. Described herein are histological findings of heterotopic intrathymic thyroid tissue that was incidentally identified in a woman with papillary thyroid carcinoma during histological examination of a radical neck dissection specimen. These findings emphasize that this rare incidence may occur and should be differentiated from metastatic papillary carcinoma. Histologically, the patient's intrathymic thyroid follicles were identical to the normal thyroid follicles, having flat cuboidal cells with uniformly small nuclei without nuclear grooves or inclusions. The follicular cells had a low Ki-67 labeling index close to zero, and immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the tumor cells in primary papillary thyroid carcinoma of the patient. To the authors' knowledge this is the first case report of intrathymic heterotopic thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid 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.     

Mucoepidermoid carcinoma of the thyroid

Clinical and morphological features of three cases of primary mucoepidermoid carcinoma of the thyroid are described. The tumours were composed of two cell types. One of these resembled squamous epithelium and ultrastructurally showed tonofilaments and numerous desmosomes. The other cell type contained Alcian blue and mucicarmine positive mucin and, on electron microscopy, showed mucigen granules. Marked stromal fibrosis and psammoma bodies were seen in all tumours. Immunohistochemical studies showed that the tumour cells were negative for thyroglobulin. A few calcitonin-containing cells were seen in one metastatic tumour. One tumour showed, in addition to the histological features of mucoepidermoid carcinoma, anaplastic areas with obvious transition between the two histological patterns. The same thyroid also had a small thyroglobulin-positive papillary carcinoma in the opposite lobe. All tumours presented lymph node metastases. In two cases the primary tumour was confined within the thyroid capsule but that with anaplastic areas invaded surrounding structures. This patient died 13 months after diagnosis; the other patients are alive and symptomless one and 10 years since diagnosis. Mucoepidermoid carcinoma of the thyroid appears to be a clinicopathological entity that resembles papillary carcinoma in its natural history. The origin of the tumour is unclear. There is, however, some histological and immunohistological data suggesting that the tumour might be related to the ultimobranchial system although some histological features also appear to favour a common origin with papillary carcinoma.     

Clinicopathological and Molecular Histochemical Review of Skull Base Metastasis from Differentiated Thyroid Carcinoma

Skull base metastasis from differentiated thyroid carcinoma including follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) is a rare clinical entity. Eighteen FTC cases and 10 PTC cases showing skull base metastasis have been reported. The most common symptom of skull base metastasis from FTC and PTC is cranial nerve dysfunction. Bone destruction and local invasion to the surrounding soft tissues are common on radiological imaging. Skull base metastases can be the initial clinical presentation of FTC and PTC in the presence of silent primary sites. The possibility of skull base metastasis from FTC and PTC should be considered in patients with the clinical symptoms of cranial nerve dysfunction and radiological findings of bone destruction. A variety of genetic alterations in thyroid tumors have been identified to have a fundamental role in their tumorigenesis. Molecular histochemical studies are useful for elucidating the histopathological features of thyroid carcinoma. Recent molecular findings may provide novel molecular-based treatment strategies for thyroid carcinoma.     

Familial Non-Medullary Thyroid Carcinoma: An Update

Familial thyroid cancer can arise from follicular cells (familial non-medullary thyroid carcinoma (FNMTC)) or from the calcitonin-producing C-cell (familial medullary thyroid carcinoma). This is usually a component of multiple endocrine neoplasias (MEN) IIA or IIB, or as pure familial medullary thyroid carcinoma syndrome. The genetic events in the familial C-cell-derived tumors are known and genotype–phenotype correlations are well established. In contrast, the case for a familial predisposition of non-medullary thyroid carcinoma is only now beginning to emerge. Although the majority of papillary (PTC) and follicular thyroid carcinomas (FTC) are sporadic, familial tumors account for over 5% of cases. The presence of multifocal papillary carcinoma is a common feature of FNMTC. The familial follicular cell-derived tumors or non-medullary thyroid carcinomas encompass a heterogeneous group of diseases, including diverse syndromic-associated tumors and non-syndromic tumors. Based on clinico-pathologic findings, FNMTC is divided into two groups. The first includes familial syndromes characterized by a predominance of non-thyroidal tumors, such as familial adenomatous polyposis (FAP), PTEN hamartoma tumor syndrome (PHTS), Carney complex type 1, and Werner syndrome. The second group includes familial syndromes characterized by a predominance of NMTC, such as pure familial (f) PTC with or without oxyphilia, fPTC with papillary renal cell carcinoma, and fPTC with multinodular goiter. Some characteristic morphologic findings should alert the pathologist of a possible familial cancer syndrome, which may lead to further molecular genetic evaluation.     

Papillary thyroid carcinoma in Kanazawa, Japan: prognostic significance of histological subtypes

A retrospective analysis of 183 papillary thyroid carcinomas was made in order to assess the prognostic factors related to survival. The following factors were found to adversely affect the prognosis: trabecular subtype of papillary carcinoma, the extent of the primary tumour, regional lymph node involvement, the presence of distant metastases, old age, male sex and the extent of the neck dissection. The presence of the follicular variant of papillary carcinoma and the extent of the thyroidectomy did not influence the prognosis. The trabecular subtype of papillary carcinoma is characterized by a trabecular or solid arrangement of follicular cells with nuclei of ground-glass appearance. Univariate and multivariate analysis indicated that patients with this type of thyroid tumour had a poorer prognosis than those with the well-differentiated or follicular variants of papillary carcinoma. In our opinion the trabecular subtype of papillary carcinoma should be included as a separate entity in the WHO classification of thyroid tumours.     

Merkel cell carcinoma metastatic to the thyroid gland: Aspiration findings and differential diagnosis

Clinically diagnosed metastasis to the thyroid gland is exceptionally rare and may present diagnostic issues on fine needle aspiration. The most common primary sites of metastases to the thyroid are cancers of the lung, breast, skin (especially melanoma), colon, and kidney. Herein, we report a case of metastatic Merkel cell carcinoma to the thyroid presenting as a 2.1‐cm solid nodule in a 50‐year‐old male with a previous history of Merkel cell carcinoma of the upper extremity. The aspirates were moderately to highly cellular featuring small to intermediate sized cells with scant to no cytoplasm, round‐to‐oval nuclei with finely dispersed chromatin, and predominantly arranged as scattered single cells. There was focal nuclear molding, numerous mitoses, and karyorrhectic nuclei. The differential diagnosis centered on the “small round blue cell” tumor group such as medullary thyroid carcinoma and non‐Hodgkin lymphoma. However, in light of our patient's previous history, the FNA findings were most consistent with a metastasis of Merkel cell carcinoma. In patients with a known history of a primary neoplasm, the differential diagnosis of a thyroid nodule should always include potential metastasis. Diagn. Cytopathol. 2010;38:754–757. © 2010 Wiley‐Liss, Inc.     

Papillary Thyroglossal Duct Cyst Carcinoma with Synchronous Occult Papillary Thyroid Microcarcinoma

This is a case report on papillary thyroglossal duct cyst (TGDC) carcinoma along with synchronous occult papillary thyroid microcarcinoma. A 46-year-old woman visited our hospital because she had an anterior midline neck mass below her hyoid bone. Preoperative ultrasound-guided fine-needle aspiration cytology revealed signs of papillary TGDC carcinoma. We performed a Sistrunk operation and a total thyroidectomy. Histopathological examination of the specimen revealed papillary carcinoma arising in the TGDC and papillary microcarcinoma of the thyroid gland without extrathyroidal extension. Surgeons should be aware of TGDC carcinoma during surgical planning and postoperative treatment and should differentiate this carcinoma from an anterior midline neck mass.     

Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation

Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases, some of which are proven to be associated with aggressive clinical behavior such as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is recently described as a rare and aggressive variant of PTC. Herein, we are reporting a case of HVPTC in a patient who presented with hemoptysis and an intratracheal blood clot that was aspirated and submitted for cytopathological examination. Cytomorphology displayed neoplastic cells with profound micropapillary architecture, elongated nuclei, and prominent hobnail configuration. Nuclear features of PTC such as pseudoinclusions, nuclear overlapping, crowding, and grooves were readily identified. Subsequent total thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC is a rare locally aggressive subtype, which may present with metastasis from an occult thyroid primary. HVPTC needs to be included in the differential diagnosis of metastatic carcinoma with micropapillary architecture on fine needle aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754–756. © 2017 Wiley Periodicals, Inc.