Papillary carcinoma of the thyroid occurring during pregnancy. Report of a case diagnosed by fine needle aspiration cytology

A case of papillary carcinoma of the thyroid gland occurring during pregnancy in a 29-year-old woman is described. The enlarged thyroid nodule was first detected at 10 weeks of gestation; fine needle aspiration (FNA) of the nodule showed no cytologic evidence of malignancy. Repeat FNA at 30 weeks of gestation produced inadequate material for diagnosis. A final FNA at 38 weeks of gestation showed classic cytologic features of papillary carcinoma, including papillary structures, grooved nuclei and intranuclear cytoplasmic inclusions. After delivery, the patient was treated with total thyroidectomy and cervical lymph node dissection. The enlargement of the nodule in this case during the course of the pregnancy suggests a relationship between pregnancy and the malignant development of thyroid nodules; this is discussed along with the utility of FNA cytology for diagnosing thyroid cancers during pregnancy.     

Fine needle aspiration cytology and immunocytochemistry in a case of intrathoracic thyroid goiter

Fine needle aspiration (FNA) was performed in the case of a patient with an anterior mediastinal mass. Examination of the smears revealed individual and groups of benign nondiagnostic cells. Surgical removal and histologic examination indicated that the mass was a true intrathoracic thyroid goiter. Subsequent immunocytochemical studies on the FNA smears showed thyroglobulin in the cytoplasm of the aspirated cells. The cytologic findings are presented; while not diagnostic of a thyroidal origin in this case, they serve as a reminder of the wide range of cytologic appearances of colloid nodules and goiters. This case will hopefully heighten the awareness of cytologists and other physicians to the consideration of the possibility of intrathoracic goiter in the differential diagnosis of mediastinal lesions seen in fine needle aspirates.     

Cytology and mRNA expression analysis of fine needle aspirates of thyroid nodules in an East German region with borderline iodine deficiency.

Fine needle aspiration cytology (FNAC) is widely recommended as an important tool for pre-operative identification of malignancy in patients with nodular thyroid disease. To assess the diagnostic contribution of FNAC and the potential of quantitative mRNA analysis in fine needle aspirates in daily practice, we conducted a prospective study in thyroid clinics (n=2) and endocrine practices (n=3), respectively in an East German region with borderline iodine deficiency. Two-hundred and forty-four consecutive FNACs were obtained over a period of 2 years (2002-2004) from euthyroid patients presenting for first evaluation of a solitary thyroid nodule. The mean nodule size for FNAC was 27 mm (range: 10-79 mm). In 55% of patients FNAC was performed after scintiscan detection of a cold or normal functioning thyroid nodule (CTN), while in the remainder FNAC was performed as a primary investigation. FNAC outcomes were: 57.8% benign, 22.1% indeterminate, 2.5% suspicious for malignancy, 17.6% non-diagnostic. Messenger RNA levels for a house keeping gene (beta-actin) and a thyroid specific marker (thyroglobulin, Tg) were studied as basic molecular markers using real-time PCR. Both in the IN VIVO and EX VIVO FNA series, beta-actin and Tg mRNA levels were positively correlated with the thyrocyte cell yield/respective FNA smear. However, subgroup analysis showed that FNAC with histologically confirmed follicular thyroid cancer and/or microfollicular adenoma exhibited significantly lower Tg mRNA expression despite high beta-actin levels. Sufficient mRNA quantities were obtained in >90% of FNA specimen to allow quantitative mRNA analysis of at least 5 further genes. In conclusion, quantitative mRNA analysis is feasible in FNA on a routine basis and provides a perspective for a molecular distinction of thyroid nodules, once specific marker genes have been defined for benign and malignant thyroid tumours respectively.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.     

Diagnosis of thyroid metastasis of colonic adenocarcinoma by fine needle aspiration biopsy

A case of thyroid metastasis from colonic adenocarcinoma was diagnosed by fine needle aspiration (FNA) biopsy. The FNA specimen from the thyroid nodule contained tall columnar cells consistent with the intestinal primary. Staining of the tumor cells for thyroglobulin was negative. Histologic examination of the excised nodule, which was removed due to its rapid growth and risk of skin ulceration, confirmed the FNA diagnosis. FNA biopsy in such cases should be able to distinguish between a second primary neoplasm, which would be removed, and a metastasis, which would usually not be surgically treated.     

Do all Thyroid Nodules >4 cm need to be Removed? An Evaluation of Thyroid Fine-Needle Aspiration Biopsy in Large Thyroid Nodules

Objective: Controversy exists regarding the ability of fine-needle aspiration (FNA) biopsy to rule out malignancy when thyroid nodules exceed 4 cm in diameter. The goal of this study was to provide data regarding FNA accuracy in a clinical setting for detecting/ruling out malignancy in large thyroid nodules (≥4 cm) and discuss FNA utility in guiding surgical decisions.Methods: All thyroid FNA cases performed at Marshfield Clinic from 1/1/2000 to 12/31/2010 followed by complete or partial thyroidectomy on nodules of at least 4 cm were identified. Demographics, medical history, nodule biopsy characteristics, surgical procedures, and diagnosis data were abstracted. FNA was compared to histologic evaluation of surgical specimens.Results: A total of 198 patients with large thyroid nodules were identified. Most had a single large nodule, but ~40% were multinodular, and 206 total nodules were assessed. Females outnumbered males, and the mean age was ~50 years. After surgery, cancer was histologically identified in 49/206 (23.8%) nodules, including 9/123 nodules that had been categorized as benign by FNA, corresponding to a false-negative rate of 7.3%. Sensitivity/specificity for detecting malignancy by FNA was ~80%. The positive predictive value (PPV) was just below 60%, and the negative predictive value (NPV) was 93% but rose to 96% when papillary microcarcinomas were excluded.Conclusion: While FNA sensitivity in large nodules was relatively low, NPV was high, especially if incidental papillary microcarcinomas were excluded. When cancer prevalence and NPV are known, FNA can be a reliable “rule out” test in nodules ≥4 cm. This information is critical and can help guide the surgery decision, especially in high-risk patients. The decision for surgery should not be solely based on nodule size but should consider additional factors including cancer prevalence, clinical history, ultrasound features, surgical risk, and life expectancy.Abbreviations:FNA = fine-needle aspirationNPV = negative predictive valuePPV = positive predictive value     

Thyromegaly secondary to simultaneous papillary carcinoma and histiocytosis X. Report of a case and review of the literature

The cytologic and histologic findings are reported in a case of papillary carcinoma arising within a thyroid gland pathologically enlarged by histiocytosis X. Fine needle aspiration (FNA) biopsies of a thyroid nodule in a patient with longstanding histiocytosis X produced a scanty amount of colloid, a moderately dense mixed inflammatory infiltrate and numerous small papillary fragments lined by cuboidal-to-columnar cells. Both the inflammatory cells and the epithelial cells showed nuclear grooves; the two populations of neoplastic cells were distinguished, and the correct diagnosis of the nodule was made, by recognizing the greater amount of granular cytoplasm of the mononucleated Langerhans' cells. The rare involve-of the thyroid by histiocytosis X is reviewed; this case, which appears to be the first reported instance of the co-occurrence of histiocytosis X and papillary carcinoma of the thyroid, indicates that patients with histiocytosis X should be observed for the development of thyroid carcinoma and that FNA biopsy can make the distinction between the two conditions.     

Simultaneous occurrence of medullary and papillary carcinoma of the thyroid gland identified by fine needle aspiration. A case report

BACKGROUND: Fine needle aspiration (FNA) diagnosis of simultaneous medullary and papillary thyroid carcinoma in independent thyroid lobes is exceedingly rare. CASE: A 36-year-old female presented with a one-month history of dysphagia. Thyroid ultrasound revealed a multinodular goiter. She was clinically and biochemically euthyroid. FNA of the right thyroid nodule was consistent with medullary carcinoma, and FNA of the left thyroid lobe was consistent with papillary carcinoma. Immunohistochemistry revealed strong calcitonin and CEA positivity in the right lobe and lack of staining in the left lobe. Conversely, staining for thyroglobulin was negative on the right lobe and positive on the left lobe. CONCLUSION: The patient developed tumors in separate lobes of the thyroid. Immunoreactivity of calcitonin, CEA and thyroglobulin made a sharp distinction between the two tumors. Therefore, we conclude that these tumors were not linked by either embryology or genetics.     

Diagnostic pitfalls in the fine needle aspiration of thyroid nodules. A study of 555 cases in Chinese patients

The diagnostic value and limitations of fine needle aspiration (FNA) were determined by examining 555 palpable thyroid nodules in Chinese patients who had a definitive diagnosis established by thyroidectomy (529 cases) or large-needle biopsy (26 cases). Of the aspirates, 97.8% were satisfactory for cytologic examination. The overall malignancy rate was 20%. FNA detected 73 (74.5%) of 98 primary malignant tumors and 9 (90%) of 10 metastatic tumors. Diagnostic errors were most commonly due to inadequate specimens and cystic lesions. Cystic fluid, present in one-third of all lesions, was associated with a malignant nodule in 13% of the cases. FNA was most valuable for detecting papillary carcinomas; it may at times suggest the likelihood of a follicular carcinoma.     

Fine needle aspiration cytology of neuroblastoma, including peripheral neuroectodermal tumor, with immunocytochemical and ultrastructural confirmation

Eleven fine needle aspiration (FNA) biopsies were performed on seven children with neuroblastoma, including one patient with a congenital neuroblastoma and another with a peripheral neuroblastoma of the thoracopulmonary region. FNA cytology made the primary diagnosis of neuroblastoma in four of the seven cases. The other biopsies documented local recurrences and metastases to liver, lymph nodes, orbit and breast. The cytologic features included varying numbers of small primitive cells with scanty cytoplasm, poorly to well-formed pseudorosettes, cell processes, a fibrillary matrix and multinucleated ganglion cells. Five of the seven patients had electron microscopic (EM) examination of the FNA specimen, which in all cases confirmed the diagnosis. Batteries of immunoperoxidase stains were performed on all 11 aspirates with variable results. Staining for neuron-specific enolase was positive in four of the five neoplasms tested, although strongly positive in only three of the cases. Staining for neurofilament markers was positive in only two of five tumors. Studies for cytokeratin markers (AE1/3), low-molecular-weight cytokeratin (35BH11), hematopoietic markers (T29/33), immunoglobulin light chains and myoglobin were negative. One case was positive for vimentin. This study attests to the value of FNA cytology in suggesting a correct diagnosis of either primary, recurrent or metastatic neuroblastoma in children. Selective use of immunoperoxidase stains and EM on the aspirates may be of value.     

Fine needle aspiration of the hot thyroid nodule

The use of fine needle aspiration (FNA) cytology in the evaluation of solitary hot thyroid nodules was examined in 24 patients. Satisfactory FNA specimens were obtained from 22 patients. None of the cytologic samples was considered malignant or suspicious for malignancy. The cytologic findings were indeterminate in one instance--a smear with follicular features. The smears from the other 21 patients were judged to be benign. If FNA had been used as the initial diagnostic step, the need for a thyroid scan would thus perhaps have been avoided in 21 of the 24 patients. These results support the idea that FNA is the most effective procedure in the evaluation of the solitary thyroid nodule, whether functional or not.     

Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A case report

BACKGROUND: Renal cell carcinoma is an unpredictable tumor that can recur many years after the original diagnosis and metastasize to uncommon sites, including the thyroid gland. Differential diagnosis from primary thyroid tumor is often difficult both clinically and pathologically. We report a case of metastatic renal cell carcinoma in follicular adenoma of the thyroid gland. CASE: A 48-year-old woman presented with a 3-cm-diameter, palpable mass in the left lobe of the thyroid gland. The patient's history included removal of a left renal mass, which was conventional renal cell carcinoma. Fine needle aspiration cytology smears contained a few small clusters of polygonal cells with abundant, clear cytoplasm and irregular, hyperchromatic nuclei as well as bland-looking thyroid follicle cells and stromal cells. A papillary or follicular growth pattern was not detected. A cell block made from the aspirated sample was composed mainly of clear cells. By immunohistochemical stains, the clear cells were completely negative for TTF-1, thyroglobulin, calcitonin and inhibin while equivocally staining for cytokeratin, CD10 and galectin-3. The histologic diagnosis was renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. CONCLUSION: Renal cell carcinoma metastatic to the thyroid may masquerade as a primary thyroid neoplasm. A history of prior nephrectomy, the presence of unremarkable thyroid follicle cells, the absence of a papillary or follicular growth pattern and immunohistochemical study can help differentiating metastatic renal cell carcinoma from a primary thyroid lesion with clear cell change.     

Pulmonary metastases from intracranial meningioma diagnosed by aspiration biopsy cytology

A case of rare extracranial metastasis from a recurrent intracranial meningioma is described. Incidentally discovered asymptomatic pulmonary metastases were diagnosed as meningioma by transthoracic fine needle aspiration (FNA) biopsy. The aspirate contained spindle-shaped tumor cells and other forms that seemed to correspond to the fibroblastic, syncytial and angioblastic areas seen in the histologic sections of the primary tumor. Cytomorphologically, metastatic meningioma appears to be sufficiently distinctive to permit its cytologic differentiation from other spindle-cell tumors. Although meningiomas metastasize rarely, this diagnosis should be considered in the interpretation of a transthoracic FNA biopsy of a pulmonary nodule or nodules in a patient with a history of recurrent intracranial meningioma, especially when the aspirate mainly consists of spindle-shaped neoplastic cells.     

Primary squamous cell carcinoma of the thyroid diagnosed by fine needle aspiration cytology. A report of two cases.

BACKGROUND: Primary squamous cell carcinoma of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. CASES: Two males aged 65 and 68 years presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically malignancy was suspected. Fine needle aspiration (FNA) revealed numerous clusters and isolated malignant cells, dyskeratotic cells and deposits of eosinophilic granular keratin material. Subtotal thyroidectomy was performed. Histologic findings confirmed the cytologic diagnosis of squamous cell carcinoma. CONCLUSION: Primary squamous cell carcinoma of the thyroid is a rare tumor. FNA findings of this tumor were not reported before. FNA study cannot help to differentiate primary from metastatic squamous cell carcinoma of the thyroid.     

Fine needle aspiration cytology of granulomatous cryptococcosis of the lung

A cryptococcal infection was diagnosed in a patient with a history of immunoblastic non-Hodgkin's lymphoma by fine needle aspiration (FNA) cytology of a pulmonary nodule. This case illustrates that granulomatous inflammation can be appreciated by FNA cytology and, when seen, should result in a search for the specific organism. This case also reemphasizes the value of FNA cytology in the management and follow-up of patients with malignancy or those being treated with chemotherapy.     

Metastatic tumors in fine needle aspiration biopsy of the thyroid

A series of almost 25,000 thyroids examined by fine needle aspiration (FNA) biopsy was reviewed to ascertain the incidence and presentation of metastatic cancers in thyroid FNA samples. Metastatic cancers in FNA samples from the thyroid were identified in 25 cases (0.1%); the primary tumors were carcinomas of the kidney (8 cases), lung (7 cases), breast (5 cases), cervix uteri (1 case) and colon (1 case) and 1 case each of malignant melanoma, malignant pleural mesothelioma and rhabdomyosarcoma. FNA cytology was positive in all 25 cases. In 11 cases, the primary tumor was clinically known at the time of FNA biopsy; of the other 14 cases, cytology suggested that the malignancy was metastatic in only 5. Metastases of renal and mammary adenocarcinomas were almost indistinguishable from follicular and papillary thyroid carcinomas on cytologic grounds. The results demonstrate the rarity of this finding and the difficulty of diagnosing a metastatic tumor in the thyroid by FNA biopsy, in the absence of a clinical history of a prior primary neoplasm.     

Signet-ring follicular adenoma of the thyroid diagnosed by fine needle aspiration. Report of a case with cytologic description

BACKGROUND: Follicular cells of the thyroid may undergo squamous, oncocytic or clear cell metaplastic changes. Of these, the clear cell change with signet-ring formation is the most unusual, and follicular adenoma of the thyroid with signet-ring formation is extremely rare. We describe for the first time the cytologic features of a clear cell adenoma of the thyroid obtained by fine needle aspiration (FNA). CASE: A 48-year-old woman in a euthyroid state presented with a 2-cm, right-sided thyroid nodule. Smears obtained by FNA of the nodule revealed clusters of large signet-ring cells in a bloody background. The signet-ring cells were round to oval, with large cytoplasmic vacuoles and hyperchromatic, eccentric nuclei. Colloid in the background was very scanty. Histologic examination of the right hemithyroidectomy specimen revealed a signet-ring follicular adenoma. CONCLUSION: Lack of familiarity with signet-ring cell adenoma of the thyroid could lead to an erroneous diagnosis of metastatic signet-ring cell carcinoma.     

Immunocytochemistry in head and neck aspirates. Diagnostic application on direct smears in 16 problematic cases.

This report describes our experience with immunocytochemical staining of routinely processed smears in the fine needle aspiration (FNA) biopsy diagnosis of 16 tumors of the head and neck. Immunocytochemistry (ICC) was performed on alcohol-fixed or air-dried smears using commercially available monoclonal antibodies followed by a streptavidin-biotinylated peroxidase labeling method. In 12 aspirates with cytologically unclassifiable and undifferentiated cells, immunostaining for cytokeratin, leukocyte common antigen, S-100 protein and vimentin provided conclusive evidence of cell lineage. ICC permitted the correct identification and differential diagnosis of four additional tumors: a positive immunoreaction for thyroglobulin identified a metastatic Hürthle cell carcinoma of the thyroid; a coexpression of two distinct classes of intermediate filaments helped support the FNA diagnoses of a parathyroid adenoma and of a synovial sarcoma; and the double immunoreaction for CD15 and CD30 antigens helped identify Reed-Sternberg cells within an unusually suppurative harvest. Two immunostains were required for proper diagnosis in 13 cases and four in the remaining 3. In all cases but one only unstained slides were used. These data demonstrate that immunostaining can conveniently and advantageously be performed on direct smears of aspirated samples of head and neck lesions, but cases should be carefully selected for this procedure.     

Atypical epithelial cells, cannot exclude papillary carcinoma, in fine needle aspiration of the thyroid

OBJECTIVE: Atypical epithelial cells, cannot exclude papillary thyroid carcinoma (AEC-PTC), in fine needle aspiration (FNA) of the thyroid is a controversial diagnostic category that might cause a dilemma in patient management. STUDY DESIGN: Eighty-eight thyroid FNA specimens from 86 patients with a diagnosis of AEC-PTC were retrieved from our files in a 10-year period from December 1996 to December 2006. Of the 86 patients, 57 had follow-up histologic diagnoses and were included in this study. The cytologic and histologic materials were reviewed and correlated. RESULTS: Of the 57 patients, all had cytologic atypical features suggestive of PTC. Twenty-five cases of PTC were identified at surgery (44%). Review of the cytologic materials identified the following cytologic features, either alone or in combination strongly associated with PTC at resection: rare intranuclear cytoplasmic invagination (INCI), squamoid cytoplasm and psammoma bodies. CONCLUSION: The most common reasons for rendering the diagnosis of AEC-PTC in FNA of thyroid include rare atypical cells in a cystic thyroid nodule or a background of Hashimoto's thyroiditis. The cytologic features of LNCI, squamoid cytoplasm and psammoma bodies should alert the pathologist. Focal cytologic features of PTC in FNA samples are strongly associated with papillary carcinoma on resection.     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States