Thyroid cyst wall atypia in a patient with a history of malignant melanoma: A pitfall in fine‐needle aspiration cytology

We present an interesting case report from a patient with a history of desmoplastic malignant melanoma (MM), who presented with a thyroid nodule. The patient's clinical diagnosis included a benign thyroid nodule versus a primary thyroid malignancy or metastatic MM. Fine‐needle aspiration biopsy showed highly atypical spindle cells suspicious for metastatic MM. The acellular cell block prevented further studies such as immunohistochemical analysis. The patient underwent surgical excision of the mass, which showed a benign cystic thyroid nodule with an atypical cyst lining. Here, we report the presence of atypical cyst‐lining cells in a patient with diagnosis of MM. The atypical cytology of the cyst‐lining cells has been reported in the English literature; however, presence of significant cytological atypia, especially in a patient with a history of another malignancy, can be problematic. The cytopathologist should be aware of this entity and its diagnostic pitfalls. Diagn. Cytopathol. 2013;41:716–719. © 2013 Wiley Periodicals, Inc.     

Papillary thyroid carcinoma with atypical histiocytoid cells on fine‐needle aspiration

Although papillary thyroid carcinoma (PTC) usually has classic cytological characteristics on fine‐needle aspiration (FNA), it can present rarely with aberrant features resembling those of histiocytes in a cystic nodule. The aim of the current study was to describe PTC with atypical histiocytoid cells and distinguish it from benign histiocytes. A retrospective computerized search for FNAs with atypical features suggestive of PTC and cystic degeneration was performed, and if available, the corresponding resection specimens were compared. Four cases met the criteria for FNAs and three had surgical pathology follow‐up, which showed PTC. One aspirate had some features typical of PTC, but the remaining FNAs had atypical histiocytoid cells, which had traits intermediate between those of PTC and histiocytes. Large cell size, pseudoinclusions, nuclear grooves, and multiple well‐defined vacuoles in atypical histiocytoid cells favor PTC over benign histiocytes. Ancillary immunocytochemical studies can also be useful in confirming the diagnosis. Histiocytic cells are frequently present in thyroid aspirates, and occasionally, they have atypical features that represent an unusual presentation of PTC. Closer examination of these cells can provide diagnostic clues for preventing false‐negative diagnosis of PTC. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Histiocytic aggregates in benign nodular goiters mimicking cytologic features of papillary thyroid carcinoma (PTC)

Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB) specimens of thyroid nodules with varying degrees of cystic change. In some cases the histiocytic component of a cystic thyroid nodule can occur as large tissue fragments with marked nuclear atypia, including elongated nuclei with chromatin clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic cytologic features of papillary thyroid carcinoma (PTC), thus leading to diagnostic difficulty in interpretation of FNAB specimens of benign cystic thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273 cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty cases were selected due to the presence of large aggregates of histiocytic cells with the above-mentioned nuclear atypia. An immunostain for histiocytic cells using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic staining for CD68; thyroid follicular cells stained negative for CD68. We conclude that histiocytic cells in cystic goitrous nodules can show nuclear features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of value in differentiating between benign cystic thyroid nodules with histiocytic aggregates that mimic cytologic features of papillary carcinoma, and PTC with cystic change.     

Cystic papillary thyroid carcinoma in fine needle aspiration may represent a subset of the encapsulated variant in WHO classification

This study audits the reliability of ultrasound‐guided fine needle aspiration (FNA) in excluding papillary thyroid carcinoma (PTC) in thyroid cysts containing mural nodules, and investigates the histological counterpart of cystic PTC diagnosed on FNA. Using a 10–5 MHz ultrasound probe and a 27‐gauge needle, solid portions of thyroid nodules were sampled and assessed immediately using both Diff‐Quik and Ultrafast Papanicolaou stains. Unlike usual PTCs that demonstrate hypercellularity, the aspirates of cystic PTC showed low cellularity and consisted of papillae with atypical nuclei scattered in abundant thin colloid. Over a period of 13 years, histological follow‐up was obtained from 11 women and 6 men in whom cystic PTC was reported on FNA. This represented 4.4% of 383 cases of PTC reported and 0.25% of all thyroid FNAs performed. In all 17 cases, histopathology showed encapsulated PTC in various stages of cystic degeneration. Sonography correlated well with histopathology, where findings ranged from cysts with small mural nodules to solid nodules with pockets of thin colloid. In 87 patients with thyroid cysts containing mural nodules, FNA findings were benign, as was clinical follow‐up that ranged from 1 to 12 years. In conclusion, ultrasound‐guided FNA, if performed in the manner described, can reliably distinguish cystic PTC from a benign cyst with a mural nodule. Cystic PTC on FNA in this series correlates to a subset of the encapsulated variant of PTC, an entity described in the 1988 WHO Histological Typing of Thyroid Tumours in the good prognostic category. Diagn. Cytopathol. 2010;38:721–726. © 2009 Wiley‐Liss, Inc.     

A correlation study of diagnostic fine‐needle aspiration with histologic diagnosis in cystic neck lesions

The clinical diagnosis of a mass in the neck region encompasses a wide spectrum of differential diagnosis. Fine‐needle aspiration is a quick and safe technique, which can provide useful information for initial assessment and further therapeutic measures. The aim of this retrospective study was to evaluate the performance characteristics of the fine‐needle aspiration (FNA) in cystic neck lesions. Of 142 patients with FNA for cystic neck masses during 2002–2007, 92 cases were selected with a follow‐up histologic diagnosis, excluding the cystic colloid nodule of the thyroid. The cases were divided into salivary gland cystic neck (37 patients) and non‐salivary cystic neck (55 patients) mass groups. False‐positive and false‐negative diagnoses were applied only to the malignant lesions after confirmation by histopathology. In the first group, nine malignant and 28 benign diagnoses were made by FNA; of which three were false‐negative. In the second group, there were nine malignant and 46 benign diagnoses with three false negatives. The overall performance of the FNA showed 76% sensitivity and 100% specificity. In conclusion, FNA of the cystic neck lesions offers an invaluable and highly specific initial diagnostic approach for the management of the patients. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Encapsulated cystic papillary variant of medullary carcinoma of thyroid gland

Papillary variant of medullary carcinoma of the thyroid (MCT) is an unusual histologic pattern with some diagnostic difficulties. A case of encapsulated papillary variant of MCT with extensive cystic appearance is reported. A euthyroid, 43-yr-old woman with bone pain was incidentally found to have a 4.0-cm solitary, cold nodule on her left thyroid lobe. Histopathologic examination revealed an encapsulated tumor composed of a large cystic cavity with small papillary projections. The papillae were lined by multiple layers of neoplastic cells with small and regular nuclei containing condensed chromatin and lacking the characteristic “ground glass” appearance of the papillary carcinoma of the thyroid gland. Immunohistochemical studies revealed specific cytoplasmic staining of the tumor cells for calcitonin, chromogranin A, neuron-specific enolase, carcinoembryogenic antigen, and cytokeratin. Specific staining for thyroglobulin was not observed in any neoplastic cell. Staining with Congo red disclosed amyloid deposits within the stroma. The case was diagnosed as papillary variant of MCT. Medullary thyroid carcinomas may show a papillary pattern with a totally cystic gross appearance. Thyroid carcinomas should be classified according to their major immunoreactivity pattern rather than their morphologic pattern. Immunohistochemical and/or histochemical studies should be performed in all thyroid tumors that show unusual histologic features.     

“Cannonballs” and psammoma bodies: Unusual cytologic features of metastatic pulmonary small‐cell carcinoma in a pleural effusion

Large three‐dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small‐cell carcinoma occurring in an 88‐year‐old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three‐dimensional neoplastic cell aggregates (“cannonballs”), associated with rare psammoma bodies. Although the crowded three‐dimensional tumor‐cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small‐cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic “cell‐in‐cell” and “stack‐of‐coins” arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound‐guided fine‐needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small‐cell carcinoma. Metastatic pulmonary small‐cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three‐dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Sclerosing polycystic adenosis of the parotid gland: Report of one case diagnosed by fine‐needle cytology with in situ malignant transformation

Sclerosing polycystic adenosis (SPA) is a rare pathological condition affecting the salivary glands, first described by Smith etal. in 1996. Even though this lesion is being increasingly diagnosed, less than 50 cases have been published in the world literature to date. In line with numerous other pathological analogies between breast and salivary gland lesions, SPA shares with fibrocystic disease of the breast many histopathological features, i.e., fibrosis, oncocytic (apocrine) changes, hyperplasia of ductal and acinar epithelium, cystic dilation of ducts, and, often, atypical epithelial changes. Most of the described cases have followed a benign clinical course, despite the frequent possibility of atypical hyperplasia in more than 50% of the cases and of the more than occasional in situ malignant transformation. In this article, we introduce a new case occurring in the parotid gland of a 57‐year‐old male showing atypical epithelial hyperplasia and low‐grade in situ mucoepidermoid carcinoma. Fine‐needle cytology (FNC) was performed on the lesion and, when a diagnosis of SPA was prospected, the variegated cytological features of the obtained sample posed several differential diagnostic problems. The spectrum of pathological lesions entering differential diagnosis comprised sebaceous adenoma, Warthin's tumors with presence of sebaceous remnants, and low‐grade mucoepidermoid carcinoma. Histopathological examination disclosed SCA with intraductal neoplastic transformation resembling noninvasive low‐grade mucoepidermoid carcinoma. The cytological diagnosis of SPA should be entertained whenever a polymorphous picture is found on FNC samples comprising oncocytic/apocrine changes, sebaceous cells, cystic background, and epithelial hyperplasia with low‐grade cytological atypias. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Ultrasonographic thyroid findings suspicious for malignancy

Asymptomatic incidental thyroid nodules (thyroid incidentalomas) are found in up to a third of the adult population. There is notable overlap in the sonographic appearance of benign and malignant thyroid nodules. This paper provides a brief review of the ultrasound findings of thyroid nodules that are suspicious for malignancy with pathologic correlates. We then discuss the standard approach to a fine needle aspiration biopsy of a thyroid nodule at our institution. Finally, we review specific diagnostic challenges in image guided fine needle aspiration biopsies. Diagn. Cytopathol. 2013;41:1107–1114. © 2013 Wiley Periodicals, Inc.     

Isolated Langerhans cell histiocytosis of the thyroid: a report of two cases with nuclear imaging-pathologic correlation

We describe two cases of isolated langerhans cell histiocytosis (LCH) of the thyroid gland, one of which was found in conjunction with an incidental papillary carcinoma. The first case was that of a 43-year-old man who presented with a 1- to 2-cm nodule within the left lobe of the thyroid. Fine-needle aspiration cytology revealed atypical cells with convoluted nuclei in a background of eosinophils and lymphocytes. The findings prompted a recommendation for excision secondary to the high suspicion of a hematologic malignancy. Histologic sections demonstrated LCH in association with a small focus of papillary carcinoma. The second case involved a 43-year-old woman who presented with a 1.8-cm nodule within the right lobe of the thyroid. Fine-needle aspiration in this case demonstrated abundant hemosiderin-laden macrophages, occasional lymphocytes, and a single benign sheet of follicular cells. No eosinophils were seen; however, a single group of atypical histiocytic cells with cleaved nuclei was noted. The nodule was subsequently resected. Histologic examination demonstrated LCH in association with follicular nodular hyperplasia with cystic degeneration. Immunohistochemical studies were performed in both cases, revealing CD1a and S100 immunoreactivity in the Langerhans' cells. Although LCH may occur as a manifestation of systemic disease, its occurrence as an isolated finding in the thyroid is rare. Its occurrence in association with papillary carcinoma of the thyroid is even more uncommon. We present two cases of isolated LCH of the thyroid, one of which was found in association with papillary carcinoma of the thyroid. The cytologic, histologic, immunohistochemical, and radiologic features are described in each case. The ultrastructural findings from the first case are also presented.     

Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule

Serum calcitonin is a tumor marker used in the diagnosis and follow‐up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61‐year‐old female patient with known Hashimoto's thyroditis and an 8‐mm hypoechoic nodule was presented with one previously benign fine‐needle aspiration cytology (FNAC). On referral to our department, she had a moderately high‐serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high‐serum calcitonin levels. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Follicular adenoma with squamous metaplasia and cystic change: report of a case with fine needle aspiration cytological and histological features

Squamous metaplasia (SM) of thyroid follicular epithelium is known to occur in a variety of non-neoplastic lesions as well in thyroid neoplasms, notably papillary carcinoma (PC). In follicular thyroid tumors, on the other hand, SM is very rare. This case describes cytological and pathological findings in a follicular adenoma (FA) that presented as a cystic lesion with extensive SM. The fine needle aspiration (FNA) cytology sample in this case yielded only necrotic material from the cystic area and squamous cells, which being mostly of immature type, were not recognised as squamous in the cytological smears. The needle missed the solid (neoplastic) component of the lesion and on the whole the cytological picture was considered to be equivocal. FA can now be added to the spectrum of thyroid lesions that can show SM. Awareness of this will enable cytopathologists to consider non-papillary lesions in the differential diagnosis of thyroid nodules that yield squamous cells.     

Eosinophilic Replacement Infiltrates in Cystic Hashimoto’s Thyroiditis: a Potential Diagnostic Pitfall

A 50-year-old woman underwent a fine-needle aspiration biopsy for progressive enlargement of the left thyroid lobe which was cystic and solid on ultrasound exam. The smears contained innumerable eosinophilic leukocytes along with lymphocytes, Hurthle cells, cells from a papillary thyroid carcinoma (PTC), and atypical glandular and squamous cells. The cytologic interpretation was Hashimoto’s thyroiditis (HT), suspicious for epithelial neoplasm. The associated diagnostic comment stated concern for a sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) arising in a PTC. Thyroidectomy demonstrated a PTC, HT with multiple lymphoepithelial cysts, and extensive multifocal infiltrates of eosinophils, generally confined to the cyst walls. As the cytologic findings mimicked a SMECE, we report these specimens as a most unusual diagnostic pitfall.     

Cystic Medullary Thyroid Carcinoma: Report of a Case with Morphological and Clinical Correlations

Cystic lesions of the thyroid are common findings. Although many thyroid cysts are of benign, some cases of hemorrhagic degenerative changes occur in neoplastic nodules, mostly follicular neoplasms and papillary carcinomas. The occurrence of hemorrhagic changes in medullary carcinomas has never been documented with aspirative cytological and histological pictures to the best of our knowledge. A case of medullary thyroid carcinoma with a large central hemorrhagic cyst is described, and the literature regarding the pathogenesis of this regression and the occurrence of cystic neoplasms in the thyroid is reviewed.     

Significance of atypia in pancreatic and bile duct brushings: Follow‐Up analysis of the categories atypical and suspicious for malignancy

Brushing cytology is frequently utilized for the investigation of pancreatic and biliary strictures but is associated with low diagnostic sensitivity. The Papanicolaou Society of Cytopathology has presented a system for diagnostic classification which includes the categories benign, atypical, suspicious for malignancy and malignant. We studied a series of 216 pancreatic and biliary brushings with either histologic follow‐up or a minimum of 6 months clinical follow‐up to determine outcomes for the diagnostic categories (“benign,” “atypical, favor reactive,” “atypical, not otherwise specified,” “atypical, suspicious” and “malignant”). Eighty‐six of the 216 (39.8%) were designated “atypical” with 10 of these designated as “atypical favor reactive.” Forty‐five were called “atypical not otherwise specified” and 31 were interpreted as “atypical suspicious for malignancy.” On follow‐up, 2 of 10 (20%) “atypical favor reactive” were eventually associated with a malignant diagnosis and 23 of 31 (74.2%) “atypical, suspicious for malignancy” demonstrated a malignant outcome. The remaining 45 brushings in the “atypical” category were “atypical not otherwise specified,” and 62% of these were associated with malignancy on follow‐up. Stratification of the “atypical” category into “atypical favor reactive,” “atypical, not otherwise specified” and “atypical, suspicious for malignancy” improves diagnostic accuracy. The “atypical suspicious for malignancy” category has a follow‐up similar to the “malignant” category while the “atypical favor reactive” category is associated with a clinical outcome similar to that of the “benign” category. Diagn. Cytopathol. 2014;42:285–291. © 2013 Wiley Periodicals, Inc.     

A diagnostic pitfall: nodular tumor-like squamous metaplasia with Hashimoto's thyroiditis mimicking a sclerosing mucoepidermoid carcinoma with eosinophilia

Nodular tumor-like squamous metaplasia with Hashimoto's thyroiditis is an exceptional, benign condition presenting diagnostic difficulties for the pathologist. The main differential diagnosis is a sclerosing mucoepidermoid carcinoma (SMC) with eosinophilia. One case arising in a 50-year-old Caucasian man is reported. Histologically, the nodule consisted of large nests of squamous cells surrounded by connective tissue in Hashimoto's thyroiditis. We present the different histological criteria, allowing us to eliminate an SMC and other neoplastic tumors of the thyroid. The etiology of this tumor-like lesion, which is still under debate, is discussed.     

The “drunken honeycomb” feature of pulmonary mucinous adenocarcinoma: A diagnostic pitfall of bronchial brushing cytology

Pulmonary mucinous adenocarcinoma (PMA) is the terminology recently proposed in the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) International Multidisciplinary Classification of Lung Adenocarcinoma Guidelines for most tumors previously classified as mucinous bronchioloalveolar carcinomas (mBACs). PMA is histologically characterized by lepidic growth and at least some degree of invasive growth of goblet or columnar neoplastic cells with abundant intracytoplasmic mucin. We report here the cytologic features of PMA in a bronchial brushing specimen. The patient is an 84‐year‐old woman with a persistent dense consolidation in the right middle lobe of the lung found on non‐contrast computed tomography (CT) scan. Bronchial brushing smears showed a monotonous population of columnar neoplastic cells forming “drunken honeycomb”‐like cell clusters. The neoplastic cells displayed inconspicuous cytologic atypia. The concurrent transbronchial tissue biopsy and the resection specimen confirmed the diagnosis of PMA. Due to the bland nuclear features, the neoplastic cells in the bronchial brushing specimen were interpreted as benign at the time of the initial diagnosis, demonstrating a diagnostic pitfall of bronchial brushing cytology. A high index of suspicion is recommended when a lung lesion with “drunken honeycomb”‐like cell clusters is encountered in bronchial brushing specimens. The review of the literature regarding the recently designated PMA is presented. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.