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Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that usually behaves aggressively. After resection, serological surveillance for calcitonin and carcinoembryonic antigen (CEA) is used to prompt a radiographic search for metastatic disease. We report a case of a 65-year-old woman who presented with a large liver metastasis 37 years after she underwent thyroidectomy for organ-confined MTC. Her clinical course over that time showed a smoldering pattern in which she was symptom free until presentation even though her serum calcitonin and CEA concentrations were elevated for 17 years, and a small equivocal radiographic lesion in the liver was detected 10 years prior to presentation. Cytopathology from an ultrasound guided fine needle aspiration of the hepatic lesion was diagnostic for metastatic MTC. This case highlights the ability for smoldering residual MTC to suddenly transform to aggressive biological behavior after a long period of clinical remission. Diagn. Cytopathol. 2015;43:45–48. © 2014 Wiley Periodicals, Inc.

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.

BACKGROUND Pineal gland lesions are rare, with only a few cytologic descriptions occurring in the literature, according to the authors' knowledge. The current article describes the cytopathologic characteristics of 20 such lesions with discussion of differential diagnoses. METHODS Cytologic material was obtained either by fine-needle aspiration biopsy (FNAB) under stearotactic radiologic guidance or by touch imprinting (TI) at the time of frozen sectioning. The 20 specimens include pineoblastoma (five specimens), pineocytoma (four specimens), astrocytoma (three specimens), germ cell tumor (three specimens), meningioma (one specimen), epidermoid cyst (three specimens), and pineal cyst (one specimen). Smears were stained with Diff-Quik and with Papanicolaou and hematoxylin and eosin stains. In selected specimens, immunoperoxidase (IPOX) stains were performed on cell block sections using synaptophysin, neuron-specific enolase, placental alkaline phosphatase, glial fibrillary acidic protein, leukocyte common antigen, cytokeratins, and human chorionic gonadotropin antibodies. RESULTS Several cytomorphologic characteristics unique to each lesional category with occasional overlapping features were observed. The unique features included the following: small, hyperchromatic, round to oval cells with frequent rosetting (pineocytoma), with a few specimens in addition showing hypercellularity, crowding, mitoses, and necrosis (pineoblastoma); pleomorphic round cells in a fibrillary background (astrocytoma); large polygonal cells with prominent nucleoli and clear cytoplasm (germ cell tumor); spindled fibroblastic cells (meningioma); anucleate squames and mature squamous cells (epidermoid cyst); and small uniform polygonal cells (pineal cyst). When necessary, IPOX studies supported the morphologic diagnoses. CONCLUSIONS FNAB and TI cytology were found to provide a rapid and reliable diagnosis of pineal lesions. This is particularly important when dealing with minute amounts of tissue material. Both techniques appeared to provide equally good cytomorphology on smears. IPOX studies played an important complementary role in difficult cases when performed on cell blocks. Cancer (Cancer Cytopathol) 2005. © 2005 American Cancer Society.

Although cancers metastatic to the thyroid are frequently mentioned in autopsy studies, such a finding is quite rare in routine clinical practice. Metastatic non-small-cell carcinomas to the thyroid may present a diagnostic dilemma, particularly when they share morphological similarities with primary thyroid tumors. Herein, we report a case of metastatic bronchioloalveolar carcinoma that presented as an isolated left thyroid nodule in a 68-year-old woman. The aspirates were cellular and showed numerous papillary-like tissue fragments, elongated nuclei with prominent nuclear grooves, frequent mitoses, and psammoma bodies. The latter features raised the possibility of papillary thyroid carcinoma. However, also seen were three-dimensional tumor nests and acinar-forming fragments. Immunostains (positive for cytokeratin-7 and carcinoembryonic antigen and negative for cytokeratin-20 and thyroglobulin) confirmed the metastatic nature of the carcinoma. In a patient with known primary neoplasm, the differential diagnosis of a thyroid nodule should always include a metastatic lesion along with primary neoplasia.

Stereotactic brain fine-needle aspiration (FNA) is a valuable diagnostic modality for evaluating space-occupying central nervous system disorders. Colloid cyst (CC) is a rare nonneoplastic lesion thought to arise from misplaced endodermal tissue in the anterosuperior portion of the third ventricle. This study summarizes cytomorphologic features of CC on FNA along with clinical, radiologic, and histopathologic correlation. Ten cases of CC of the third ventricle diagnosed on FNA were retrospectively reviewed for a period of 12 yr (1989–2000). Material was obtained under stereotactic radiologic guidance. Smears were stained with Diff-Quik and Papanicolaou stains and cell block sections with hematoxylin and eosin. The aspirates showed a characteristic sticky and viscous quality on gross examination. Smears showed abundant, amorphous, proteinaceous material with staining qualities similar to colloid aspirated from thyroid. This included a purplish, filmlike coating of the slide with occasional “cracking” artifact; thick, globular, eosinophilic fragments; and granular, ropelike, and somewhat viscous, mucinous material. Pathognomonic radiating hyphae-like structures were not seen. The cellular components varied from isolated cuboidal/columnar cells to large tissue fragments of glandular-type epithelium with focal ciliated border. Goblet cells were frequently identifiable, as were fragments of collagenous cyst wall. Stereotactic FNA of the CC of the third ventricle is an accurate and cost-effective diagnostic modality. Cytomorphology coupled with the radiologic features is sufficiently unique for the diagnosis of this rare pathologic entity. Diagn. Cytopathol. 2002;27:27–31. © 2002 Wiley-Liss, Inc.

The accuracy of using a combination of cytopathologic and histopathologic techniques to diagnose stereotactically guided brain biopsies was investigated in 74 patients. Diagnostic accuracy was assessed by determining whether classification of the biopsies as gliosis, astrocytoma (A), anaplastic astrocytoma (AA), or glioblastoma multiforme (GBM) predicted survival. The utility of on-site evaluation using Diff-Quik-stained crush preparations was also assessed. The patients ranged in age from 5 to 88 years (mean, 55 years) and were followed for over 2 years in most cases. Four cases (5%) were classified as gliosis (G), 7 (9%) as atypical gliosis (AG), 4 (5%) as high-grade mixed oligodendroglioma/ astrocytoma (OA), 11 (15%) as astrocytoma (A), 21 (28%) as anaplastic astrocytoma (AA), and 27 (36%) as glioblastoma multiforme (GBM). Median survival was 11 months in patient with OA, 57 months in patients with A, 10 months in patients with AA, and 5 months in patients with GBM. Diagnosis of Diff-Quik-stained crush preparations made during the biopsy procedure was highly correlated with the final diagnosis and survival. We conclude that the diagnosis of stereotactic brain biopsies using cytopathology with on-site evaluation in combination with histopathological evaluation of needle cores is accurate based on a survival analysis. However, A and G may be difficult to distinguish.

Pulmonary sequestration is defined as a congenital malformation of abnormal lung tissue that does not communicate with the airway system and that receives blood supply from anomalous arteries. The majority of these sequestrations are encountered in the pediatric population. Surgical excision is the treatment of choice, with excellent prognosis. We studied a case of an extralobar pulmonary sequestration in a young adult, presenting as an intrathoracic mass; it was aspirated twice, final diagnosis being rendered after surgical resection. The cytologic findings and the accompanying diagnostic difficulties to our knowledge have never been reported.

The Fuhrman grading system of renal cell carcinoma (RCC) consists of four grades based on nuclear size/contour and nucleolar conspicuousness. Fuhrman grading of histpathologic material is an independent prognostic parameter for RCC. Although widely used in surgical pathology, Fuhrman grading is not routinely performed on cytologic material. Thirty-three cases of renal fine needle aspirations (FNAs) with histologically proven RCC were retrieved from the cytopathology archives at Johns Hopkins Hospital. Fuhrman grade was determined independently and blindly by three faculty cytopathologists and compared with the Fuhrman grade of the subsequent surgical pathology specimen. The 33 resection specimens had the following Fuhrman grades: 0/33, grade I; 24/33 (73%), grade II; 9/33 (27%), grade III; and 0/33, grade IV. After Fuhrman grading was applied to the FNA material, diagnostic sensitivity was 83% for grade II versus 44% for grade III. The specificity and accuracy were 50 and 75%, respectively, for grade II versus 100% and 84% for grade III. Diagnostic sensitivity for grade II tumors ranged from 38 to 83%, grade III 44-62%. Diagnostic specificity for grade II tumors ranged from 50 to 78%, grade III 80-100%. Accuracy ranged from 48 to 75% for grade II and 75-87% for grade III. Using a two-tier grading model, accuracy improved to 84.2%. In our experience, Fuhrman grading of FNA specimens yielded variable results. There was only moderate agreement between cytopathologists, with an overall tendency to undergrade the tumor when compared with the resection specimen. Averaging the participants' grading and using a two-tier instead of four-tier system improved overall performance.

Fine-needle aspiration of the prostate has failed to gain widespread acceptance among pathologists more familiar with histologic sections. The authors aspirated 27 freshly excised radical prostatectomy specimens with needles of varying caliber and type and found a 22-gauge Turner needle (Cook Incorporated, Bloomington, IN) which obtained large tissue fragments suitable for cell block preparation as well as high quality cytologic specimens. Thirty men with prostate nodules each had 14-gauge transperineal core biopsy and fine-needle aspiration. In 20 cases, cytologic smears and cell blocks and core biopsies agreed on a diagnosis: 12 benign and eight carcinoma. Of seven cases that were atypical by cytologic smears, five were benign on cell block and core; one was benign on cell block and carcinoma on core; and one was carcinoma on cell block and core. Three cases with scant specimens and diagnoses of carcinoma by cytologic smears were benign on cell blocks and cores: one contained seminal vesicle on review; one had repeat benign biopsies; and one had three microscopic foci of low-grade carcinoma in his radical prostatectomy specimen. This fine-needle aspiration technique provides histologic sections which are especially useful to those gaining experience with cytologic specimens of the prostate. Cases with discordant diagnoses on cell block and cytologic preparations warrant further evaluation.

Tumoral calcium pyrophosphate dihydrate deposition disease (CPPD) is a rare non-neoplastic entity which mimics primary or metastatic soft-tissue or skeletal malignancy. Fewer than a dozen cases have been reported in the literature with only histologic descriptions. We present cytologic findings of a unique case of CPPD in a 73-year-old black female with a history of end-stage renal disease. A fine-needle aspiration (FNA) was done on a 4 x 4-cm neck mass which was clinically thought to be malignant. Cytopathologic examination showed numerous macrophages with markedly distended cytoplasm and containing multiple yellowish-orange, short rhomboid crystals. These were strongly birefringent on polarized microscopy, consistent with CPPD crystals.

The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus in not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously.

Early bronchogenic carcinoma detected by sputum cytology frequently cannot be localized by conventional bronchoscopic techniques. Six occult tumors were localized in this study with new techniques in differential cytology and flexible fiberoptic equipment. A three-phase study is carried out including: 1. Cytologic localization, 2. Fiberoptic survey, and 3. Histologic mapping of bronchial margins. Findings are recorded by means of a color television documentation system. A review of the surgical pathology in our four cases has revealed a relatively large area of in-situ carcinoma in the region of very small invasive tumors.

Lung cancer is rarely diagnosed and treated while still localized. Sputum cytology allows detection of radiologically occult tumors but conventional endoscopic procedures frequently prove inadequate for localization. It is the purpose of this report to outline the endoscopic observations and methods we have developed in successfully localizing 17 consecutive, radiologically occult carcinomas discovered in the sputum of 15 patients. A detailed examination of the upper respiratory tract demonstrated occult tumors in two patients. A segment by segment fiberbronchoscopic study under anesthesia allows multiple brushings and meticulous handling of specimens. Lesion localization is provided as well as identification of synchronous second primary tumors. Biopsies at the lobar spur and carina assist in determining the proximal extent of carcinoma in situ at potential surgical margins. Newer methods should enhance our recognition of inapparent carcinoma in situ allowing more efficient and more accurate tumor localization and a better appreciation of its extent.