Intranuclear Cytoplasmic Inclusions Research Articles

Hepatocellular carcinoma presenting as a chest wall mass - An unusual case diagnosed on cytology with review of literature.

Hepatocellular carcinoma (HCC) is associated with an aggressive behavior and a strong tendency for extrahepatic metastasis. Although 5%-15% patients have metastases at diagnosis, presentation with symptoms exclusively related to extrahepatic metastases is rare. An 82-year-old male presented with an isolated left anterolateral chest wall swelling. Ultrasonography revealed a soft tissue mass involving the anterior chest wall with adjacent rib erosion. Serum protein electrophoresis showed increase in beta-2 region. A clinical diagnosis of multiple myeloma was considered. Fine needle aspiration cytology from the swelling showed loosely cohesive clusters of polygonal cells with traversing blood vessels. Cells showed abundant vacuolated to granular cytoplasm, round nuclei with frequent intranuclear cytoplasmic inclusions. A differential of metastatic HCC and renal cell carcinoma was considered. Subsequent imaging showed a 12 cm mass in the liver. Biopsy from chest wall mass with immunohistochemistry confirmed the diagnosis. Lungs and lymph nodes are the commonest sites for metastatic HCC; presentation as chest wall metastasis is rarely reported. The classical cytomorphology of HCC proved useful in diagnosing metastasis at a rare site. Recent studies have shown that beta-2-globulin is a promising biomarker for early diagnosis of HCC in patients with chronic liver disease.

Three-dimensional structural analysis of papillary thyroid carcinoma nuclei with serial block-face scanning electron microscopy (SBF-SEM).

Nuclear morphology of carcinoma cells is critical for the pathological diagnosis of papillary thyroid carcinoma (PTC). However, three-dimensional architecture of PTC nuclei is still elusive. In this study, we analyzed the three-dimensional ultrastructure of PTC nuclei using serial block-face scanning electron microscopy which takes advantage of the high-throughput acquisition of serial electron microscopic images and three-dimensional reconstruction of subcellular structures. En bloc-stained and resin-embedded specimens were prepared from surgically removed PTCs and normal thyroid tissues. We acquired two-dimensional images from serial block-face scanning electron microscopy and reconstructed three-dimensional nuclear structures. Quantitative comparisons showed that the nuclei of carcinoma cells were larger and more complex than those of normal follicular cells. The three-dimensional reconstruction of carcinoma nuclei divided intranuclear cytoplasmic inclusions into "open intranuclear cytoplasmic inclusions" connecting to cytoplasm outside the nucleus and "closed intranuclear cytoplasmic inclusions" without that connection. Cytoplasm with abundant organelles was observed in open inclusions, but closed inclusions contained fewer organelles with or without degeneration. Granules with a dense core were only observed in closed inclusions. Our observations suggested that open inclusions originate from nuclear invaginations, and disconnection from cytoplasm leads to closed inclusions.

Cytologic Findings in Serous Effusion Specimens from Melanoma Patients

Introduction: Metastatic melanoma (MM) is an uncommon finding in serous effusion specimens with a highly variable cytomorphology. Methods: We reviewed specimens submitted over a 19-year period to determine (a) the range of cytologic findings in effusion specimens from melanoma patients and (b) the cytologic presentation and immunoprofile of MM in effusion specimens. Results: Of 123 serous effusion specimens from patients with clinical notes of melanoma, 59% were reported negative for malignancy, 16% were reported with a non-melanoma malignancy, 19% MM, and 6% atypical, MM not excluded. Pleural fluids were twice as likely to be reported as MM than peritoneal samples. Review of 44 cases with confirmed MM showed the most common cytologic pattern was epithelioid. Most (88%) cases contained mainly dispersed plasmacytoid cells, but many (61%) also contained malignant cells arranged in loose groups. Rare cases also had spindle cells, giant bizarre cells, small lymphoid-like cells, or cells with large hard-edged vacuoles, mimicking other metastatic malignancies. MM cases containing predominantly plasmacytoid cells often mimicked reactive mesothelial cells. As well as being composed of cells of similar size, features such as bi- and multinucleation, round nuclei, mild anisokaryosis, nucleoli, and loose groups were common to both. Features seen more commonly in MM than reactive cells included large nucleoli (95%) and intranuclear cytoplasmic inclusions (41%), binucleate “bug-eyed demons,” and small punctate vacuoles on the air-dried preparations. Pigment was identified in 36% of cases. Immunohistochemistry (IHC) is a valuable aid in confirming the cell type. The sensitivity for the most commonly used melanoma markers was as follows: S100 84% (21/25), pan-melanoma 100% (19/19), HMB45 92% (11/12), Melan A 92% (11/12), SOX10 91% (10/11). No staining was reported for calretinin (0/21), AE1/AE3 (0/11), EMA (0/16), Ber-Ep4 (0/13). Discussion: Effusion specimens from patients with a history of melanoma are frequently (40%) malignant but almost as likely to be reported as a nonmelanoma malignancy as MM. The cytology of MM may mimic a wide range of other metastatic malignancies but also often closely resembles reactive mesothelial cells. It is important to be aware of this latter pattern so that IHC markers can be applied.

Cytopathology of the distant metastasis of papillary carcinoma of thyroid.

To describe the cytomorphological features at distant metastatic sites apart from lymph nodes in papillary thyroid carcinoma (PTC). A total of eight cytology cases from seven patients reported as metastatic papillary carcinoma of thyroid were reviewed including available clinical and radiological details. The details clinical and cytological features were studied. There were a total of five males and two female patients. Two of these patients presented with lung nodules, two patients had bony lesion and lesion in kidney respectively and one patient had both bony and soft tissue lesions. Pleural fluid and bronchoalveolar lavage were received from remaining two patients. Cytology smears revealed papillary clusters and sheets of tumor cells, having round to oval nuclei with pale powdery chromatin, inconspicuous nucleoli and scant to moderate amount of cytoplasm. Nuclear features such as longitudinal nuclear grooves, intranuclear cytoplasmic inclusions were seen in all but one case. Nuclear enlargement and overlapping were variably present. The diagnosis of metastatic PTC at uncommon locations is difficult. Since many of these locations are amenable to fine needle aspiration or exfoliative cytology evaluation, clinical awareness, and identification of classic cytomorphologic features can offer quick and accurate diagnoses. In cases with occult or unknown PTC presenting with metastases, cytomorphology may help in the prompt suggestion of detecting primary tumor in the thyroid.

Computer-assisted image analysis of cytological specimens clarify the correlation between nuclear size and intranuclear cytoplasmic inclusions regardless of BRAFV600E mutation in papillary thyroid carcinoma.

The morphological features of nuclei in cytological and histological specimens were compared and examined for the presence of BRAFV600E mutation and the appearance rate of intranuclear cytoplasmic inclusions (NI). BRAFV600E mutation was identified using a mutation-specific antibody (clone; VE1) in 103 thyroid papillary carcinoma cases at Gunma University Hospital. The nuclear area, perimeter, and roundness of the corresponding cytological specimens and haematoxylin and eosin-stained specimens were analysed using image analysis software, and the appearance rate of NI was calculated and compared. BRAFV600E mutation was detected in 71 (69%) cases. The appearance rate of NI was significantly higher in the BRAFV600E mutation-positive group in cytological and histological specimens (P=.0070 and .0184, respectively). Significant differences were observed between the BRAFV600E mutation-negative and -positive groups in the average nuclear area and average nuclear perimeter in cytological specimens (P=.0137 and .0152, respectively). In addition, nuclear enlargement was correlated with the appearance rate of NI regardless of the presence of BRAFV600E mutation in cytological specimens. In the BRAFV600E mutation-negative group, the nuclear area and perimeter were significantly smaller in the lymph node metastasis-positive cases (P=.0182 and .0260, respectively). This study found that the appearance rate of NI was positively correlated with the nuclear area and perimeter and negatively correlated with nuclear roundness in cytological specimens. Furthermore, these results were observed regardless of the existence of BRAFV600E mutation. These results have never been previously reported and clearly demonstrate the usefulness of cytological specimens in computer-assisted image analysis.

Diagnosis and management of hyalinizing trabecular tumor of the thyroid: a single-institution experience.

Hyalinizing trabecular tumor (HTT) of the thyroid is a mostly benign disease. Its cytological and pathological diagnosis is often difficult, because HTT cells and papillary thyroid carcinoma (PTC) cells share similar features (e.g., intranuclear cytoplasmic inclusions and nuclear grooves). At our institution, 38 patients were diagnosed as or highly suspected of having HTT without the possibility of PTC, based on cytology: 19 of these patients underwent immediate surgery (surgery group) and the remaining 19 underwent active surveillance without surgery (AS group). The surgery-group patients' tumor sizes were significantly larger (p < 0.0001) than those in the AS group. During AS (median 38 months), only one patient (5%) showed tumor enlargement by ≥3 mm; the AS was continued. Of the 34 patients pathologically diagnosed with HTT, 22 (65%) were cytologically diagnosed or highly suspected as having HTT without the possibility of PTC. Of the nine patients who were suspected to have HTT but PTC was possible and surgery was performed, two (22%) and seven (78%) were pathologically diagnosed as having PTC and HTT, respectively. Five patients were cytologically diagnosed with PTC, but pathologically diagnosed as having HTT. No patients showed HTT recurrence during postoperative follow-up (median 60 months). These findings suggest that (1) active surveillance can be a valid strategy for managing tumors that are cytologically diagnosed as HTT with no possibility of PTC; (2) surgery is recommended for tumors suspected of being HTT but may be PTC, and (3) the prognosis of HTT in both the AS and surgery groups was excellent.

Value of Combined Cytomorphological Parameters in Improving Diagnostic Accuracy of Papillary Thyroid Carcinoma on Cytology - The Five Dependable Features.

Background:Fine-needle aspiration cytology remains the preliminary test for diagnosing papillary thyroid carcinoma (PTC). Numerous features are established to arrive at the diagnosis. However, few cases pose a challenge to correctly diagnose PTC. Our study aims to elicit the combination of features to aid in the diagnosis of such cases.Materials and Methods:Cytology smears of histologically proven cases of PTC and benign diagnoses were included as case (n = 36) and control group (n = 38), respectively. Features including papillae with cores, 3-D caps, nuclear grooves (NG), intranuclear cytoplasmic inclusions (INCI), giant cells, macrophages, cellular swirls, psammoma bodies, pale chromatin, nuclear overlapping, nuclear enlargement, and metaplastic cells were assessed. Statistic tests including Independent t test/Mann–Whitney Test and Chi-Square test/Fisher's Exact test were used. Receiver operating characteristic curve was used to assess the cut-off point of many cytological features to predict PTC. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cytological features was calculated to predict PTC.Results:Presence of five or more cytological features (papillae with cores, cellular swirls, NG, INCI, and psammoma bodies) together could diagnose PTC (PPV) in 78.95% of the cases, with a NPV of 83.33%. Diagnostic accuracy of these five features combined was 81.08%. Papillae with cores and nuclear grooving were the most sensitive cytological features, whereas INCI followed by cellular swirls and NG were the most specific features.Conclusion:Relying on a combination of the most sensitive and specific features rather than any one cytological feature can help reduce the misdiagnoses in PTC.

Study of various nuclear features of papillary thyroid carcinoma in other thyroid lesions

Introduction: Papillary thyroid carcinoma is the only thyroid malignancy that is diagnosed on the basis of its nuclear characteristics, regardless of cytoplasmic features, growth patterns or immunohistochemistry. Although nuclear features have become hallmark for the diagnosis, they are neither constant nor specific. They can be seen in other tumours and non-tumours condition of thyroid. With the aim to know the frequency of various nuclear features of papillary thyroid carcinoma in other thyroid lesions and also to find out which of the various nuclear features are most diagnostic of papillary thyroid carcinoma, this study was done. Materials and Methods: The present study was conducted on Fine needle aspiration cytology of thyroid lesions where corresponding histopathological diagnosis was available, from 2010 to 2016. All cytology smears of were reviewed by two investigators who were blinded with respect to the final histopathological diagnosis. Results: 155 cases were included in the study; category 2 was the most common constituting 76%, followed by category 6 which was 35%. Frequency of various nuclear features of papillary carcinoma in other thyroid categories varied from 10% to 33%. Conclusion: Frequency of various nuclear features of papillary carcinoma in other thyroid categories varied from 10% to 33% and Intranuclear cytoplasmic inclusions are the most diagnostic nuclear features of papillary carcinoma. Keywords: Papillary thyroid carcinoma, Nuclear inclusions, Nuclear grooves, Fine granular chromatin.

Diagnostic significance of various cytomorphological features and their quantification for the diagnosis of papillary carcinoma thyroid on fine needle aspiration cytology

Introduction: The relative reliability of the morphological features for making a diagnosis of PTC when considered independently is debatable. Quantification of morphological features has been attempted to improve the diagnostic efficacy of FNA thyroid, but universal acceptance is lacking. Aim: This study was aimed to analyze the independent diagnostic significance of the four common morphological features-Nuclear grooves (NG), Intra-nuclear cytoplasmic inclusions (INCI), Papillary Fragments and Metaplastic Cytoplasm, in thyroid swellings using a quantitative approach. Materials and Methods: Retrospective study including thyroid FNA cases with corresponding histopathological report was analyzed. Eighty six cases had at least one of the four morphological features mentioned. The cases with NG were categorized into three groups: >/= 20%; 10-19% and Results: The sensitivity, specificity, PPV and NPV of NG for PTC in the category of ? 20% was 53.3%, 98.2%, 94.1% and 79.7% respectively and the same in the category of > 10% were 66.7%, 75%, 58.8% and 80.8% respectively. Specificity and sensitivity of ‘Frequent’ INCI were 100% and 36.67% respectively. Conclusion: Typical morphological features of PTC can be seen in non-malignant conditions as well. Occurrence of NG >20% and INCI >5% are highly specific for the diagnosis of PTC. Cases with NG between 10-19% should be considered as ‘suspicious for malignancy’ and pathologist should cautiously look for other morphological features. Keywords: Papillary carcinoma thyroid (PTC), FNAC, Cytology, Morphology, Quantification.

Acceleration of BRAFV600E-induced thyroid carcinogenesis by TGFβ signal deficiency in mice.

Transforming growth factor-β (TGFβ) has pleiotropic actions, including both anti- and pro-tumorigenic abilities. We have previously shown no tumor development in the thyroid-specific TGFβ receptor type II knockout (Tgfβr2 KO) mice, indicating the insufficiency of defective TGFβ signal itself for thyroid cancer initiation. In the current study, we evaluated whether defective TGFβ signal accelerates BRAFV600E-mediated thyroid carcinogenesis in our mouse model, in which intrathyroidal injection of adenovirus expressing Cre under thyroglobulin (TG) promoter (Ad-TgP-Cre) into thyroid lobes of conditional BrafV600E knock-in mice (BrafCA) induces thyroid cancers 12 months later. BrafCA/wt;Tgfbr2floxE2/floxE2 mice were generated by crossing Tgfbr2floxE2/floxE2 and BrafCA mice, and Ad-TgP-Cre was injected into the left lobes of 4-6-week-old mice. Mice were sacrificed at 6 and 12 months, and the thyroid tissues were subjected to H&E and immune-histochemistry and -fluorecence. Thyroid tumors were observed in 8 of 10 mice at 6 months and 4 of 7 mice at 12 months. These tumors were judged to be malignant by H&E staining, because of the presence of papillary growth of atypical follicular cells, intranuclear cytoplasmic inclusions and so on. Immunohistochemical analyses using thyroid cancer tissues obtained at 6 months demonstrated variable levels of TG but steady levels of Paired Box-8 expression and higher Ki67 positivity. The degree of epithelial-to-mesenchymal transition could not be evaluated because normal thyroid tissues and thyroid cancers developed in BrafCA and BrafCA/wt;Tgfbr2floxE2/floxE2 mice were all E-cadherin+/vimentin-, that is, epithelial type. In a mouse model, defective TGFβ signaling pathway accelerates BRAFV600E-induced thyroid cancer development, which is occasionally accompanied by reduced TG expression implying dedifferentiation. The former finding is consistent with anti-tumorigenic ability of TGFβ in early tumorigenic process, but the latter is contradictory to generally accepted concept for TGFβ-induction of dedifferentiation.

A case of paraganglioma of the retroperitoneum with intranuclear cytoplasmic inclusions in the giant tumor cells

A case of paraganglioma of the retroperitoneum with intranuclear cytoplasmic inclusions in the giant tumor cells

LUNG NODULE WITH PAPILLARY FEATURES ON BIOPSY: A DIAGNOSTIC DILEMMA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Papillary adenocarcinoma (PA) is a rare sub type of adenocarcinoma of the lung. It can have histological and immunohistochemistry features like papillary thyroid carcinoma (PTC). We report a case of lung nodule found to have features suggestive of PTC on biopsy. CASE PRESENTATION: A 69-year-old female with a history of COPD and colon cancer presented to the pulmonologist for follow up of a solitary lung nodule in the right upper lobe, which was first diagnosed two years back. It had shown a recent increase in size from 8 mm to 12 mm, with spiculated pattern on imaging. Biopsy of the lung nodule was highly suspicious for PTC, with positive TTF1, papillary features, intranuclear cytoplasmic inclusions, nuclear grooves, negative CK20, CDX2 immunostain. She denied any symptoms of hypo/hyperthyroidism, weight loss, fatigue, cough, dyspnea, neck radiation exposure. She had a 37.5 pack-year smoking history. Family history was non-contributory. Vital signs and physical examination were unremarkable. Thyroid function tests including TSH, fT3, fT4 were within normal limits. With findings suggestive of PTC on biopsy, initial concern was for metastatic disease. Thyroid ultrasound showed 0.7cm cystic nodule in the right lobe, and two solid nodules of 0.9cm, 0.8cm on the left. FNAC of the nodules showed benign pathology. Tumour board was consulted, and they recommended MRI of the neck with contrast which revealed mildly enlarged thyroid with sub centimetric nodules, without lymphadenopathy, making our suspicion for metastatic PTC very low. Ectopic thyroid tissue carcinoma, PA of the lung were now being considered as differentials. Lung biopsy slides were sent to Mayo clinic for a second opinion, which revealed neoplastic cells with lining of papillary structures, with positive immunochemistry for napsin-A and TTF1, and negative for Pax-8, confirming the diagnosis of primary PA. DISCUSSION: PA accounts for 7-12% of lung adenocarcinomas, with a predilection for female smokers. It mimics PTC, as they can have similar histological features of pseudo-inclusions, intra-nuclear grooves. In such cases, immunohistochemistry aids in the diagnosis. Although, our patient had a nodule which morphologically resembled PTC, the history of solitary lung nodule, in the absence of significant findings on imaging and biopsy made the diagnosis of PTC unlikely. CONCLUSIONS: Most common etiology for lung nodule showing papillary features is metastatic disease. The combination of positive TTF1, napsin-A, and negative Pax-8 is a reliable tool to differentiate primary lung adenocarcinoma from metastatic tumors. Understanding the existence of papillary thyroid carcinoma-like primary pulmonary papillary adenocarcinoma will avoid misdiagnosis or unnecessary investigations. Reference #1: Zhu YZ, Li WP, Wang ZY, Yang HF, He QL, Zhu HG, Zheng GJ. Primary pulmonary adenocarcinoma mimicking papillary thyroid carcinoma. J Cardiothoracic Surg. 2013; 17; 8:131 Reference #2: El-Maqsoud NM, Tawfiek ER, Abdelmeged A, Rahman MF, Moustafa AA. The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in differentiating between primary and metastatic lung carcinomas. Tumour Biol. 2016; 37(3):3123-34 Reference #3: Karmakar S, Nath A, Neyaz Z, Agarwal V, Ahsan S. Primary papillary adenocarcinoma of lung: Report of two cases. Lung India. 2017; 34(3):299-302 DISCLOSURES: No relevant relationships by Shujaa Faryad, source=Web Response No relevant relationships by Pallavi Pradeep, source=Web Response

Important cytological findings for distinction between follicular variant and conventional papillary thyroid carcinoma, including noninvasive follicular thyroid tumors with papillary-like nuclear features.

We studied cytological specimens of conventional papillary thyroid carcinoma (PTC), follicular variant papillary thyroid carcinoma (FVPTC), and noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) (formerly noninvasive FVPTC) to identify useful cytological parameters for their differentiation. Cytological findings of invasive FVPTC and NIFTP were very similar to each other but differed from those of conventional PTC. Intranuclear cytoplasmic inclusions, true papillary cell clusters, monolayered cell sheets, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background were the observed characteristic features of conventional PTC. Microfollicular cell clusters and dense globules of colloids were characteristic features of invasive FVPTC and NIFTP. Scoring the eight parameters (intranuclear cytoplasmic inclusions, nuclear grooves, powdery chromatin, true papillary cell clusters, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background) readily distinguished NIFTP from conventional PTC, but could not distinguish NIFTP from invasive FVPTC. The average total score of NIFTP, invasive FVPTC, and conventional PTC were 2.60 ± 0.55, 2.63 ± 0.62, and 4.57 ± 0.99, respectively. The difference between conventional PTC and NIFTP or invasive FVPTC was statistically significant (p < 0.001, Student's t-test). Individuals with more than three of the identified parameters likely harbor conventional PTC, rather than NIFTP. In this way, 87.5% (112/128) of conventional PTCs could be differentiated from NIFTP, and definitively diagnosed as malignant by cytology.

Functional State of Cells During their Life and on their Journey Toward Inactivity and Death: Search for Morphological Evidence in Thyroid Fine Needle Aspiration Smears.

Synthesis and storage of thyroglobulin as well as synthesis of thyroid hormones and their release into the circulation are important functions of thyroid, which were studied in fine needle aspiration (FNA) smears from thyroid lesions. Evidence of thyroglobulin synthesis was demonstrated in neoplastic and nonneoplastic follicular cells, especially in Hürthle cells, in the form of colloid inclusions. Whereas the pinocytic vesicles containing colloid at the luminal end of in nonneoplastic and neoplastic follicular cells indicated engulfment of colloid for synthesis of thyroid hormones (T3 and T4), the marginal vacuoles (MVs) (fire-flare appearance) at the basal aspects of follicular cells suggested their release on way to the interfollicular capillaries. The morphological evidence of secretary activity could also be demonstrated in medullary thyroid carcinoma (MTC) in the form of azurophilic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions; the secretory material, likely to be amyloid, present in MTC cells, and their release to the extracellular space was confirmed by positive immunocytochemical staining for calcitonin. It was found that nuclear grooves and related intranuclear cytoplasmic inclusions (INCIs) in papillary thyroid carcinoma (PTC) possibly represent an initial step of a degenerative process leading to formation of inactive cerebriform nuclei. Based on observation regarding formation and release of precursor substances for psammoma bodies (PBs), it was also suggested that PBs may not represent a process of dystrophic calcification over infarcted/dead papillae but suggest an active biological process, which leads to inhibition of growth of neoplastic cells and acts as a barrier against spread of PTC.

Thyrolipomatosis: A case report with review of the literature.

Fatty tissue is not usually present within the thyroid gland. Only a few fat-containing thyroid lesions have been reported to date, and thyrolipoma is the most common fat-containing lesion of the thyroid gland. Thyrolipomatosis is a condition characterized by diffuse mature adipose cell infiltration of the normal thyroid gland. In this report, we describe what is, to the best of our knowledge, the 12th documented case of thyrolipomatosis, and review the fat-containing lesions of the thyroid gland. A 68-year-old Japanese woman presented with a neck mass that had first been noticed ~7 years earlier. A computed tomography scan revealed diffuse thyroid gland enlargement and total thyroidectomy was performed. The histopathological examination revealed that mature fatty tissue was diffusely distributed throughout the thyroid gland, as well as among the hyperplastic follicles. Capsular formation or amyloid deposition were not observed. Nuclear grooves or intranuclear cytoplasmic inclusions were not observed. Accordingly, thyrolipomatosis was diagnosed. Albeit rare, various neoplastic and non-neoplastic thyroid lesions may contain mature fatty tissue. Therefore, thyrolipomatosis must be included in the differential diagnostic consideration of fat-containing lesions of the thyroid gland.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case report.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is a rare neoplasm characterized by morphological analogy to papillary thyroid carcinoma and abnormal expression of thyroid transcription factor-1 (TTF-1). We herein report a rare case of TL-LGNPPA with a review of its clinical, morphological and immunohistochemical characteristics. The patient was a 25-year-old Japanese woman complaining of a 2-year history of fever of unknown origin. There were no remarkable physical findings and the laboratory tests, including C-reactive protein levels, were normal. Laryngoscopy, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography identified a pedunculated mass at the roof of the nasopharynx. Histologically, the tumour exhibited papillary growth of cuboidal or columnar epithelium. Tubular architecture and a spindle cell component were also observed focally. Some tumour cells exhibited intranuclear cytoplasmic inclusions. Immunohistochemically, the neoplastic cells were positive for TTF-1, cytokeratin 7 and vimentin, but were negative for thyroglobulin. The Ki-67 labelling index (MIB-1 index) reached 5% in the most concentrated spot. The patient had neither local recurrence nor distant metastasis 3 years after removal of the tumour. In conclusion, TL-LGNPPA should be included it in the differential diagnosis of fever of unknown origin.

Epithelioid hemangioendothelioma: a study of 14 cytopathology cases

The cytopathologic diagnosis of the rare vascular tumor epithelioid hemangioendothelioma (EHE) in patients who have no previous history of EHE or who have a complicated and/or misleading disease history is challenging. Furthermore, few studies have described the cytopathology of EHE. Herein, we identify 14 cases of EHE from 10 patients, some of whom had a history of epithelial tumor, and provide a detailed report of the cytomorphology of EHE, discuss the tumor's differential diagnoses, and describe ancillary examinations that may be helpful in diagnosing EHE cytologically, especially in patients with a complex disease history. We retrieved the slides of 14 cases of EHE archived between 2002 and 2009 in our institution's cytology section. Conventional direct smears and cell block sections were prepared from most fine-needle aspiration samples and from all effusion samples. Cell block sections were subjected to immunostaining for vascular, mesothelial, and epithelial markers. EHE shared many morphologic features with other, more common tumors such as adenocarcinoma and mesothelioma. The defining cytologic feature of EHE was an intracellular lumen containing entrapped intact and degenerating erythrocytes, which was not present in every case. EHE cells were positive for the vascular markers CD34, CD31, factor VIII, and friend leukemia integration 1 transcription factor (FLI-1) and negative for epithelial and mesothelial markers. Clinicians provided information important to the diagnosis of EHE. Carefully examining the smear and cell block sections for morphologic features indicative of EHE (eg, prominent cytoplasmic vacuolization, intranuclear cytoplasmic inclusions, and intracellular lumen containing entrapped intact and degenerating erythrocytes), confirming these findings with immunocytochemical staining, and communicating with clinicians are all important to correctly diagnosing EHE.

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: Case report and literature review

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare neoplasm characterized by morphological analogy to papillary thyroid carcinoma and abnormal expression of thyroid transcription factor-1 (TTF-1). Here we report a novel case of TL-LGNPPA with literature review. The patient was a 43-year-old woman complaining of nasal obstruction. Laryngoscopic study and computed tomography identified a pedunculated mass located on the posterior edge of the left nasal septum. Histologically, the tumor consisted of papillary growth of cuboidal or columnar epithelium. Tubular architecture and a spindle cell component were also observed focally. Some tumor cells exhibited intra-nuclear cytoplasmic inclusions. Immunohistochemically, the neoplastic cells were positive for pancytokeratin (AE1/AE3), CK7, CK19, TTF-1, vimentin and HBME1, but negative for thyroglobulin, Pax8 and CK5/6. Ki67-labeling index reached 5% in the most concentrated spot. Despite the morphological and immunohistochemical similarity to papillary thyroid carcinoma, no BRAF V600E mutation was detected by mutation-specific immunohistochemistry. The patient had neither local recurrence nor distant metastasis 19 months after removal of the tumor.

Histopathological features of Papillary Thyroid Carcinoma with special emphasis on the significance of nuclear features in their diagnosis

Background: Papillary carcinoma (PTC) is the most common thyroid malignancy comprising 80-85%. In addition to papillary architecture, nuclear features like clear, ground glass or Orphan Annie-eyed appearance, oval shape, increased nuclear size, hypodense chromatin, intranuclear cytoplasmic inclusions, nuclear grooving, nuclear overlapping, and mitotic figures play a vital role in the diagnosis although some of the features may be seen in other diseases of thyroid. Objectives: To evaluate and establish the diagnostic significance of each nuclear feature in PTC. Settings and Design: Among the thyroidectomy specimens received in the department of pathology, only the PTC cases were chosen. Multiple sections were studied from the tumor by two different pathologists with a special emphasis on morphological and nuclear features. Statistical analysis: Fischer's exact test was done to find the correlation between the grading of nuclear features and cell population. Materials and Methods: Forty-one PTC cases were studied. Many H and E-stained slides of the tumor were studied by two different pathologists, and average of both observers was analyzed with special reference to nuclear features in classical and other variants of PTC. Results: The study evaluated that the ground glass nuclei, nuclear grooving, and nuclear overcrowding were the most common features seen in all (100%) cases though percentage of cells exhibiting these features varied from tumor to tumor. Other features mentioned above were less frequently encountered (42%-95%). Conclusion: In PTC, especially in variants, nuclear features are of utmost importance as they have to be differentiated from other thyroid diseases presenting with similar architectural morphology. Hence, more tissue sections have to be screened.

Intranuclear cytoplasmic inclusions are a specific feature of intraductal papillary mucinous neoplasms that distinguish contaminating gastric epithelium

Low-grade intraductal papillary mucinous neoplasms (IPMN) are challenging to diagnose because of an absence of reliable morphologic or immunohistochemical features to distinguish them from contaminating gastric foveolar epithelium. After noting intranuclear cytoplasmic inclusions (ICIs) in some cases of IPMN, we investigated whether ICIs could be used as a specific feature to distinguish IPMN from gastric foveolar epithelium. A consecutive cohort of 61 transduodenal endoscopic fine-needle aspirations of histologically or clinically verified pancreatic IPMNs without high-grade dysplasia from 2005 to 2012 were identified. A control cohort of 24 endoscopic fine-needle aspirations containing gastric epithelium was selected from transgastric specimens of nonpancreatic targets from the same period. Every fragment of mucinous epithelium in the 2 cohorts was examined in alcohol-fixed and cell block sections at high magnification to identify ICIs. ICIs were observed in 31% (19 of 61) of cases in mucinous epithelial fragments obtained by fine-needle aspirations from low-grade IPMNs. When present, they were seen in about 1% of all cells. No ICIs were identified in the control cohort of 24 patients with normal gastric epithelium (P = 0.001 Fisher exact test). BRAF mutation (V600E) testing was performed on 5 IPMN cases, and was negative in all cases including 2 with and 3 without ICIs. KRAS mutation testing was performed on 9 cases of IPMN cases. Two cases with ICIs tested positive for KRAS mutations. Four cases without ICIs also tested positive, and 3 cases without ICIs tested negative. ICIs are a specific morphologic feature found in about one third of low-grade IPMNs, but absent in gastric foveolar epithelium. There is no obvious molecular correlate with the presence of ICIs.