Morphologic spectrum of papillary carcinoma of the thyroid: role of cytology in identifying the variants

OBJECTIVE: To evaluate the efficacy of fine needle aspiration cytology (FNAC) in the diagnosis of morphologic variants of papillary carcinoma of the thyroid (PCT) and to determine the reasons for misdiagnosis in discrepant cases on cytology. STUDY DESIGN: Fine needle aspiration smears from 158 histologically proven cases of PCT were blindly reviewed and an attempt made to subclassify them into different variants on the basis of various architectural and morphologic features. Cytohistologic correlation was performed to assess the efficacy of cytology in correctly identifying these variants. RESULTS: In cases with satisfactory aspirates, the diagnosis of papillary carcinoma was correctly made in 112 of 139 (80.5%) histologically proven cases of PCT. Subclassification was correct in 87 of 96 (90.6%) cases of classic papillary carcinoma and in 25 of 43 (58.1%) of the other variants of PCT with adequate aspirates. Cytohistologic agreement was 100% in columnar cell variant (CCV) and high grade variant (HGV). Although there was overlap in the morphologic features of tall cell variant (TCV) and Hürthle cell variant, cytology correctly identified 60% and 76.4% of these cases, respectively. The accuracy of cytology was limited in diagnosing follicular variant as only 50% of these cases could be correctly typed on cytology. Nodular fascitis-like stroma and diffuse sclerosis variants could not be diagnosed on cytology. CONCLUSION: Though FNAC is of limited value in typing the variants of PCT due to overlapping morphologic features, it can provide clues to the diagnosis in certain aggressive variants such as TCV, CCV and HGV. Early diagnosis in these cases can assist clinicians with management.     

Intranuclear cytoplasmic inclusions and nuclear grooves in fine needle aspiration smears of papillary thyroid carcinoma and its variants: advantage of the count under an oil-immersion objective over a high-power objective

OBJECTIVE: To determine the advantage of examining fine needle aspiration (FNA) smears of papillary thyroid carcinoma (PTC) under a 100 x oil-immersion objective, which is capable of optically sectioning the cells. STUDY DESIGN: Two hundred neoplastic cells were counted under a high-power (40x) objective as well as oil-immersion (100x) objective in 54 PTC cases classified into variants: 14 follicular neoplasms, 8 Hürthle cell neoplasms, 5 medullary thyroid carcinomas and 9 hyperplastic lesions. The counts of cells with 2 important diagnostic features of PTC, intranuclear cytoplasmic inclusions (INCIs) and grooved nuclei, were compared between various groups and between high-power and oil-immersion objectives in each group. RESULTS: Cytomorphologic features, such as INCI and nuclear grooves, were visible usually under 2 or 3 focal planes under the oil-immersion objective as opposed to a single plane under the high-power objective. In PTC cases, the mean cell count, 10.1 (+/- 1.75 SE) with INCIs, under the oil-immersion objective was significantly higher than the count, 6.1 (+/- 1.32 SE), under the high-power objective (p = 0.023). INCIs were not observed under the high-power objectives in 11 (20.4%) PTC cases, but in 5 (45.5%) of these they were visible under the oil-immersion objective. In PTC the mean cell count, 88.0 (+/- 4.96 SE), with grooved nuclei under the oil-immersion objective was also significantly higher than the count, 69.5 (+/- 4.87 SE), under the high-power objective (p = 0.010). Under the high-power objective, < 20.0% of cells with grooved nuclei were observed in 12 (22.2%) cases of PTC. However, examination under the oil-immersion objective revealed > or = 20.0% cells with grooved nuclei in 9 (75%) of these. In PTC the mean cell counts with INCIs as well as grooved nuclei under the oil-immersion objective were significantly higher than those of follicular neoplasms, Hürthle cell neoplasms, medullary carcinoma and hyperplastic lesions. CONCLUSION: In PTC, examination of FNA smears for INCIs and grooved nuclei under an oil-immersion objective was diagnostically more useful as compared to a high-power objective.     

Columnar cell variant of papillary thyroid carcinoma. Report of a case with cytologic findings

BACKGROUND: The columnar and tall cell variants of papillary thyroid carcinoma (PTC) are uncommon variants and have generally been regarded as more aggressive forms in comparison to the more common classic papillary and follicular subtypes. Cytologic diagnosis of these rare variants is elusive since the characteristic nuclear features of the usual papillary thyroid carcinoma are very often absent or inconspicuous. We present a case of the columnar cell variant of PTC in a young woman that demonstrates the diagnostic challenge. CASE: A 24-year-old woman presented with a solitary, 3-cm mass in the left aspect of the thyroid. The aspirate consisted of a moderately cellular sampling of sheets, papillary clusters and microfollicles of cells with oval nuclei and uniform, finely granular chromatin. These cells were arranged in a peudostratified manner around well-defined fibrovascular cores. There were no intranuclear inclusions or well-defined nuclear grooves in the cells of the aspirate. There was also absence of colloid despite the presence of well-formed follicles. The resected thyroid revealed a columnar cell variant of PTC. CONCLUSION: The cytologic features of columnar cell-type PTC are at variance with those of classic PTC and are elusive in fine needle aspiration cytology. It is the lack of classic cytologic features of PTC that is distinctly apparent, yet it is the monomorphism of cells in the aspirate, their papillary configuration and their pseudostratification in well-formed fibrovascular cores that are the keys to the diagnosis. Immunohistochemical staining to rule out other thyroid neoplasms can be performed to aid in the diagnosis.     

Fine-needle aspiration of thyroid nodules: proteomic analysis to identify cancer biomarkers

At present, the clinical and pathological analysis used in the diagnosis of papillary thyroid cancer (PTC) are insufficient to discern tumor behavior, and new diagnostic and prognostic markers need to be identified. In this study, we performed a comparative proteome analysis to examine the global changes of fine needle aspiration fluid (FNA) protein patterns of two variants of malignant PTC (classical variant PTC (cPTC) and tall cell variant PTC (TCV)) with respect to the controls. Changes in protein expression were identified using two-dimensional electrophoresis (2DE) and peptide mass fingerprinting via MALDI-TOF mass spectrometry (MS), as well as Western blot analysis. A statistical significant up-regulation of 17 protein spots in cPTC and/or TCV with respect to controls was demonstrated. These proteins included transthyretin precursor (TTR), ferritin light chain (FLC), proteasome activator complex subunit 1 and 2, alpha-1-antitrypsin precursor, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase chain B (LDH-B), apolipoprotein A1 precursor (Apo-A1), annexin A1, DJ-1 protein and cofilin-1. In addition, 12 protein spots were found exclusively in cPTC and three exclusively in TCV. These latter proteins (ferritin heavy chain (FHC), peroxiredoxin 1 (PRX1) and 6-phosphogluconate dehydrogenase (6-PDGH)) correspond to stress response proteins and, until now, had not been described in thyroid tumors. These findings illustrate the potential use of FNA proteomics to identify protein changes associated with thyroid cancer and to advance potential protein biomarkers in the diagnostic classification of the disease.     

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.     

Papillary carcinoma of thyroid: classical and variants

Papillary carcinoma, the commonest primary cancer of thyroid, exhibits a broad morphological spectrum. In this review, the clinicopathological features of papillary carcinoma, classical and its variants (follicular, solid, cribriform, variant with exuberant nodular fasciitis-like stroma, encapsulated, diffuse sclerosing, diffuse follicular, tall cell, columnar cell, oxyphil cell, "dedifferentiated", occult, latent and microcarcinoma) are summarized.     

Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category

A. Mahajan, X. Lin and R. Nayar Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category Objective: The Bethesda System of Reporting Thyroid Cytopathology classifies the indeterminate categories based on their differing risks of malignancy, as atypia of undetermined significance (AUS), follicular neoplasm/suspicious for follicular neoplasm (FLUS) and suspicious for malignancy. The vast majority of cases of the last category are suspicious for papillary thyroid carcinoma (PTC). The aim of the present study was to identify the pitfalls and clues to improve the usage of the suspicious category as well as improve its outcome of malignancy. Methods: We reviewed the cytological features on air dried Diff‐Quik® and alcohol‐fixed Papanicolaou smears from 54 thyroid fine needle aspirates (FNAs) with surgical follow‐up that were originally diagnosed as suspicious. Procedure data/specimen adequacy was correlated and follow‐up histology reports were reviewed after our cytological review was completed. Incidental PTC that was not the target of the FNA was excluded from the calculations for correlation. Results: In our cytological review, we retained a diagnosis of suspicious in 18 of the 54 cases and the remaining 36 were re‐categorized as follows: 6 malignant, 10 neoplasm (which is used in our centre instead of FLUS) and 20 AUS. The reasons for overcall of suspicious cases included pseudopapillae, syncytial sheets, nuclear grooves and pinpoint nucleoli in chronic lymphocytic thyroiditis and Hürthle cell neoplasms, and intranuclear inclusions in parathyroid adenoma, hyalinizing trabecular adenoma and mesenchymal repair. The primary reasons for undercall of PTC as suspicious included cystic aspirates with minor features of PTC such as histiocytoid cells, bubblegum colloid, syncytial sheets and cellular swirls. Cases with cytoplasm similar to Hürthle cells were also noted to cause difficulty in accurate classification. Conclusions: Recognition of these pitfalls and clues can help improve diagnosis, patient treatment and consequently reduce the number of unnecessary thyroidectomies.     

Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer

Background

Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown.

Method and Findings

74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 ± 6 vs 0.3 ± 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 ± 0.6 vs 0.3 ± 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells.

Conclusion

In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules.     

Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases

S. Mandal, and S. Jain
Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases Objective: An adenoid cystic pattern in thyroid tumours is a rare finding that may be seen in papillary carcinoma of thyroid (PCT), the follicular variant of PCT (FV‐PCT), a rare cribriform‐morular variant of papillary carcinoma of thyroid (CMV‐PCT) and follicular carcinoma. There is little published cytological literature describing these patterns. We report four cases of PCT with this unusual pattern. Methods: Fine needle aspiration (FNA) cytology was performed on four patients with a neck lump using a 22‐G needle; smears were stained with Giemsa and Papanicolaou stains. Immunocytochemical staining for thyroglobulin was done in all cases. Results: The patients were female and ranged in age from 18 to 46 years. They presented with a gradually increasing mass in the neck. FNA smears in all cases showed nuclear features of PCT. There were also prominent follicular areas with hyaline globules in some of the cell clusters reminiscent of adenoid cystic carcinoma and, in places, morula‐like groups of neoplastic cells were also seen. Immunocytochemistry for thyroglobulin was positive in all cases but negative in the hyaline globules. Conclusions: Adenoid cystic areas with morula‐like groups in PCT are a rare finding. Cytopathologists and clinicians should be aware of these distinct features in thyroid tumours to avoid diagnosing metastatic adenoid cystic carcinoma. It is also important to rule out CMV‐PCT since that variant is mostly associated with familial adenomatous polyposis, although sporadic occurrence is known.     

BRAF initiating mutations in the papillary thyroid carcinoma

Among genetic alterations most important for the initiation of papillary thyroid carcinoma (PTC) is mutation T1799A in the BRAF gene which is the most frequent event (54.5%) in this type of thyroid cancer. It is seen in all stages, from microcarcinoma through clinically overt disease to anaplastic cancer. It has been shown that BRAF mutation is correlated with PTC histotype. It is identified most frequently in classical PTC and in tall cell variant. Moreover, BRAF mutation is described more often in older patients, whereas in young patients RET/PTC rearrangements dominate. In PTC cases with BRAF mutation V600E the prognosis is poorer, with more cancer invasiveness, metastasis and recurrence. The presence of BRAF mutation is related to the specific gene expression signature, different than in cancer cases showing RET/PTC rearrangement or no known initiating mutation.     

Papillary Hyperplastic Nodule: Pitfall in the Cytopathologic Diagnosis of Papillary Thyroid Carcinoma

ObjectiveTo identify the pitfalls of overdiagnosing papillary formation as papillary thyroid carcinoma (PTC) in thyroid cytology specimens.MethodsPatients with papillary hyperplastic nodules who had preoperative fine-needle aspiration biopsy (FNAB) were selected for this study. All patients had been diagnosed as having either PTC or lesions suggestive of PTC on preoperative FNAB. Pathology reports, surgical reports, and cytopathology slides were reviewed and analyzed for demographic data, nature of surgery, and pathologic features.ResultsSix women and 2 men with a mean age of 49 years (range, 16-79 years) were included. The lesion size ranged from 1.0 to 3.5 cm. Four patients were diagnosed as having PTC and 4 as having lesions suspicious for PTC. FNAB specimens were available for review in 6 cases. Surgical pathology slides were reviewed in all cases. When cytologic material was evaluated for the morphologic features that led to the misdiagnosis of PTC by comparing it with FNAB specimens of classic variant of PTC, the specimens from these patients showed follicular cells arranged in short, nonbranching papillae in a background of watery colloid and macrophages. The follicular cells were round and demonstrated oncocytic change with nuclear enlargement, prominent central nucleoli, nuclear chromatin clearing, and intranuclear grooves.ConclusionsCaution should be exercised rendering the diagnosis of PTC on FNAB samples when a thyroid lesion shows papillary configurations and oncocytic cells and if convincing nuclear features of PTC are not present. Furthermore, some morphologic features on thyroid aspiration can help differentiate these cases from true PTC. (Endocr Pract. 2008;14:863-868)     

Cytopathology of Follicular Tumours of the Thyroid With Clear Cell Change

A retrospective cytological study of nine follicular tumours of the thyroid with clear cell change was undertaken. In five clear cell adenomas and one moderately differentiated clear cell follicular carcinoma the epithelial cells occurred singly or in sheets and clusters; they sometimes assumed a trabecular or follicular pattern. The cells usually had pale diffusely vacuolated cytoplasm with ill-defined boundaries, a variable degree of anisonucleosis, nucleolar enlargement, and nuclear overlapping. Smears from a signet-ring cell adenoma contained in addition a few cells with large cytoplasmic vacuoles and compressed eccentric nuclei. In these cases a cytological diagnosis of 'follicular lesion' (or follicular neoplasia), clear cell type or signet-ring cell type, was given. A cytodiagnosis of 'carcinoma' was made only in the poorly differentiated follicular carcinoma-clear cell variant studied which showed unequivocal features of malignancy. Features suggestive of thyroid cyst, nodular goitre, Hashimoto's thyroiditis, and cell hyperactivity (marginal vacuoles, 'fire flare') were also found in the aspirated specimens of these cases of clear cell tumour of the thyroid.     

Cytopathology of the tall cell variant of thyroid papillary carcinoma.

The tall cell variant of thyroid papillary carcinoma differs from classic papillary carcinoma in its more aggressive clinical behavior, cell type (columnar amphophilic to oxyphilic) and higher frequency of stromal lymphoid infiltrate. A retrospective study of three such cases was made, with an emphasis given to the utility of fine needle aspiration cytology in their identification. Aspirates revealed papillary fronds and cyanophilic and oxyphilic neoplastic cells with a high proportion of nuclear grooves and cytoplasmic inclusions. These nuclear details allowed a specific diagnosis of papillary carcinoma with oxyphil cells as compared to oxyphilic cell follicular tumors. Smears from two cases showed, in addition, lymphoid cells and multinucleate giant cells. In them a diagnosis of coexisting Hashimoto's disease, granulomatous thyroiditis or inflammatory tumor stroma could not be excluded cytologically.     

Novel secondary Ig VH gene rearrangement and in-frame Ig heavy chain complementarity-determining region III insertion/deletion variants in de novo follicular lymphoma

Human germinal center B cell tumors retain the ability of their nontransformed counterparts to somatically hypermutate Ig V genes by nucleotide substitution. Among a survey of 60 primary previously untreated, clonal, follicular lymphomas we have identified a rare V(H) rearrangement variant and two other in-frame nucleotide insertion/deletion variants within complementarity-determining region III of the Ig heavy chain. The neoplastic origin of the V(H) rearrangement variant was directly demonstrated in cells isolated by microdissection from malignant follicles. In all three cases a common clonal origin for the variants was demonstrated by complementarity-determining region III nucleotide sequence homology and shared somatic mutations in germline encoded positions in framework region IV. The monoclonal nature of the tumors was independently confirmed by demonstrating a single t(14;18) translocation breakpoint in the two cases with a detectable translocation. All the variants occurred in functional V(H) rearrangements, which in two cases were directly shown to encode functional Ab molecules. Both recombination-activating genes 1 and 2 were expressed in lymph node tumor cells containing the V(H) rearrangement variant, although recombination-activating gene expression among a panel of lymphomas was not limited to this variant.     

An Appraisal of Proliferation and Apoptotic Markers in Papillary Thyroid Carcinoma: An Automated Analysis

Introduction

Proliferation and apoptosis are opposing processes by which the cell numbers are kept in a delicate balance, essential for tissue homeostasis, whereas uncontrolled growth of cells is a hallmark of cancer. Papillary thyroid cancer (PTC) is the commonest type of thyroid cancer, with some PTC following an indolent course, whereas the other ones are more aggressive.

Aim

To evaluate respective contribution of proliferation and apoptosis in the tumorigenesis of PTC by automated analysis.

Materials and Methods

We investigated the immunolabeling of phosphorylated histone H3 (pHH3), cyclin D1, active caspase-3, and bcl-2 in thirteen cases each of metastatic PTC, follicular variant of PTC (FVPTC), papillary microcarcinoma (PMC) and well differentiated tumor of uncertain malignant potential (WDT-UMP). FVPTC cases comprised seven encapsulated and six unencapsulated cases.

Results

Proliferation, as assessed by pHH3 and cyclin D1 immunolabeling, was increased in all PTC variants, including the putative precursor lesion WDT-UMP, compared to normal thyroid tissue. pHH3 was immunolabeled in more cells of metastatic PTC than of PMC and of encapsulated FVPTC. Surprisingly, metastatic PTC and unencapsulated FVPTC also demonstrated more cleaved caspase-3 immunolabeled cells than the other types. In contrast, increased expression of bcl-2 protein was seen in normal thyroid areas, encapsulated FVPTC and PMC as compared to metastatic PTC. Metastatic PTC shows higher proliferation than other types of PTC but unexpectedly also higher apoptotic levels. Similar results were also seen with unencapsulated FVPTC, thus suggesting that unencapsulated FVPTC has a potential for adverse outcome. Bcl-2 was immunolabeled in a low percentage of cells in WDT-UMP.

Conclusions

The expression of the proliferative protein pHH3 together with the apoptotic marker cleaved caspase-3 may indicate an aggressive behaviour of PTC and loss of apoptosis inhibition by bcl-2 protein can further amplify the role of these proteins in tumor progression. Both cyclin D1 and bcl-2 could prove to be interesting markers of PTC precursor lesions. Automated/digital image quantification approach helps in refining the diagnostic accuracy.     

Multinucleated giant cells in fine needle aspirates. Can they help differentiate papillary thyroid cancer from benign nodular goiter?

OBJECTIVE: To determine whether multinucleated giant cells (MGCs) in fine needle aspirates can help differentiate papillary thyroid carcinoma (PTC) from benign nodular goiter (BNG). STUDY DESIGN: Specimens from 100 cases of PTC and 100 cases of BNG with surgical and pathologic proof were randomly retrieved. The morphologic characteristics and frequency distribution of the maximal size and number of MGC nuclei were analyzed. A retrospective review of medical records was also undertaken. RESULTS: MGCs were twice as frequent (40%) in PTC than in BNG (26%) (odds ratio = 1.90). Most MGCs in BNG tended to be smaller and ovoid, with foamy cytoplasm, and had fewer nuclei. No MGC in BNG was > 116 microns in diameter or had > 27 nuclei. In contrast, MGCs in PTC were more diverse in size, shape, cytoplasm and number of nuclei. No significant association was found between the presence or nature of MGCs and disease extent in PTC. CONCLUSION: The presence of large MGCs with dense cytoplasm in a thyroid nodule without clinical evidence of thyroiditis should prompt careful exclusion of associated PTC.     

Cytoplasmic colloid inclusions in thyroid lesions: a cytomorphological study based on fine needle aspiration

INTRODUCTION: Intracytoplasmic lumens (ICL) with or without magenta material and transgressing vessels are features of Hürthle cell neoplasms (HCN). After detection of intracytoplasmic colloid inclusions (CIs) including targetoid (magenta) body-like structures in the Hürthle cells (HC) in a case of Hashimoto's thyroiditis (HT), we reviewed cases of HT, thyroid neoplasms, hyperplastic nodules (HN) and colloid goitres to determine the frequency of these structures. Further, an attempt was made to find out the significance of CIs. METHODS: FNA smears of 120 HT, 101 colloid goitres, 11 HN, and 76 neoplastic goitres were examined. The presence of CIs and empty ICL were noted in epithelial cells in these lesions. An attempt was made to find out the difference between HT with and without CIs in respect of various cytomorphologic features. The groups were compared using the Fisher's exact test of probability. RESULTS: The CIs were present in 36 (30.0%) of HT, 26 (34.2%) of neoplastic goitres, 3 (27.3%) of HN, and 4 (4.0%) colloid goitres. As compared to colloid goitres, CIs were present in a significant higher number of cases in HN (P = 0.0202), neoplastic goitres (P < 0.0001), and HT (P < 0.0001). Among neoplasms the frequency of CIs in HCN (75.0%) was significantly higher than that of papillary thyroid carcinoma (PTC) (33.3%, P = 0.0466), and follicular neoplasm (14.3%, P = 0.0083). The CIs were more frequent in HC in HT and HCN but in follicular cells (FC) in other lesions. The HT cases with CIs differed significantly from those without CIs in respect of HC and their cellularity, cellularity of reactive lymphoid cells, extracellular colloid and empty ICL. CONCLUSION: Care should be taken not to diagnose HT cases with an excessive Hürthle cell component and CIs, and PTC cases with Hürthlization and CIs, as HCN in FNA smears. Based on review of the literature and our findings, it is suggested that the Hürthle cell metaplasia in HT is a survival response of FC and the presence of CIs in Hürthle cell may represent their limited ability to synthesize colloid.     

Characteristics of the active and inactive variants of Actinomyces sp. 26-115, a producer of actinomycin C

Two natural variants, i.e. No. 1 and No. 2, not producing actinomycin were isolated from cultures of the actinomycin C-producing organism Actinomyces sp. 26-115. Variant No. 1 differed from the active variant by the growth dynamics and colony morphology. Variant No. 2 was close to the active variant by the growth dynamics. It was shown with electron microscopy that the cells of variant No. 1 differed from those of the active variant in the number and form of the mycelial septa, more even and compact structure of the cell walls and higher sensitivity to actinomycin. Still, they were more stable to the effect of lysozyme and ultrasound. The cell walls of the inactive variant No. 1 gradually lost teichoic acid during development, while the loss of peptidoglycan was observed only on transfer to the stationary phase. The cell walls of the active variant lost teichoic acid and peptidoglycan at the same time on transfer to the stationary phase. Peptidoglycans of both variants contained diaminopimelic acid (the configuration of which was not determined) and glycine (1:1) as differentiating amino acids. The two adjacent tetrapeptides were joined with one glycine radical. The peptidoglycan peptide chains of both variants contained muramic, glutamic and diaminopimelic acids and alanine (1:1:1:2). The peptidoglycans of the inactive variant No. 1 contained in addition valine and isoleucine. However, it is hardly probable that they are contained by the peptidoglycan peptide chains.     

Regulation of proximal tubular epithelial cell CD44-mediated binding and internalisation of hyaluronan

BACKGROUND: Increased expression of the connective tissue polysaccharide hyaluronan (HA) in the renal corticointerstitium is associated with progressive renal fibrosis. Numerous studies have demonstrated involvement proximal tubular epithelial cells in the fibrotic process and in the current study we have characterised their expression of the HA receptor, CD44, and examined changes in CD44 expression and function in response to either IL-1beta or glucose. METHODS: Characterisation of CD44 splice variant expression was carried out in primary cultures of human proximal tubular cells (PTC) and HK2 cells. Binding and internalisation HA was examined by addition of exogenous of fluorescein-HA (fl-HA), and expression of CD44 examined by immunoblot analysis and flow cytometry. Alteration in "functional" CD44 was determined by immunoprecipitation of CD44 following stimulation in the presence of fl-HA. RESULTS: PTC, both primary culture and the PTC cell line, HK2, express at least 5 CD44 splice variants, the expression of which are not altered by addition of either IL-1beta or 25mM D-glucose. Addition of either stimulus increased cell surface binding and internalisation of fl-HA and increased expression of functionally active CD44. Increased binding and internalisation of fl-HA, was blocked by anti-CD44 antibody, and by the inhibition of O-glycosylation. CONCLUSIONS: The data demonstrate that stimuli inducing PTC HA synthesis also regulate PTC-HA interactions. Furthermore increased HA binding and internalisation is the result of post-translational modification of CD44 by O-glycosylation, rather than by alteration in expression of CD44 at the cell surface, or by alternate use of CD44 splice variants.     

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis

Objective: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. Study Design: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. Results: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). Conclusions: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.