Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis.

Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). TICs from primary NSCLC tumors express high levels of the oncogenic stem cell factor LIN28B and GLDC, which are both required for TIC growth and tumorigenesis. Overexpression of GLDC and other glycine/serine enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. We found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. In the clinic, aberrant activation of GLDC correlates with poorer survival in lung cancer patients, and aberrant GLDC expression is observed in multiple cancer types. This link between glycine metabolism and tumorigenesis may provide novel targets for advancing anticancer therapy.

Dynamic altruistic cooperation within breast tumors.

BACKGROUND: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. METHODS: MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients. Cancer cell lines ectopically expressing candidate miRNA were used in co-culture experiments and treated with docetaxel. Ecological parameters like relative survival and relative fitness were assessed using flow cytometry. Functional studies and characterization performed in vitro and in vivo include proliferation, iTRAQ-mass spectrometry, RNA sequencing, inhibition by small molecules and antibodies, siRNA knockdown, CRISPR/dCas9 inhibition and fluorescence imaging of promoter reporter-expressing cells. Mathematical modeling based on evolutionary game theory was performed to simulate spatial organization of cancer cells. RESULTS: Opposing cancer processes underlie altruism: an oncogenic process involving secretion of IGFBP2 and CCL28 by the altruists to induce survival benefits in neighboring cells under taxane exposure, and a self-sacrificial tumor suppressive process impeding proliferation of altruists via cell cycle arrest. Both processes are regulated concurrently in the altruists by miR-125b, via differential NF-κB signaling specifically through IKKß. Altruistic cells persist in the tumor despite their self-sacrifice, as they can regenerate epigenetically from non-altruists via a KLF2/PCAF-mediated mechanism. The altruists maintain a sparse spatial organization by inhibiting surrounding cells from adopting the altruistic fate via a lateral inhibition mechanism involving a GAB1-PI3K-AKT-miR-125b signaling circuit. CONCLUSIONS: Our data reveal molecular mechanisms underlying manifestation, persistence and spatial spread of cancer cell altruism. A minor population behave altruistically at a cost to itself producing a collective benefit for the tumor, suggesting tumors to be dynamic social systems governed by the same rules of cooperation in social organisms. Understanding cancer cell altruism may lead to more holistic models of tumor evolution and drug response, as well as therapeutic paradigms that account for social interactions. Cancer cells constitute tractable experimental models for fields beyond oncology, like evolutionary ecology and game theory.

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

BRAF mutation in papillary thyroid cancer-Prevalence and clinical correlation in a South-East Asian cohort.

OBJECTIVE: BRAF mutation is the commonest mutation seen in papillary thyroid cancer (PTC), but its prevalence and clinical significance vary across countries. We aim to evaluate the prevalence and clinico-pathological correlation of BRAF mutation in PTC patients at our centre. STUDY DESIGN: Retrospective cohort study of 75 consecutive archival thyroid specimens, whereby BRAF mutation was detected using a polymerase chain reaction (PCR) technique and correlated with clinical and pathological features and outcomes. SETTING: Tertiary university hospital in Singapore. PARTICIPANTS: A total of 75 consecutive histologically proven archival thyroid specimens from patients who underwent thyroidectomy for PTC were accrued for this study. MAIN OUTCOME MEASURES: Main outcome is to determine the prevalence of the BRAF mutation in our South-East Asian population. Secondary aim is to correlate the mutational status with adverse pathological features like histological variants, multi-focality, lymphovascular invasion and extra-thyroidal extension, clinical features like demographics, TNM stage, recurrence and survival, as well as treatment details like type of surgery performed and radioiodine doses. RESULTS: BRAF mutation was detected in 56% (42/75) of PTC. All but one BRAF-mutated PTC had the BRAFV600E mutation. BRAF-mutated tumours were associated with an advanced T-stage (P = 0.049) and were more likely to have a central neck dissection (P = 0.036). There was no significant correlation between BRAF mutation status and clinical outcomes. CONCLUSION: The prevalence of BRAF mutation is 56%. BRAF mutation-positive tumours were associated with locally advanced disease, but not poorer survival.

Pilomatricoma of the cheek: a benign tumor mimicking metastatic squamous cell carcinoma on FDG PET/CT.

BACKGROUND: Pilomatricomas are benign skin tumors originating from hair matrix cells in the dermal layer of the skin, especially in the head and neck region. They may mimick malignant lesions on fine-needle aspirate cytology. METHODS: This is a case report of a pilomatricoma of the cheek which was initially diagnosed as squamous cell carcinoma on fine-needle aspirate cytology. As part of the staging work-up, a PET/CT scan was performed, revealing a FDG-avid superficial cheek lesion and also an ipsilateral FDG-avid level II cervical lymph node, giving the impression of metastatic squamous cell carcinoma. RESULTS: The cheek lesion, as well as the cervical lymph node was excised. The final histology showed benign pilomatricoma and reactive lymphadenopathy. CONCLUSION: Pilomatricoma should be considered as an uncommon differential diagnosis for an FDG-avid cutaneous lesion on PET/CT, even in the presence of ipsilateral FDG-avid cervical lymphadenopathy.

Impact of CD151 overexpression on prognosis and therapy in non-small cell lung cancer patients lacking EGFR mutations.

This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)-induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF-induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti-proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR-targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations.

Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.

BACKGROUND: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. METHODS AND RESULTS: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. CONCLUSION: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Pitfalls in Lymph Node Fine Needle Aspiration Cytology.

Background Fine needle aspiration cytology (FNAC) is an accurate, minimally invasive and cost-effective biopsy method for enlarged lymph nodes. While the role of lymph node FNAC in the diagnosis of infectious or reactive conditions and metastatic malignancy is unquestioned, differing views still exist on its role in the diagnosis of lymphoma. Nevertheless, regardless of the practice setting, pitfalls and potential for error exist, and it is incumbent upon the pathologist to be aware of these pitfalls; as this is the first line of defence against errors. Summary This discussion will focus on potential interpretational errors, specifically highlighting scenarios leading to false negative and false positive diagnosis and errors in tumour classification, with an emphasis on cytomorphology. Potential entities that may fly below the radar of the pathologist - so-called "off radar entities" are also discussed, as a reminder to consider broad differentials in cases with unusual morphologic features. Some reasons for false negative diagnoses include low grade lymphomas that mimic a mixed, polymorphous reactive lymphoid population; or aspirates with a paucity of lesional cells, either through sampling error or the intrinsic nature of the entity e.g. nodular lymphocyte predominant Hodgkin lymphoma. Some of the potential causes of false positive diagnoses that are discussed include viral-associated lymphadenopathy, Kikuchi-Fujimoto lymphadenitis or benign adnexal lesions mimicking metastatic malignancy. Errors in tumour classification covered include metastatic carcinoma, sarcoma, melanoma and lymphoma mimicking each other, and Hodgkin lymphoma and its mimics. Finally, less common entities such as follicular dendritic cell sarcoma and others are briefly mentioned, to remind us of conditions that may slip under our diagnostic radar. Key Messages A systematic review of diagnostic pitfalls and traps are elucidated here, with some tips to avoid these traps. The triple approach to the diagnostic workup is emphasised; which includes rigorous clinicopathologic correlation, attention to cytomorphology and judicious application of ancillary tests.

Spiradenocarcinoma with low-grade basal cell adenocarcinoma pattern: report of a case with varied morphology and wild type TP53.

We present a patient with a 2-cm spiradenocarcinoma of the left arm resembling low-grade salivary gland basal cell adenocarcinoma. In addition to showing attributes of conventional spiradenoma, the benign component showed prominent areas of cystic change with focal apocrine differentiation, glands with and without mucinous differentiation, clear cell change and focal adenoid cystic carcinoma-like areas. The malignant component was composed of nodules of basaloid cells arranged in sheets with variable tendency to luminal differentiation. The nuclear atypia was low-grade, and the mitotic index was high in the malignant component (to 8/10 high power fields). Immunohistochemically, there was diffuse but variable positivity for cytokeratin 7 in both the benign and malignant components. Epithelial membrane antigen was focally positive, highlighting cells with ductal (luminal) differentiation. Expression of p63 was observed in 50 and 80% of the cells in the benign and malignant components, respectively. Calponin was negative. The proliferative index (MIB-1/Ki-67) was <3% in the benign component and up to 10% in the malignant component. Although the malignant component displayed patchy areas with nuclear p53 immunoreactivity with variable intensity, no mutation in the TP53 gene was identified.

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

BACKGROUND: The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. METHODS: Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). RESULTS: A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P = .0142) and SUMP NOS (P = .0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P = 1.0000) and O1 and O2 (65.2% vs 48.7%, P = .2349). CONCLUSIONS: The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P = .0142) and SUMP NOS (31.9%, P = .0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

Human papillomavirus infection in lung and esophageal cancers: analysis of 485 Asian cases.

The role of human papillomavirus (HPV) in the development of lung and esophageal cancer remains inconclusive, which is in contrast to the established role HPV plays in the development of uterine cervical cancer. One of the reasons for this is the difference among reported HPV infection rates in these cancers. An analysis of 485 lung and esophageal cancers (176 lung squamous cell carcinoma, 128 lung adenocarcinoma, 181 esophageal carcinoma) in eight institutions in Asia (Tokyo, Kochi, Kagoshima, and Okinawa, Japan; Seoul and Daegu, Korea; Changhua, Republic of China (Taiwan); Singapore, Singapore) was carried out in order to clarify infection rates with HPV. Samples were examined in one laboratory of the Department of Pathology, the University of Tokyo, Japan in order to avoid inter-laboratory variation using a combination of polymerase chain reaction and in situ hybridization (ISH). HPV was found in 6.3%, 7%, and 9.4% of patients with lung squamous cell carcinoma, lung adenocarcinoma, and esophageal cancer, respectively. Among the geographic areas surveyed, Kagoshima exhibited a significantly higher prevalence of HPV infection in cases of esophageal carcinoma (24.1%). There was no geographical difference in the infection rates of HPV in lung carcinomas. Subtype-specific ISH was also performed, which identified the high-risk HPV types 16/18 in the majority (75.7%) of the patients with lung and esophageal cancer positive for HPV.

Ectopic Cervical Thyroid Tissue Affected by Fibrosing Hashimoto's Thyroiditis Mimicking Multifocal Metastatic Papillary Thyroid Carcinoma-A Hard Lesson Learnt from an Unusual Case.

We describe a case of ectopic cervical thyroid tissue which was involved by fibrosing Hashimoto's thyroiditis and which mimicked metastatic papillary thyroid carcinoma both on fine needle aspiration cytology and biopsy. The patient underwent total thyroidectomy which revealed fibrosing Hashimoto's thyroiditis, but no carcinoma. The entire thyroidectomy specimen was submitted for histopathological assessment. Even in the resected thyroidectomy specimen, there were cytological changes that were strongly reminiscent of papillary thyroid carcinoma. However, interpreted in the correct clinico-pathological context, these cytological alterations were deemed to be reactive secondary to the fibro-inflammatory process.

In vivo demonstration of a novel non-invasive model for inducing localized hypothermia to ameliorate hepatotoxicity.

Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro. However, there are concerns regarding its clinical relevance as it remains a challenge to perform selective liver cooling in a non-invasive manner. To reconcile this dilemma, we propose the use of pulsed cooling for regional hypothermic conditioning in liver. This involves intermittent cooling applied in pulses of 15 min each, with a one-hour recovery interval between pulses. Cooling is achieved by applying ice packs to the cutaneous region overlying the liver. Through an in vivo C57BL/6NTac mouse study, we demonstrated the feasibility of attaining localized hypothermia close to the liver while maintaining core body temperature. This has successfully ameliorated acetaminophen-induced liver injury based on the liver function tests, liver histology and total weight change. Collectively, we provide a proof of concept for pulsed external localized cooling as being clinically actionable to perform induced selective hypothermia.

COVID-19 post-vaccination lymphadenopathy: Report of cytological findings from fine needle aspiration biopsy.

The coronavirus COVID-19 pandemic has spurred the rapid development of vaccines, with vaccination programmes already underway in many countries. Regional lymphadenopathy is one of the documented side effects of vaccination. We document the fine needle aspiration cytological findings of an enlarged supraclavicular lymph node in a 34-year-old Asian female following the first dose of the Pfizer-BioNTech COVID-19 mRNA vaccine, which appears to be the first such report in a premorbidly well patient with no known history of malignancy. The cytological findings featured a reactive pattern in keeping with follicular hyperplasia, with prominent germinal centre elements including lymphohistiocytic aggregates and tingible-body macrophages. Despite an increased proportion of larger lymphocytes, the overall pattern was in keeping with a reactive pattern, bearing in mind the temporal and geographic relation to the vaccination injection. In instances of localised lymphadenopathy, particularly in supraclavicular or axillary locations, pathologists should be cognizant of the possibility of post-vaccination reactive lymphadenopathy, and seek clinical and radiological hints favouring a benign process, whilst recognising potential morphological overlaps with lymphoproliferative disorders. Awareness of this diagnostic pitfall is especially important as COVID-19 vaccination coverage is ramped up worldwide, leading to an expected increase in incidence of post-vaccination reactive lymphadenopathy.

Cytologic diagnosis of medullary thyroid carcinoma in the Asia-Pacific region.

BACKGROUND: The accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to the rarity of tumor and variable cytologic appearance. The Asian experience with diagnosing MTC by fine-needle aspiration (FNA) was scarcely reported. METHODS: Cases of MTC with available FNA slides were enrolled from 13 hospitals representing 8 Asia-Pacific countries. Clinicopathological information, including sample preparation technique, staining method, original cytologic diagnosis and review diagnosis were collected. RESULTS: Of a total of 145 MTC cases retrospectively recruited, 99 (68.3%) were initially interpreted as MTC/suspicious for MTC (S-MTC). The distribution of original FNA diagnostic categories was not associated with the staining method or sample preparation technique. The staining methods used were Papanicolaou, hematoxylin-eosin and Romanowsky stains. Liquid-based cytology (LBC) was used only in three countries. After reviewing all cases, the diagnostic rate of MTC/S-MTC increased to 91.7% (133/145). Cases with initially unrecognized MTC had either marked pleomorphism or cytology mimicking papillary carcinoma or follicular neoplasm. Although LBC provided certain benefits, there was no significant difference in diagnostic accuracy between conventional smear and LBC. Immunocytochemistry was available in 38 cases (26.2%), all of which were correctly recognized as MTC. CONCLUSION: Our report summarizes how MTC is handled in contemporary Asian thyroid FNA practice. Although the detection rate of MTC by cytology alone is less satisfactory, integration with ancillary tests could achieve an excellent performance. The recognition of constitutive cytomorphologic features is needed for each cytopreparatory method, which may result in a lower threshold to initiate further workup for MTC.

Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods.

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.

PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications.

The differential diagnosis of soft tissue tumours poses a considerable challenge for pathologists, especially adipocytic tumours, as these may show considerable overlap in clinical presentation and morphological features with many other mesenchymal neoplasms. Hence, a specific and reliable marker that identifies adipocytic differentiation is much sought. We investigated the immunohistochemical expression of PIM-1 kinase in 35 samples of soft tissue tumours using tissue microarray technology and 49 full sections of adipocytic (n = 26) and non-adipocytic tumours (n = 23). Benign and malignant adipocytic tumours showed strong expression of PIM-1 while the non-adipocytic tumours were either negative or showed only weak staining for the protein. In myxoid liposarcomas, PIM-1 showed a distinct, unique vacuolar staining pattern, clearly outlining fine cytoplasmic lipid vacuoles. By contrast, non-adipocytic myxoid tumours (myxoma, chordoma and myxoid chondrosarcoma) did not show this vacuolar pattern of PIM-1 staining, although vacuolated cells were present on H&E. This differential expression was confirmed at a gene expression level in selected cases. Our results indicate that the expression of PIM-1 in adipose tissue may be a useful marker of adipocytic differentiation, in particular if the staining is both of high intensity and present in a unique, vacuolar pattern.