Nuclear Grooves Research Articles

Is Subdivision of Atypia of Undetermined Significance AUS/Follicular Lesion of Undetermined Significance Cases According to Detailed Nuclear Features Vital for Assessing the Risk of Malignancy?

Background:It has been known that the “atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)” category is the most problematic category in Bethesda system due to its highly heterogeneous morphological features. Recently, it has been reported that aspirates including nuclear atypia in the AUS/FLUS category have a higher risk of malignancy.Aims:This study aimed to assess each nuclear property in aspirates with cytological atypia and also to determine the relationship with the risk of malignancy.Material and Methods:We reviewed 980 AUS/FLUS fine-needle aspirations (FNAs) performed between '2012 and 2019' at a single institution. We classified these aspirates into four groups: AUS-N (nuclear atypia), AUS-A (architectural atypia), AUS-H (Hurthle cell change), and AUS-O (other). Nuclear features were detailed sub-classified; size and shape (enlargement, elongation, and overlapping), membrane irregularities (irregular contours, grooves, pseudoinclusion), and chromatin characteristics (pale chromatin). The estimated risk of malignancy (ROM) was calculated for each subgroup.Results:Of 980 AUS/FLUS cases, follow-up histological outcome data were available for 209 cases. Among these cases, the estimated ROM was 27.8%. The ROM were 26.4%, 15.4%, and 22.5% for AUS-N, A, and H, respectively. The most common nuclear findings associated with ROM were nuclear groove (67.9%); irregular contours (76.9%) suspected pseudoinclusion (100%) and overlapping (56%) (P < 0,001). But nuclear findings such as nuclear enlargement, mild pleomorphism, or pale chromatin have a similar ROM as architectural atypia.Conclusion:Although it is known that the presence of cytological atypia in an AUS/FLUS nodule increases the estimated risk of malignancy, all nuclear properties are not equally effective in predicting malignancy risk. Emphasizing nuclear atypia details in reports of AUS case may be a more sensitive way to identify nodules with a high risk of malignancy.

Metanephric adenoma of the right kidney: a challenging diagnosis in a 49-year-old female

Background: Metanephric adenoma of the kidney is a rare, usually solitary, and benign tumor of the kidney, predominately affecting female patients in the fifth or sixth decade of life. It is considered by some specialists to be the hyperdifferentiated benign end of the Wilm’s tumor spectrum. Case Presentation: The case was a 49-year-old woman with abdominal pain, a palpable mass in the right abdomen, and mild hematuria, without any other symptoms or laboratory findings. An ultrasonography and computed tomography revealed a tumor in the upper pole of the right kidney with a diameter of 5.3 cm. There was no infiltration of the neighboring structures and tissues. The differential diagnosis included papillary renal cell carcinoma, adult Wilm’s tumor, and metanephric adenoma. A partial nephrectomy was followed. The histological examination of the tumor revealed relatively small unvarying basophilic epithelial cells with scant cytoplasm, uniform nuclei, and some areas with nuclear grooves, delicate chromatin, and indistinct nucleoli in a loose non-cellular stroma and developed in a tightly packed alveolar, tubular, and rarely papillary pattern. The mitotic rate was extremely low. Tumor cells were positive for paired box gene 8, cluster differentiation 57, and Wilm’s tumor 1 and negative for racemase, cytokeratin 7, and EMA. The cell proliferation rate Ki-67 was extremely low, and there was diffuse, strong cytoplasmic positivity for BRAF V600E staining. Based on morphology and immunohistochemistry, the diagnosis of metanephric adenoma was made. Conclusion: Although metanephric adenomas may be difficult to diagnose clinically, the histological examination and the immunohistochemistry assay, including BRAF V600 staining, can make a safe diagnosis, avoiding the administration of incorrect treatment.

Clinical spectrum and management outcomes of Langerhans cell histiocytosis of the orbit.

Purpose:To describe the clinical spectrum and management outcomes of Langerhans cell histiocytosis (LCH) involving the orbit.Methods:Retrospective review of patients with orbital LCH presenting at the Sankara Nethralaya, Chennai, India, over the past 15 years. Demographic details, presenting features, radiology, histopathology, immunohistochemistry, and management outcomes were analyzed.Results:Nine patients were reviewed. The mean age of presentation was 10.12 ± 14.31 years (range: 6 weeks to 35 years). Eyelid swelling was the most common presenting feature (4, 44.4%), followed by proptosis (3, 33.3%). The mean duration of the presentation was 2.21 ± 2.77 months. Radiological investigations revealed orbital roof osteolytic defects in six (66.6%) patients. Six patients underwent near-complete excision of the mass while three underwent incisional biopsy. Histopathology revealed histiocytes with nuclear grooving and numerous eosinophils characteristic of LCH. The cells were positive for CD1a and S 100 antigens. None of the patients had any systemic involvement. Three received systemic steroids and four received systemic chemotherapy. At a mean follow-up of 17.85 ± 23.46 months, all had complete remission without any signs of recurrence. One patient was lost to follow-up after near-complete excision while one adult patient with a mass in the intraconal space had no recurrence after near-complete excision.Conclusion:LCH is a rare disorder of the orbit that commonly occurs in children and should be considered a differential for osteolytic lesions involving the orbit. All patients should undergo a systemic evaluation to rule out multifocal disease. The treatment depends upon disease extent and risk factors.

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

2256 A Unique Case of Concurrent Langerhans Cell Histiocytosis and Autoimmune Hepatitis Complicated by a Lower Gastrointestinal Bleed

INTRODUCTION: Autoimmune hepatitis (AIH) and Langerhans Cell Histiocytosis (LCH) are two independently rare disease processes that can have similar presentations. There have been no documented cases of concurrent AIH and LCH. We illustrate a complex case that required an interdisciplinary approach to ultimately diagnose and treat the patient. This unique presentation contributes to the medical literature of the two rare diseases. CASE DESCRIPTION/METHODS: 20-year-old male with no significant history presented with worsening jaundice, diffuse, pruritic rash, and abdominal pain over one month. On admission, the patient’s labs showed significantly elevated liver function tests (LFTs), eosinophilia, and anemia. Exam was notable for diffuse lymphadenopathy (LAD), hepatosplenomegaly, and a diffuse, non-blanching, morbilliform rash. Interdisciplinary workup was notable for positive anti smooth muscle antibody (ASMA), and anti-neutrophilic antibody (ANA). A liver biopsy was done and showed findings of severe inflammation with interface activity, consistent with AIH. A lymph node (LN) biopsy showed findings consistent with LCH, including histiocyte clusters (HC). He was started on high dose steroids with LAD/LFT improvement; yet, his hospital stay was complicated by a gastrointestinal (GI) bleed requiring a hemicolectomy. The patient was ultimately transferred to a larger referral center where he continued to improve with steroids and was ultimately discharged with close follow up. DISCUSSION: LCH tends to affect skin or bones; however, LN and GI involvement are relatively uncommon. This case was notable for a LN biopsy showing HC with reniform nuclei, nuclear grooves and eosinophils with immunohistochemical stains positive for S-100, CD1a, fascin, langerin, CD45, and CD68, consistent with LCH. The resected colon showed atypical histiocyte proliferation positive for fascin, CD4, and CD68. Key findings can help support a diagnosis of AIH, such as elevated LFTs, ASMA, and ANA, as well as a liver biopsy showing inflammation with interface activity, eosinophils, plasma cells, and characteristic fibrosis, all of which were found in this patient. In either case, steroids were indicated and ultimately helped the patient clinically improve. Such a case is distinct since the LCH appeared to be a systemic process, with findings of diffuse LAD, questionable GI involvement, and no liver involvement, but rather concurrent AIH. This case was further notable for a complication of a lower GI bleed requiring a hemicolectomy.

Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma

Abstract Objectives Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment. Methods A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC. Results Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells. Conclusion Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.

Semiquantitative assessment of cytomorphologic features can predict mutation status of thyroid nodules with indeterminate cytologic diagnosis

Molecular diagnostics increasingly direct the management of thyroid nodules with an indeterminate cytologic diagnosis. This study was undertaken to correlate cytomorphologic features with the molecular profiles in an effort to identify features predictive of molecular aberrations. One hundred eighty-nine thyroid nodules with an indeterminate thyroid cytology diagnosis (atypia of undetermined significance, suspicious for follicular lesion, and suspicious for malignancy) with an adequate sample submitted for targeted mutation detection by polymerase chain reaction or next-generation sequencing were assessed semiquantitatively for the following cytomorphologic parameters: cellularity, Hurthle cell changes, microfollicles, nuclear elongation, nuclear grooves, nuclear enlargement, nuclear atypia, extent of atypia, and colloid. Based on this evaluation, a cumulative cytomorphologic score (CCS) and a more simplified overall atypia score (OAS) were assigned to each case. Associations among mutational status and each of the aforementioned parameters, CCS, and OAS were determined. Of the 189 nodules with indeterminate cytology, 63 (33.3%) harbored at least 1 mutation. RAS and BRAF were the most common mutations, found in 34 (18.0%) and 13 (6.9%) cases, respectively. Both CCS and OAS were highly associated with the presence of all mutations (P < .0001) and with the presence of BRAF and RAS mutations in particular (all P < .01). Semiquantitative assessment of various cytomorphologic features in indeterminate thyroid cytology cases showed a strong association of higher OAS and CCS and incidence of BRAF and RAS mutations. Using a more objective approach to thyroid cytology can potentially decrease the overall number of indeterminate diagnoses, leading to fewer repeat procedures and unnecessary surgical procedures.

GLIS rearrangements in thyroid nodules: A key to preoperative diagnosis of hyalinizing trabecular tumor.

Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with peculiar morphologic features that overlap with those of papillary thyroid carcinoma (PTC). Specifically, the presence of enlarged oval nuclei, nuclear grooves, and intranuclear pseudoinclusions makes precise cytopathologic diagnosis challenging. If the cytopathologic diagnosis is suspicious for malignancy (Bethesda V) or is malignant (Bethesda VI), a total thyroidectomy, which would be considered an overtreatment, may follow. The recent discovery of the strong association between GLIS fusions and HTT sheds light on its pathogenesis and offers a pathway for its presurgical identification. Although the number of cases analyzed is limited, the recent landmark study shows that GLIS fusions are highly specific for HTT and that lobectomy is the likely appropriate surgical treatment, because these neoplasms, which lack invasion, are benign. For overall success, cytopathologic recognition of the subtle features is important to avoid false-positive diagnoses and directing potential HTT cases toward indeterminate cytopathologic diagnoses, which would trigger further molecular testing. Additional studies are needed to determine whether a malignant counterpart of GLIS fusion-positive HTT exists and if more conservative approaches may be taken.

Cytologic features of upper gynecologic tract adenocarcinomas exhibiting mesonephric-like differentiation.

Mesonephric adenocarcinomas are rare neoplasms whichmost commonlyarise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and molecular characteristics recently have been described in the uterine corpus and ovary. Herein, the authors sought to characterize the cytomorphologic features of adenocarcinomas exhibiting mesonephric-like differentiation arising in the upper gynecologic tract. Institutional databases were queried retrospectively for tumors of the upper gynecologic tract described as a "tumor of Wolffian origin" or "with mesonephric features" between 2007 and 2017. All available cytologic material was reviewed. Cytomorphologic characteristics wereevaluated by 3 pathologists. The current study cohort consisted of 8 cases taken from 7 patients. Primary sites included the ovary (3 cases); endometrium (4 cases); and pelvis, not otherwise specified (1 case). All cases demonstrated tight 3-dimensional clusters of overlapping cells. Additional architectural features included tubular (5 of 8 cases; 63%) and papillary (3 of 8 cases; 38%) formations. Cells were small with scant (7 of 8 cases; 88%) to moderate (1 of 8 cases; 12%) cytoplasm. Three of the 8 cases (38%) demonstrated extracellular hyaline globules. Nuclei were uniform in size (6 of 8 cases; 75%) or showed mild anisonucleosis (2 of 8 cases; 25%). Nuclear grooves and indentations were observed in all cases. Mitoses (5 of 8 cases; 63%) and apoptotic bodies (4 of 8 cases; 50%), when present, were rare. No necrosis was noted. Adenocarcinomas exhibiting mesonephric-like differentiation show a monotonous population of small cells with scant to moderate cytoplasm and abundant nuclear grooves arranged in tight, overlapping, 3-dimensional clusters. Occasionally, papillary or tubular architecture, as well as extracellular hyaline globules,may be seen. These features should prompt further testing (eg, immunohistochemistry) to confirm the diagnosis and to exclude potential mimics.

Disseminated Langerhans cell histiocytosis presenting as oesophageal disease in a cat

Case summaryAn 11-year-old female spayed domestic shorthair cat was referred with a 2-month history of ptyalism, hyporexia and weight loss. Physical examination revealed reduced body condition score (2/9) and decreased skin turgor. Laboratory abnormalities included mild erythrocytosis, elevated creatine kinase, hypercobalaminaemia and hypofolataemia. CT of the head and abdominal ultrasonography were within normal limits. Gastroesophagoscopy revealed mucosal ulceration and possible stenosis of the distal oesophagus. Thoracic radiographs and iodine oesophagram showed a soft tissue opacity in the caudodorsal thorax compatible with a parietal oesophageal mass causing luminal stenosis or an extra-parietal mass causing ventral displacement and compression of the oesophagus. Pulmonary nodules were observed in the cranial lung lobes. CT of the thorax confirmed the oesophageal origin of the mass and the presence of pulmonary nodules scattered throughout the lung parenchyma. The patient was euthanased given the imaging findings and perceived guarded prognosis. Post-mortem examination revealed multifocal nodular lesions affecting the oesophagus, lungs, kidneys and pancreas. Histopathological examination identified atypical round cells characterised by eosinophilic cytoplasm and pale nuclei with prominent nuclear grooves, compatible with neoplastic histiocytic cells. Immunohistochemistry revealed strong expression for CD18, Iba-1 and vimentin. Transmission electron microscopy demonstrated intracytoplasmic organelles consistent with Birkbeck granules of Langerhans cell origin in lesional histiocytes. These findings were compatible with a diagnosis of disseminated Langerhans cell histiocytosis.Relevance and novel informationTo our knowledge, this is the first report of disseminated Langerhans cell histiocytosis with oesophageal involvement in a cat.

Diagnosing atypia of undetermined significance in thyroid fine needle aspiration samples using nuclear scoring

BackgroundAtypia of undetermined significance (AUS) is an indeterminate category in the Bethesda system for reporting thyroid cytopathology. Cytological features described as atypia are not always observed in every case, and it is difficult to determine how the small population of cells with enlarged nuclei, a few grooves, and rare elongated nuclei should be classified. Therefore, there is inter-intra observer variability considering these cell types, even though the cytological criteria are well defined. Therefore, this study aimed to establish a nuclear scoring system to help in the differential diagnosis of AUS. MethodsFine needle aspiration (FNA) samples that showed AUS and had surgical follow-up were included in this study. The aspirate was scored for the presence of intanuclear cytoplasmic inclusions, nuclear grooves, overlapping, enlargement, and elongation individually. The total nuclear score for each case was calculated. Statistical analysis of the association between each nuclear feature and the presence of papillary thyroid cancer (PTC) in the surgical specimens was performed. Cut-off points from the total score of these nuclear features were also calculated. ResultsNuclear grooves and overlapping were more common in malignant cases (p < 0.001 and p = 0.048, respectively). A cut-off point of ≥5.5 for the total score was sensitive and specific for defining malignancy. ConclusionThe risk of PTC was higher in nodules with more prominent nuclear overlapping or nuclear groove in their FNA samples. In order to achieve a more confident AUS diagnosis, our scoring system can be helpful for thyroid FNA samples.

Metastatic low-grade endometrial stromal sarcoma of uterus presenting as a primary pancreatic tumor: case presentation and literature review

BackgroundMetastatic tumors to the pancreas are uncommon, accounting for approximately 2% of pancreatic malignancies. The most common primary tumors to give rise to pancreatic metastases are carcinomas.Case presentationA 50-year old female patient was investigated for a cause of abdominal discomfort. She had a 2-year history of menorrhagia and dysmenorrhea which was ascribed to a fibroid uterus. On imaging, she was found to have a large solid and cystic mass in the tail of the pancreas. Imaging also confirmed a fibroid uterus. A distal pancreatectomy and splenectomy showed a 9 cm circumscribed mass within, and grossly confined to, the parenchyma of the pancreatic tail.Microscopically, the pancreatic lesion was lobulated, and well-circumscribed, but focally infiltrative. It comprised sheets of uniform spindled to epithelioid cells with round to oval nuclei, coarse to vesicular chromatin, visible nucleoli, nuclear grooves and clear to eosinophilic cytoplasm. Prominent arterioles were identified. The stroma was collagenized in areas. Occasional hemosiderin-laden macrophages were seen, and focal cystic change was present. There was no evidence of nuclear pleomorphism, mitotic activity or necrosis, and there was no evidence of endometriosis despite multiple sections being taken. Immunohistochemistry showed that the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), Wilms tumor-1 (WT-1) and smooth muscle actin (SMA). RNA sequencing detected a PHF1 rearrangement.The morphological, immunohistochemical and molecular features were of a low-grade endometrial stromal sarcoma (LG-ESS). Subsequent total hysterectomy and bilateral salpingo-oophorectomy 3 months later, showed uterine fibroids and a 5 cm low-grade endometrial stromal sarcoma confined to the uterus, with lymphatic invasion.ConclusionsTo the best of our knowledge, this is the first documented case of metastatic endometrial stromal sarcoma of uterus presenting as a primary pancreatic neoplasm. An unexpected extra-uterine location and unusual presentation of ESS may make the diagnosis challenging, despite classic histological features. Morphological, immunohistochemical and molecular findings must be combined to render the correct diagnosis.

SUN-601 Papillary Thyroid-like Carcinoma Of The Kidney

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy and usually associated with good prognosis. Typical sites for metastases include lymph nodes, lung and bone, while renal metastasis is rare. Here we present a case of primary papillary thyroid-like carcinoma of the kidney. Histologically and immunohistochemically, the tumor closely resembled PTC, but no abnormalities were found in the thyroid or cervical lymph nodes. CASE REPORT: 54-year-old Caucasian male non-smoker with history of GERD, and dyslipidemia was referred to ENT for evaluation of left tonsillar mass. PET CT showed hypermetabolic regions in the left base of tongue and lingual tonsil, and hypodensity in the lower pole of the left kidney. He underwent bilateral palatine tonsillectomy for invasive squamous cell carcinoma followed by adjuvant chemoradiation. MRI of the abdomen confirmed a 1.7cm left lower pole renal mass and he underwent laparoscopic partial nephrectomy. Pathological examination of the renal tumor was suggestive of papillary carcinoma of thyroid origin (immunohistochemical staining positive for TTF-1, PAX-8 and CK7, and negative for thyroglobulin, RCC, CK20 and racemase). Histologically, the tumor displayed nuclear inclusions, nuclear grooves and papillary architecture. RET oncogene amplification further supported the diagnosis of PTC. Neck ultrasound was negative for thyroid nodules or lymphadenopathy, and no residual hypermetabolic disease was seen on follow-up PET CT. Due to concern for metastatic PTC, the patient underwent total thyroidectomy with central lymph node dissection. Pathology showed only benign thyroid with lymphocytic thyroiditis. Post-thyroidectomy whole body scan showed no abnormal radiotracer uptake to suggest residual thyroid or disease. Serum thyroglobulin level remained undetectable with negative anti-TPO antibodies. DISCUSSION: This patient presented with an incidentally discovered renal tumor that histologically and immunohistochemically resembled PTC. Renal metastasis of PTC is very rare, with less than 20 cases reported, yet positive staining for TTF-1 is highly sensitive and specific for thyroid cells. The possible origins of the tumor include metastasis from an occult intra-thyroidal tumor, primary PTC that had undergone spontaneous resolution, or a primary renal tumor with thyroid-like characteristics. To our knowledge this is the second reported case of a primary papillary thyroid-like cancer of kidney.

MON-628 Noninvasive Encapsulated Papillary RAS-Like Thyroid Tumor (NEPRAS) as a Possible Novel Subtype of Borderline Tumor

Background: A subset of thyroid tumors was classified into borderline/precursor tumors in the latest World Health Organization (WHO) classification. However, these tumors were defined only in terms of follicular structure, including hyalinizing trabecular tumor (HTT), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and uncertain malignant potential (UMP). As papillary microcarcinoma was proposed to be renamed to papillary microtumor (PMiT), there would be no reasons for restricting borderline/precursor tumors to the follicular growth pattern. Clinical Case: A 26-year-old man was incidentally found to have a 23 mm nodule in his thyroid. After undergoing left lobectomy, histological findings revealed extremely delicate nuclear changes in a noninvasive encapsulated papillary growth-patterned tumor. Tumor cells showed nuclear enlargement, irregularity, elongation, and overlapping as well as a few nuclear grooves. Nuclear pseudoinclusions were absent and chromatin characteristics were insufficient (nuclear score 2 according to Nikiforov et al. (1)). The patient was diagnosed with an encapsulated conventional papillary thyroid carcinoma by a local pathologist; however, a second-opinion consultation endorsed a follicular adenoma with papillary hyperplasia. In a third-opinion consultation, immunohistochemical analyses revealed a low MIB-1 labeling index and negative staining for cytokeratin 19 and BRAFV600E, which supported the expected indolent clinical behavior. Remarkably, mutational analysis identified a heterozygous point mutation of the KRAS gene but not the BRAF genes. Eventually, we speculated that this tumor could be a possible example of a novel borderline tumor with a papillary architecture, which does not qualify as NIFTP or UMP under the current WHO criteria. The patient refused additional surgery (complete thyroidectomy), and developed no recurrence or distant metastasis for 24 months. Conclusion: We reported a significant observer variation in a noninvasive encapsulated papillary growth-patterned tumor with delicate nuclear changes and a KRAS mutation. We speculated that our case could be an example of a novel borderline tumor with a papillary structure. Further studies using a larger number of patients are needed to elucidate this disease entity, because the possible introduction of terminology such as “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” could relieve psychological burdens of the patients similar to NIFTP. Reference: (1) Nikiforov YE, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. 2016;2:1023-9.

Clinicopathological and molecular features of Erdheim-Chester disease accompanied with Langerhans cell histiocytosis

Objective: To investigate the clinicpathological and molecular features of Erdheim-Chester disease (ECD) as well langerhans cell histiocytosis (LCH). Methods: The clinical, histopathological, molecular findings, immunophenotype, treatment and prognosis in 4 cases of ECD combined LCH were evaluated from February 2015 to September 2018 with review of the relevant literature. Results: 2 cases were male, and 2 were female, aged from 7-55 years. Microscopically, there were two different areas, in the first area, the lesions were composed of foamy histiocytes, spindle-shaped fibroblasts, scattered multinucleated giant cells. Lymphocytes, plasma cells, and giant cells were also found. In the other, the lesions were composed of histiocytes with obvious nuclear groove, associated with a variable number of eosinophils, lymphocytes and plasma cells. Immunephenotype, In the second area, histiocytes were positive for CD1a (4/4), S-100 (4/4),CD207/Langerin (4/4), cyclin D1(4/4), and in the two different area, the histiocytes were positive for CD68, CD163, Braf. Ki-67 positive index 1%-10% BRAF V600E gene mutation was detected in three cases. Conclusion: ECD combined LCH was a very rare histiocytosis tumor and its correct diagnosis relies on histopathologic features, immunohistochemical staining, and BRAF V600E gene detection.

Relationship between genetic alterations and clinicopathological characteristics of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is characterized by proliferation of follicular cells with distinctive nuclear features such as ground glass appearance, nuclear groove and pseudoinclusion. From the proliferation pattern, PTC is divided into several histological subtypes; conventional histology is classified as papillary type, and there are also follicular and solid variants. PTC is heterogeneous in genetic alterations. PTC with BRAF mutation presents a histology of conventional PTC, and follows an aggressive clinical course. Most cases of PTC with RAS mutation show a follicular variant, and prognosis is favorable. RET/PTC1 is observed sporadically and in young cases, and prognosis is favorable. RET/PTC3 is associated with radiation exposure, and the solid variant is frequent. ETV6-NTRK3 may be associated with radiation exposure, and the clinical course is aggressive. Mutation in the telomerase reverse transcriptase promoter is observed in PTC cases involving elderly male patients. Tumor size is large, associated with distant metastasis and advanced stage. This mutation is found concomitantly with BRAF mutation, and the clinical course is aggressive. Genetic alterations form subsets of PTC with distinct clinicopathological features. Careful assessment of clinicopathological features is considered useful in predicting clinical course and when planning treatment.

Utility of cytomorphology in distinguishing solid pseudopapillary neoplasm of pancreas from pancreatic neuroendocrine tumor with emphasis on nuclear folds and nuclear grooves.

Pancreatic solid pseudopapillary tumor (SPN) and pancreatic neuroendocrine tumors (Pan-NET) have close resemblance on imaging and cytomorphology, though they differ in their prognosis and treatment strategy. SPNs are low-grade indolent tumors while Pan-NETs harbor malignant potential with propensity to metastasize. We aim to differentiate SPN from Pan-NET based on cyto-morphology; to classify nuclear membrane (NM) irregularities or nuclear folds into four grades and see whether they bear any difference with respect to the two entities. Eighteen and ten confirmed cases of SPN and Pan-NET were included in the study. Smears were assessed for architecture, background changes, cellular, and nuclear features, which were compared between the two study groups. Nuclear folds were classified into four grades. Nuclear folds and nuclear grooves were also compared between the two groups. All SPN patients were females; mean age of 28 years. Pan-NET patients had equal male to female ratio; mean age of 46 years. Both SPN (78%) and Pan-NET (71%) showed predilection for pancreatic head. Mean size of lesion was 4.8 cm and 3.1 cm in SPN and Pan-NET groups. Papillary pattern, branching capillaries, degenerative background were significantly more prominent in SPN; sudden anisonucleosis and cytoplasmic granularity in Pan-NET. Metachromatic matrix, hyaline globules, and nuclear grooves were noted exclusively in SPNs. Nuclear fold grades 2 and 3 were more characteristic of SPN than Pan-NET (P = 0.041 and 0.002, respectively). Cytomorphology is vital in differentiating SPN from Pan-NET with nuclear folds being an important nuclear feature.

Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid-based cytology.

The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

Qualitative and quantitative cytomorphological features of primary anaplastic lymphoma kinase-positive lung cancer.

Anaplastic lymphoma kinase (ALK) positive (+) lung cancers are predictive for response to crizotinib and alectinib. There are many cases of lung cancer in which surgery cannot be performed, and such cases require diagnosis by cytological specimen or biopsy. Estimating ALK (+) lung cancer from cytomorphology would allow molecular testing to proceed without the waste of a small amount of specimen. The purpose of this study was to assess whether qualitative and quantitative cytomorphological features are sufficient for distinguishing primary ALK (+) from ALK (-) lung cancer. We examined eight qualitative cytomorphological parameters and three quantitative nuclear morphometric parameters in 17 cases of primary ALK (+) lung cancer, diagnosed by fluorescence insitu hybridisation (FISH) using histological specimens, and in 41 cases of ALK (-) lung cancer. Quantitative nuclear morphometric parameters were analysed by a computer-assisted image analysis system. In ALK (+) lung cancer, three qualitative parameters (signet ring cells, nuclear grooves and single type nucleoli) and two quantitative parameters (large nuclear area and irregular nuclear shape) were observed in significantly higher proportions. However, in ALK (-) lung cancer, one qualitative parameter (unclear and multiple type nucleoli) was seen significantly more often. These results show that the cytomorphological features of signet ring cells, nuclear grooves and nucleoli shape can help to triage a small amount of cytological and biopsy specimens for appropriate molecular testing of primary ALK (+) lung cancer.

Role of nuclear grooves in the cytological diagnosis of papillary carcinoma thyroid

Introduction: It is well known that nuclear grooves play a major role in the diagnosis of papillary carcinoma thyroid (PCT). Furthermore, grooves are found in many nonneoplastic lesions of thyroid. Aims: The aim of this study is to calculate the percentage of nuclear grooves in histopathologically proven cases of papillary carcinoma and nonneoplastic lesions (Hashimoto's thyroiditis and colloid goiter). Materials and Methods: This retrospective study was carried out by reviewing the data and cytology smears of 21 histopathologically confirmed cases of PCT and 10 cases each of Hashimoto's thyroiditis and colloid goiter. The percentage of nuclear grooves was calculated in oil immersion by counting 100–500 cells depending on the cellularity. Results: The percentage of nuclear grooving ranged from 15% to 85% in the papillary carcinoma cases. Greater than 20% nuclear grooves were observed in 19 (90.4%) of the cases. Nuclear crowding and overlapping, pale chromatin, nuclear grooves, nuclear enlargement, and prominent nucleoli were seen in all (100%) cases. Intranuclear cytoplasmic pseudoinclusions were seen in only 5 (23.8%) of the cases. Histiocytes, metaplastic cells, and multinucleated giant cells were seen in 12 (57.1%), 10 (47.6%), and 6 (28.5%) of the cases. The percentage of nuclear grooves in nonneoplastic cases overall observed was Conclusion: Whenever in doubt, a diagnosis of papillary carcinoma can be offered confidently by this semiquantitative approach for grooves in combination with other features.