Cytologic Appearance Research Articles

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

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. 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. 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. 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.

Grade I, II and III Follicular Lymphomas Express Ig VH Genes with Different Patterns of Somatic Mutation

Follicular lymphoma (FL) is an indolent, B-cell, non-Hodgkin’s lymphoma with varying cytological appearance and clinical behavior. The genetic hallmark of FL is the t(14;18) translocation, and as a germinal center derived entity it is also characterized by somatic hypermutation of the immunoglobulin heavy chain (IgH) gene. In an attempt to correlate this molecular signature with the cytological grading of FL, we have analyzed the IgH variable (IgVH), regions in all cytological grades of FL. Four FL cases showing t(14;18) translocation were classified into grade I-III categories according to the current WHO guidelines. The IgVH gene segments were PCR-amplified, sequenced, and compared to their respective germline IgVH sequences. The neoplastic cells of grade I and II FLs revealed clonally related, but highly divergent IgVH gene sequences indicating the ongoing nature of somatic hypermutation. Grade III FL also showed extensive presence of somatic hypermutation, but these mutations were not associated with intraclonal divergence. Thus, these results suggest that grade I-II and grade III FL may represent different biological entities. The presence of ongoing somatic hypermutation of IgVH sequences in grade I and II FLs is compatible with direct follicular origin of these tumor cells, contrasting the homogenous, stable clones of grade III FL resembling a post-follicular stage of B-cell development. Our findings demonstrate that contrary to the three tiered cytological grading, molecular features of IgH genes classify FL into two distinct subcategories. These studies also suggest that with progression FL gains post-follicular–like molecular features and becomes independent of the germinal center microenvironment.

Nodular Fasciitis: A Tumor withMisnomer!

Nodular fasciitis is a peculiar a tumor in its clinical presentation and cytological appearance, owing to its similarity with soft tissue sarcoma. It is a rare benign neoplasm most commonly occurring in the upper extremity. Meanwhile it is selflimitingreactiveprocessmimickingmalignantlesioncomposedofFibroblastsandMyoblasts.Herewearereportingtwocases in the hand, with varied clinical presentation, were treated with complete surgical excision and pathologically confirmed to be NodularFasciitis. The term Nodular Fasciitis although pathologically isindicative of an inflammatory process, clinically itseemsto be misleading since “Fasciitis” usually denotes an acute serioussoft tissue infection. As perliterature, this benign tumoris often described as pseudo-sarcomatous, yet itstitle gives no hint ofsuch a concern. After dealingwith the presented cases and the literature reviewit is evident that, diagnosing thisspecific lesion on basis of clinical picture, MRI orfine needle aspiration is very unlikely. Most cases will end up having surgical excision due to itsfrequently alarming presentation.

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix: A Study on Morphologic Diversity.

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.

A prospective study on clinicopathological study of cervical lymphadenopathy

Cervical lymphadenopathy is a common clinical presentation in various departments of clinical practice. This study was done to know the correlation between clinical presentation of FNAC and histopathology of cervical lymphadenopathy, to emphasize the role of fine needle aspiration cytology (FNAC) in etiologic workup in cervical lymphadenopathy. 50 patients with cervical lymphadenopathy were assessed clinically, by laboratory and by FNAC study over a period of two years. In the present study, results revealed that tuberculous lymphadenopathy is the commonest cause of cervical lymphadenopathy with 68% followed by chronic non-specific lymphadenopathy with 32. Of the 35 patients whose fine needle aspiration cytology (FNAC) showed granulomatous changes, 50 had subsequent surgery and histological confirmation of the cytological appearance. 34 had TBLN (Tuberculous Lymphadenopathy), thus the specificity of FNAC was 94 per cent in diagnosing tuberculosis related granulomatous lymphadenopathy. One false positive FNAC was reported histologically to be non specificity. Present study had cervical lymph node swelling. Other common presenting symptoms were loss of weight and loss of appetite (20%), fever (30%), axillary and inguinal swellings (4%), cold abscesses (8%), pain (6%), sore throat, cough, discharging sinus, old sinus scars, caries tooth (2%). there was only unilateral involvement of node in 72% of cases right side was affected in 32% and left side was affected in 40% of cases bilateral involvement was seen in 14% of the cases. The lymph nodes were associated with other groups of lymph nodes in 10% of cases. In our study the sensitivity and specificity of FNAC of tuberculous cervical lymphadenopathy is 77 and 94 respectively. The results concluded that tuberculosis is the most common cause of cervical lymphadenopathy in the Indian population followed by reactive lymphadenitis and metastatic deposits. Reactive lymphadenitis is the commonest cause of cervical lymph node enlargement in different age group, infective in 11-40 yrs. age group including tuberculous and suppurative lymphadenitis, neoplastic lesions in more than 40 age group including metastatic disease and nonhodgkins lymphomas. FNAC is an important diagnostic modality for the etiologic workup in significant cervical lymphadenopathy and is almost as sensitive and specific as excision lymph node biopsy when an adequate aspirate is examined by expert eyes.

Desmoplastic Small Round Cell Tumors With Atypical Presentations: A Report of 34 Cases.

Desmoplastic small round cell tumor (DSRCT) is an aggressive round cell sarcoma that arises in the abdominal cavity/pelvis of young males. We sought to expand its clinicopathologic spectrum. Cases of DSRCT presenting in patients >30 years of age or tumors arising outside of the abdominal cavity/pelvis were retrieved. Thirty-four cases were identified. Sixteen tumors arose at atypical sites (head/neck, intracranial, thigh, axilla/shoulder, inguinal/paratesticular, intraosseous, and uterine corpus). The remaining 18 patients were older than 30 years, and their tumors involved the abdomen or pelvis. The majority of cases showed areas with classic histology, while 6 cases exhibited solid growth and 5 showed macronodular architecture. Cytologic appearance included round cell, rhabdoid, epithelioid, and small cell. DSRCT may arise at nonabdominal locations in both pediatric and adult populations, as well as intra-abdominally in older adults, and these tumors exhibit high rates of metastasis and morbidity.

Uterine pleomorphic leiomyosarcoma with osteoclastic giant cells: Case report with peritoneal washing cytology and cell block study

Uterine leiomyosarcoma (LMS) with osteoclastic giant cells (OGCs) is extremely rare. However, its morphological appearance and aggressive behavior may have resulted in its being diagnosed as so-called giant cell malignant fibrous histiocytoma (MFH) in the past. Effusions are not uncommon in LMS and may be indicative of an unfavorable prognosis. We report a case with the cytological appearance of a uterine LMS with OGCs metastatic to lower pelvic peritoneum. The pelvic washing specimen consisted of three-dimensional aggregates of atypical cells. The cytohistologic and immunohistochemical study obtained from the cell block and the tumor mass showed overlapping features such as bizarre pleomorphic spindle cells containing numerous evenly dispersed OGCs. The malignant tumor cells showed extensive positivity for desmin, h-caldesmon and multifocal positivity for smooth muscle actin (SMA) whereas OGCs stained with CD68. We stress the usefulness of performing cell block and subsequent immunohistochemistry in order to make an accurate cytohistologic correlation.

HPV-related Oropharyngeal Carcinoma: A Review of Clinical and Pathologic Features With Emphasis on Updates in Clinical and Pathologic Staging.

There has been a sharp increase in the incidence of the human papilloma virus-related oropharyngeal squamous cell carcinoma, partly due to the increasingly widespread awareness and recognition of this entity. This review assimilates the recent histopathologic classifications, staging systems, rapidly expanding research base and developments in management of human papilloma virus-related oropharyngeal squamous cell carcinoma and summarizes their implications for routine diagnostic practice. Differential diagnoses and their cytologic appearances are detailed and the utility of p16 staining and other immunohistochemistry testing is discussed.

Thyroid FNA biopsies comprised of abundant, mature squamous cells can be reported as benign: A cytologic study of 18 patients with clinical correlation.

A thyroid nodule comprised almost exclusively of mature, benign-appearing squamous cells is an uncommon finding in fine-needle aspiration (FNA) biopsies of thyroid nodules. Reporting such specimens was not originally addressed by The Bethesda System for Reporting Thyroid Cytopathology. The authors correlated the biologic behavior of the specimens with their benign cytologic appearance through clinical, radiographic, and surgical follow-up. The pathology archives of 3 tertiary hospitals were searched for thyroid FNA specimens consisting of mature squamous cells without atypia. The authors reviewed all available slides and included only cases that were moderately to highly cellular; nucleated or anucleate squamous cells without atypia comprised the vast majority of the cellularity. Available clinical information and/or thyroid ultrasound examination(s) were reviewed by an endocrinologist or radiologist, respectively. A total of 18 patients (7 men and 11 women; age range, 19-76 years) with 20 nodules met the prespecified inclusion criteria. The average nodule size was 2.1 cm. Common sonographic characteristics included a well-defined appearance, the lack of internal vascularity, a thin outer wall, general hypoechogenicity with low-intermediate internal echoes, and posterior acoustic enhancement. Clinical and radiographic follow-up (mean, 3.8 years; range, <1 to 9 years) was available for 9 patients, and all nodules were stable. All 4 cases with histologic follow-up were benign squamous-lined cysts. The findings of the current study suggest that thyroid FNA specimens comprised almost exclusively of mature squamous cells can be reported as benign. Cancer Cytopathol 2018;126:336-41. © 2018 American Cancer Society.

Cosmetic facial fillers: A cytological trap for the unwary

We present the case of a 49-year-old female with a swelling of the left cheek who had an FNA performed in 2016 which showed abundant mucinous material and blood. A differential diagnosis of mucocele or mucinous lesion was offered and recommendation that an excision be performed. A further FNA was performed 18 months later with the clinical details of ? Aquamid. Cytological appearances were consistent with the published papers documenting the appearance of Aquamid. This is a popular facial filler and may be a trap for the unwary.

Correlative Study of Cytological Features in Grading of Invasive Breast Carcinoma.

Context:Fine-needle aspiration cytology (FNAC) is a proven diagnostic technique for establishing the benign or malignant character of breast lesions. Several cytological grading systems have been proposed for grading of carcinoma breast, with results similar to histologic grades.Aims:This study sought to evaluate the prognostic value of FNAC in invasive ductal carcinoma of breast by correlating it with histological grade.Settings and Design:Tertiary care hospital, retrospective analytical study.Patients and Methods:One hundred and fifty cases of breast carcinoma that underwent modified radical mastectomy consequent to an FNAC diagnosis were included in the study. Robinson's grading system and Elston–Ellis modification of Scarff–Bloom–Richardson grading system were used to assign cytologic and histologic grades, respectively.Statistical Analysis:The cytological grades were correlated with the histological grades using χ2-test and Spearman's rank correlation coefficient. The individual features of the cytological grades were correlated with the histological grades using Kappa coefficient and χ2-test. Values were considered significant at P < 0.05.Results:A statistically significant association was observed between cytologic and histologic grades (r = 0.97; P < 0.01) with sensitivity and specificity, respectively, of 100% and 93.95% for cytological grade 1, 100% and 100% for cytological grade 2 and 100% and 100% for cytological grade 3. Also, a positive correlation was found between each feature of the cytologic grade and the histologic grade (P < 0.05). Among these, a better correlation was demonstrated by cytological features like cell uniformity (Kappa coefficient = 0.50) and appearance of nucleoli (Kappa coefficient = 0.52).Conclusions:Robinson's cytologic grading system is a reliable grading method on FNAC smears of cases of carcinoma breast. It correlates well with Elston–Ellis modification of Scarff–Bloom–Richardson grade in invasive ductal carcinoma of breast.

Large nested variant of urothelial carcinoma: aclinicopathological study of 36 cases.

The large nested variant of urothelial carcinoma (LNUC) has been added to the World Health Organization (WHO) 2016 classification. Scant data exist, and little is known about its clinical behaviour. Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with cytokeratin (CK)7, p63, GATA-3, CK20, p53 and Ki-67 was performed. Included were 26 cystectomies (RC) and 10 resections (TURB) belonging to 36 patients with an average age of 66.7years. Fourteen (39%) were pure LNUCs, and 22 (61%) displayed mixed features. Seventy per cent of the TURBs had pT2 tumours, while 58% of RCs had extravesical disease (≥pT3 and/or ≥pN1), with the rate of advanced disease being higher in mixed (69%) in comparison to pure cases (40%). Similarly, 38% of mixed cases had nodal metastases in comparison to 20% of pure cases. Overall, eight patients (24%) died of disease at a mean interval time of 21.7months and seven patients (21%) showed recurrence or metastases. Disease progression was significantly higher in mixed cases (55 and 31% in mixed and pure cases, respectively). Positive staining was: CK7=87.5%, CK20=72%, GATA-3=91%, P63=100%, p53=56% and Ki-67=mean of 16%. Despite the bland cytological appearance and deceptive pattern of invasion of the LNUC, our study validates its fully malignant potential with metastatic spread and tumour-related deaths. Distinguishing mixed from pure LNUCs seems to be of value. LNUCs show comparable immunophenotype to both conventional urothelial carcinoma and the nested variant of urothelial carcinoma.

Aneurysmal fibrous histiocytoma – spindle cell tumour with pigment: A diagnostic dilemma on cytology

This article discusses the possibility of making a confident diagnosis of aneurysmal fibrous histiocytoma on the basis of its cytological appearance.

High-grade squamous intraepithelial lesion (HSIL) of the cervix with bizarre cytological appearances (‘pleomorphic HSIL’): a review of 19 cases

Cervical high-grade squamous intraepithelial lesions (HSILs) are typically characterised by a proliferation of immature basaloid cells with relatively uniform hyperchromatic nuclei. In this report we describe 19 cases of HSIL exhibiting focal but very marked nuclear atypia often associated with multinucleation ('pleomorphic HSIL'). The bizarre cytological changes mainly involved the basal epithelium particularly in endocervical crypts where the neoplastic cells undermined the native glandular epithelial cells. Superficially invasive squamous cell carcinoma (SISCCA) was present in three cases (16%) and while this was more common than in a comparative series of 40 'conventional' HSIL excision specimens (5%), the difference was not statistically significant. All three invasive cases demonstrated additional histological features that have been associated with increased risk of SISCAA (expansile crypt involvement by HSIL, luminal necrosis, and/or intraepithelial squamous maturation), and the invasive foci were associated microanatomically with conventional-type rather than pleomorphic HSIL. The bizarre cells expressed p16 and p63 proteins but usually lacked mitotic activity and showed less Ki-67 labelling than adjacent conventional HSIL. These findings suggest that pleomorphic epithelial changes in HSIL do not necessarily indicate more aggressive biological behaviour and may, in some cases, represent a degenerative phenomenon.

An inter-correlative study on clinico-pathological profile and different predisposing factors of oral leukoplakia among the ethnics of Darjeeling, India

Context: Idiopathic leukoplakia is the most common potentially malignant disorder of oral cavity. Owing to the year-wide cold environment in Darjeeling, here the indigenous ethnic people practice a distinct addiction pattern that strongly predisposes them to oral leukoplakia. Aims: The purpose of the present study was to assess the clinico-pathological profile and various predisposing factors involved in oral leukoplakia, and to correlate its exfoliative cytological appearances with the histopathological diagnoses. Materials and Methods: A total of 53 patients were clinically diagnosed with oral leukoplakia during the study period. All information − clinical data pertaining to the patient and the patch, their personal history including addiction and diet, and the cyto-histopathological features of the lesion − was evaluated and methodically compared with each other using the statistical software, Statistical Package for the Social Sciences version 16.0. Results: The female-dominated cohort was chiefly affected with thin leukoplakia (67.9%) involving their buccal mucosa (66.1%). Smokeless tobacco (49.1%) was the most popular addiction. Alcoholism and smoking, increasing daily frequency of tobacco misuse, and verrucous and granular leukoplakias were significantly associated with dysplastic transformation (P

Improving Bethesda Reporting in Thyroid Cytology: A Team Effort Goes a Long Way and Still Miles to Go….

Context:Fine-needle aspiration cytology is the first step in evaluation of thyroid nodules. Although the Bethesda classification for reporting thyroid cytology has been purported that this uniformity in reporting cytology thereby facilitating clinical decision-making, there are also studies indicating that the reporting percentage and the rates of malignancy in each category vary considerably from center to center making the clinical decision more difficult.Aim and Materials and Methods:We looked at our retrospective cytology and histopathology data of thyroid nodules operated between 2012 and 2014 and then prospectively collected data during 2015–2016. In the prospective arm, for every thyroid nodule that was sampled, there was a discussion between the endocrinologist and the cytopathologist on the risk of thyroid cancer (based on the patient's history, examination findings, sonographic pattern, and the cytological appearance).Results:We noted that there was considerable improvement in reporting standards with the rates of nondiagnostic cytology dropping from 11% to 5%, an increased reporting of Bethesda Category 2 and 6 which are the definitive strata of benign and malignant nodules (38% to 41% in Category 2 and 7% to 11% in Category 6) with a high specificity (100%). There was a decline in numbers of Category 4 and 5 (13% to 9% in Category 4 and 12% to 3% in Category 5). The reporting prevalence of Category 3 increased from 19% to 27%.Conclusions:We conclude that a team approach between the clinician who performs the ultrasound and the reporting cytopathologist improves Bethesda reporting, its predictive value, and thus potentially avoiding unnecessary thyroidectomies in benign thyroid nodules and hemithyroidectomies in thyroid cancers.

Ang-1 and Ang-2 expression in angiomyolipoma and PEComa family tumors

ObjectivePerivascular epithelioid cell tumors (PEComa) are an uncommon family of soft tissue tumors. Previously, we described that the presence of pericyte antigens among PEComa family tumors differs extensively by histologic appearance. MethodsHere, we extend our findings using the pericyte antigens Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2), using immunohistochemical detection in human tumor samples. ResultsWhile Ang-1 showed no expression across any PEComa family tumor, Ang-2 showed expression that like other pericyte markers was largely determined by cytologic appearance. Conclusion/implicationsPericytic marker expression in PEComa may represent a true pericytic cell of origin, or alternatively aberrant pericyte marker adoption.

Anaplastic lymphoma kinase positive large B‐cell lymphoma: Literature review and report of an endoscopic fine needle aspiration case with tigroid backgrounds mimicking seminoma

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare distinct type of non-Hodgkin's lymphoma that arises in association with alterations of the ALK gene. This distinct disease entity is typically associated with an aggressive clinical course and appears in light microscopic preparations as a monomorphic population of large, immunoblast-like cells. In this report, we describe a case of ALK+ LBCL diagnosed by transgastric endoscopic ultrasound-guided fine needle aspiration (EUS FNA) of splenic hilar lymph nodes. Modified Giemsa stained direct smears from the FNA sample demonstrated large lesional cells with foamy cytoplasm and macronucleoli admixed with small lymphocytes in tigroid backgrounds, mimicking the cytologic appearance of seminoma. Ancillary immunohistochemical studies subsequently confirmed the diagnosis of ALK+ LBCL with the lesional cells being immunoreactive for CD138, VS38c, MUM1, ALK1, and lambda light chain. The cohesiveness of the cells, the cellular morphology, and the tigroid backgrounds were all pitfalls for accurate diagnosis of this rare specific type of lymphoid malignancy by cytology. To our knowledge this is the first case report detailing the diagnosis of ALK+ LBCL by EUS FNA and the first report describing a glycogen-rich tigroid background in direct FNA smears. Establishing a refined diagnosis in cases of this rare form of LBCL is necessary, as therapies targeting ALK may be of value in clinical management. Diagn. Cytopathol. 2017;45:148-155. © 2016 Wiley Periodicals, Inc.

Immunohistochemical analysis of the novel marginal zone B-cell marker IRTA1 in malignant lymphoma

Marginal zone lymphoma (MZL) is a low-grade B-cell lymphoma derived from marginal zone B cells. Because of a lack of specific immunohistochemical markers, MZL is mainly diagnosed based on the cytological appearance and growth pattern of the tumor. Marginal zone B cells were recently shown to selectively express immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), but the antibody used in that study is not commercially available. We therefore investigated the IRTA1 expression in nonneoplastic lymphoid tissues and 261 malignant lymphomas, examining the ability of a commercially available antibody to accurately diagnose MZL. Among 37 MZLs, 23 of 25 extranodal MZLs of mucosa-associated lymphoid tissue (MALT lymphomas), 3 of 6 splenic MZLs and 3 of 6 nodal MZLs were positive for IRTA1. Among the 98 diffuse large B-cell lymphomas, 33 were positive for IRTA1, including 1 of 38 follicular lymphomas, and all precursor B-lymphoblastic (2/2) and T-lymphoblastic (7/7) leukemia/lymphomas. Other mature B-cell and T-cell lymphomas, and Hodgkin lymphoma were negative for IRTA1. In MALT lymphoma, positive cells were detected mainly in intraepithelial and subepithelial marginal zone B cells. In 1 case of grade 3 follicular lymphoma, IRTA1 was also expressed in the area of large cell transformation. When tumors were classified as germinal center B cell-like (GCB) or non-GCB using the algorithm of Hans, positive expression of IRTA1 was correlated significantly with non-GCB diffuse large B-cell lymphomas (P < .05). These results demonstrated the ability of the commercially available IRTA1 antibody to distinguish MALT lymphoma from other low-grade B-cell lymphomas.

Abstract 4272: Organoids and patient-derived tumor xenograft of pancreatic adenocarcinoma share morphological and genetic features with the primary tumor

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death, with a 5-year overall survival rate &amp;lt;7%. Several active systemic therapies are now available for PDAC. Personalizing therapy may be improved with the development of realistic tumor models from a patient's explanted tumoral tissue. Human pancreatic tumor patient-derived xenografts (PDX) implanted into immunodeficient mice and tumor organoids grown in vitro 3D culture are two promising models. However, it is uncertain if these models are histopathologically and genetically similar to the primary PDAC. Histopathological comparison of sections from PDX tumor, organoids, and primary PDAC from a 63-year-old female patient were performed on paraffin embedded tissue. H&amp;E and immunohistochemical staining for cytokeratins (CK7, CK20), p53, Claudin-4, and CEA were performed. DNA and mRNA sequencing was performed. Both PDX and organoids exhibited histopathological features remarkably consistent with the original patient tumor including the histologic grade (moderately differentiated), cytological appearance (irregular nuclear membranes, open chromatin and prominent nucleoli), mitotic activity (5 -7/10 HPF), and immunohistochemical profile. The PDX and organoids demonstrated diffuse moderate-to-strong positivity for CK7, CEA, p53, and Claudin-4 and focal weak positivity for CK20 - all similar to the primary tumor. The immunohistochemical staining pattern was consistent with mRNA sequencing of the primary tumor which showed that CEA, Claudin-4 and p53 expression were ∼960-fold, ∼27-fold and ∼3 fold higher respectively (vs. benign pancreatic tissue). DNA sequencing revealed somatic mutations in KRAS and TP53 genes seen in &amp;gt;90% and ∼70% of PDACs respectively, and a few rare somatic mutations, such as a sodium leak channel (NALCN) mutation, seen in ∼3% of PDAC. Both PDX and organoid models of PDAC maintain key histological features, immunohistochemical profile and basic gene expression pattern akin to the primary tumor. These findings suggest that PDXs and organoids have the potential to serve as reliable pathophysiological models for optimizing individual therapy for patients with PDAC. Citation Format: Isabel Romero Calvo, Ashwin Akki, Andrey Ugolkov, Mary M. Buschmann, Samantha M. Sparrow, Teresa Barry, Margaret Eber, Tongjun Gu, Shuang Qin Zhang, Hedy Kindler, William Dale, Kevin Roggin, Andrew P. Mazar, Kevin P. White, Christopher R. Weber. Organoids and patient-derived tumor xenograft of pancreatic adenocarcinoma share morphological and genetic features with the primary tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4272.