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1.
Diagn Cytopathol ; 51(10): E273-E278, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37318678

ABSTRACT

Rectovaginal endometriosis is a severe variant of deeply infiltrating endometriosis. Laparoscopic assessment with tissue sampling remains the gold standard for diagnosis of endometriosis. However, transvaginal (TVUS) and transrectal ultrasound (TRUS) have been shown to be especially helpful in the diagnosis of deep endometriosis. We present the case of a 49-year-old female with menorrhagia, dysmenorrhea, and constipation. Upon pelvic examination, an incidental mass was palpated. A computed tomography (CT) scan revealed an anterior rectal wall mass and colonoscopy was non-diagnostic. Further work-up with MRI showed a 3.9 cm mass centered within the upper rectovaginal septum. TRUS guided fine-needle aspiration (TRUS-FNA) revealed cohesive epithelial cell groups without significant cytologic atypia and a second population of bland spindle cells. Cell block slides showed glandular epithelium with associated stroma that exhibited endometrial morphology and immunophenotype. Nodular fragments of spindle cells with smooth muscle immunophenotype and fibrosis were also present. The overall morphologic findings were consistent with rectovaginal endometriosis with nodular smooth muscle metaplasia. Medical management with nonsteroidal aromatase inhibitor with radiologic follow-up was selected. Rectovaginal endometriosis represents a type of deep endometriosis usually associated with severe pelvic symptoms. Metaplastic smooth muscle cells are a frequent component of endometriosis in the rectovaginal pouch with nodular growth and may present diagnostic challenges. TRUS-FNA is a minimally invasive procedure that can provide an accurate diagnosis of endometriosis, even in this variant of deep infiltrating disease.


Subject(s)
Endometriosis , Female , Humans , Middle Aged , Endometriosis/diagnostic imaging , Biopsy, Fine-Needle , Rectum/diagnostic imaging , Muscle, Smooth , Ultrasonography, Interventional
2.
J Am Heart Assoc ; 12(4): e027990, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36789856

ABSTRACT

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.


Subject(s)
COVID-19 , Myofibroblasts , Humans , Myofibroblasts/metabolism , SARS-CoV-2 , Collagen/metabolism , Heat-Shock Proteins/metabolism , Collagen Type I/metabolism , Phenotype , Macrophages/metabolism , Fibrosis
3.
Am J Clin Pathol ; 158(5): 655-663, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36208148

ABSTRACT

OBJECTIVES: To determine outcomes following relocation of frozen section services (FSS) and the implementation of a dedicated gastrointestinal frozen service. METHODS: We reviewed our FSS 6 months prior to and following FSS relocation. Satisfaction surveys were sent to surgeons and pathologists. Survey feedback resulted in a pilot of gastrointestinal subspecialist frozen section coverage. RESULTS: There were 1,607 and 1,472 specimens from 667 and 602 patients pre- and post-FSS relocation, respectively. There was a decline in median specimen delivery time to pathology (12 vs 10 minutes, P < .001) and an increase in median time from receipt in pathology to intraoperative diagnosis (20 vs 22 minutes, P = .008) in cases with intrapathology consultation but no change without consultation (median, 19 minutes). Intrapathology consultation decreased from 19.7% (317/1,607) to 11.5% (169/1,472) (P < .001). Discordance rates between frozen section and permanent section remained low and similar (2.0% [33/1,607] vs 2.7% [40/1,472], P = .24). There was no significant change in discordance with dedicated gastrointestinal subspecialty frozen section interpretation. CONCLUSIONS: Relocation of FSS and dedicated subspecialty interpretation may improve surgeon satisfaction but can also create workflow challenges. Pathology departments need to achieve a balance between satisfaction and adequacy to establish best frozen section coverage models.


Subject(s)
Frozen Sections , Pathology, Surgical , Humans , Frozen Sections/methods , Pathology, Surgical/methods , Referral and Consultation , Hospitals , Diagnostic Errors
4.
Ann Diagn Pathol ; 57: 151884, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35074581

ABSTRACT

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an exceedingly rare subtype of pancreatic ductal adenocarcinoma. Histologically, UC-OGC is characterized by three cell types namely, a neoplastic mononuclear cell component, non-neoplastic osteoclast-like giant cells, and a non-neoplastic mononuclear histiocytic component. The behavior of this tumor is unpredictable; but many patients survive many years after diagnosis. UC-OGC may have a better prognosis compared to conventional pancreatic adenocarcinoma due to its slower local spread, less aggressive nature, better response to surgical resection and/or chemotherapy, and fewer metastases. Due to likely differences in prognosis and significant impact on patient management, it is important to distinguish this subtype from other types of pancreatic adenocarcinoma. We report a case of a small (<1 cm) undifferentiated carcinoma with osteoclast-like giant cells of the posterior pancreatic body discovered incidentally on magnetic resonance image (MRI) scan of a middle-aged man. The radiologic and pathologic findings are presented along with a discussion of the differential diagnosis of this exceedingly rare entity.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/pathology , Giant Cells/pathology , Humans , Male , Middle Aged , Osteoclasts/pathology , Pancreatic Neoplasms/pathology
5.
Diagn Cytopathol ; 50(2): E43-E46, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34617678

ABSTRACT

Extramedullary hematopoiesis (EMH)-the proliferation of hematopoietic progenitors outside of the bone marrow (BM) is a well-known phenomenon in myeloproliferative neoplasms (MPN). Abundant literature describes EMH at various body sites in cases of MPN, and some studies showed the presence of cytogenetic changes associated with MPN in the EMH tissues. We present a case of an 80-year-old female, with a history of MPN, presenting with mediastinal adenopathy. The transbronchial fine-needle aspiration (FNA) of the mediastinal lymph node showed EMH with atypical megakaryocytes and del(13q) demonstrated by fluorescence in situ hybridization. The subsequent BM biopsy demonstrated myelofibrosis with atypical megakaryocytes harboring the same cytogenetic abnormality. Our case highlights the capability of FNA cytology for providing accurate morphologic, immunohistochemical, and cytogenetic diagnosis of clonal EMH.


Subject(s)
Bone Marrow Neoplasms/pathology , Bone Marrow/pathology , Clone Cells/pathology , Hematopoiesis, Extramedullary , Aged , Biopsy, Fine-Needle , Female , Humans , Lymph Nodes/pathology , Reticulin/metabolism
6.
Int J Qual Health Care ; 33(1)2021 Mar 11.
Article in English | MEDLINE | ID: mdl-33644816

ABSTRACT

BACKGROUND: Second opinion review of pathology cases can identify diagnostic errors that impact patient care. OBJECTIVE: We sought out to determine discrepancy rates and clinical impact of review of pathology cases to reassess our policy of review on all second opinion cases. METHODS: All second opinion pathology cases over 1 year (2018) were retrospectively reviewed for discrepancy, multiple pathologist review and clinicopathologic features via chart and slide review. Cases were categorized as no significant discordance, major discordance without management change and major discordance with management change. RESULTS: Among 4239 second opinion cases, 3.7% (156/4239) had major discordance with no change in management and 1% (42/4239) had major discordance with change in management. Discordance was significantly associated with multiple pathologist review at our institution (P < 0.001). Highest rates of discordance were observed for thyroid fine needle aspiration (15.3%, 26/170), tissue biopsy of bone/soft tissue (9.6%), endocrine (8.8%), genitourinary (6.7%), gynecologic (6.2%), hematopathology (4%), gastrointestinal/liver (3.7%) and thoracic (3%) sites. CONCLUSIONS: Our study showed a 1% major discordance rate with resulting significant change in clinical management, spread across nearly all subspecialties. Thus, we support recommendations for review of relevant outside pathology material for all patients for which review has the potential to illicit management change such as instituting a major medical or surgical therapy.


Subject(s)
Pathology , Referral and Consultation , Diagnostic Errors , Female , Humans , Retrospective Studies
7.
Ophthalmic Plast Reconstr Surg ; 37(2): 108-117, 2021.
Article in English | MEDLINE | ID: mdl-32496393

ABSTRACT

PURPOSE: There is an imperfect correlation between the histology and behavior of solitary fibrous tumor (SFT). In addition, recurrence is common, and dedifferentiation may occur over time. Preferred primary treatment is intact excision, but friable pseudocapsules and tenacious attachments can thwart this goal in the crowded, visually sensitive orbit. This study addresses the fate and appropriate management of incompletely excised orbital SFT. METHODS: Among a single surgeon's 7-case experience with orbital SFT, 3 cases involved incomplete primary excision, either before (2 cases) or after (1 case) referral. We reviewed the clinicopathologic data in these 3 cases, with follow-up intervals of 18, 21, and 52 years after initial presentation. We reviewed the English-language literature on SFT, with special attention to evolving nomenclature, orbital involvement, recurrence, malignant transformation, and management options. RESULTS: Benign versus malignant designations of SFT vary with histological and behavioral criteria. Approximately 150 orbital cases have been reported. Published rates of primary malignancy and recurrence across all histologic categories are 6% to 12% and 30% to 37%, respectively. We identified 43 well-documented recurrences (range, 6 months-33 years; median, 3 years) and 10 cases of histological dedifferentiation (range, 14 months-33 years). Because of SFT's rarity and needed follow-up intervals, the value of adjuvant therapy is not yet proven. In follow up of 18, 21, and 52 years after initial presentation, our 3 cases with incomplete excision showed either no recurrence (Case 1) or no morphological dedifferentiation (Cases 2, 3). CONCLUSION: A treatment algorithm is predicated on the completeness of surgical excision and histological features. However, we recommend case-by-case multidisciplinary decisions in a tumor-board setting.


Subject(s)
Orbital Neoplasms , Solitary Fibrous Tumors , Humans , Neoplasm Recurrence, Local , Orbit , Orbital Neoplasms/diagnosis , Orbital Neoplasms/surgery , Solitary Fibrous Tumors/surgery
8.
Ann Diagn Pathol ; 50: 151670, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33310590

ABSTRACT

BACKGROUND: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.


Subject(s)
Anal Canal/cytology , Anal Canal/pathology , Anus Neoplasms/diagnosis , Cytodiagnosis/methods , Papillomaviridae/genetics , Pathology, Surgical/methods , Academic Medical Centers , Adult , Anal Canal/virology , Anus Neoplasms/pathology , Anus Neoplasms/virology , Biopsy/methods , Cytodiagnosis/statistics & numerical data , Female , Genotype , Humans , Male , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Pathology, Surgical/statistics & numerical data , Retrospective Studies , Sensitivity and Specificity
10.
Ann Diagn Pathol ; 48: 151583, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32847795

ABSTRACT

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Squamous Cell/pathology , Pancreas/pathology , Pancreatic Neoplasms/pathology , Aged , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/surgery , Diagnosis, Differential , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Female , Humans , Mutation, Missense , Pain/diagnosis , Pain/etiology , Pancreas/diagnostic imaging , Pancreatectomy/methods , Pancreatic Neoplasms/diagnostic imaging , Proto-Oncogene Proteins p21(ras)/genetics , Splenectomy/methods
11.
Arch Pathol Lab Med ; 144(1): 47-61, 2020 01.
Article in English | MEDLINE | ID: mdl-31538798

ABSTRACT

CONTEXT.­: Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery. OBJECTIVE.­: To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics. DATA SOURCES.­: The review and analysis of the latest literature describing pancreatic cystic lesions. CONCLUSIONS.­: Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing.


Subject(s)
Pancreatic Cyst/diagnosis , Pancreatic Cyst/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Humans
12.
AACE Clin Case Rep ; 5(5): e298-e301, 2019.
Article in English | MEDLINE | ID: mdl-31967057

ABSTRACT

OBJECTIVE: Fine-needle aspiration (FNA) of a thyroid nodule is typically considered a benign procedure. Uncommonly, morphological changes can occur in the nodule or tissue after the procedure. These changes have been noted in tissues like thyroid, breast, lymph node, and prostate. The objective of this case report is to report the rare occurrence of thyroid cancer diagnosed on FNA, appearing as a necrotic mass after near total thyroidectomy and to emphasize the need for confirmation of diagnosis with histopathology. METHODS: A 69-year-old man was seen for a self-discovered neck mass. Thyroid ultrasound demonstrated a thyroid nodule with suspicious features. Ultrasound-guided FNA of the nodule was performed with a 22-gauge needle without immediate complications. RESULTS: The cytology was read as consistent with papillary thyroid cancer with a preoperative thyroglobulin level of 15,288 ng/mL (normal range is 1.6-55 ng/mL). After a near total thyroidectomy, histopathology revealed complete infarction of the tumor with no evidence of cancerous tissue remaining. Based on the pathology report, he was considered cured of the cancer and did not receive radioactive iodine therapy. CONCLUSION: The occurrence of tissue infarction following FNA of a thyroid nodule is rare, reportedly <2%. We conclude a review of the original cytology material and a thorough examination of remaining viable tissue be made. Complete evaluation for invasion of the capsule or surrounding tissue must be ascertained to decrease diagnostic errors.

13.
Head Neck Pathol ; 13(3): 512-515, 2019 Sep.
Article in English | MEDLINE | ID: mdl-29774486

ABSTRACT

Stensen's duct carcinoma (StDC) is an extremely rare neoplasm, with fewer than 40 cases reported in the literature. We report a unique case of primary StDC with papillary features and intestinal differentiation of a 74-year-old male. We discuss the radiologic and pathologic correlation along with the differential diagnosis of this rare entity.


Subject(s)
Carcinoma, Papillary/pathology , Parotid Neoplasms/pathology , Salivary Ducts/pathology , Aged , Cell Differentiation , Humans , Male
14.
Thyroid ; 28(11): 1462-1467, 2018 11.
Article in English | MEDLINE | ID: mdl-30215297

ABSTRACT

BACKGROUND: Previous studies have suggested that oncocytic variant papillary thyroid carcinoma (PTC) may be more aggressive, with higher rates of recurrent disease. The aim of this study was to evaluate characteristics and outcomes of patients with oncocytic variant PTC compared to classical PTC. METHODS: Patients with oncocytic variant PTC were retrospectively identified from 519 patients who underwent thyroidectomy for PTC between January 2009 and August 2015. Data collected included patient demographics, laboratory and pathology findings, imaging studies, treatment, and follow-up. Patients were matched 1:1 by age, sex, and TNM stage with patients who underwent total thyroidectomy for classical PTC during the same time period. RESULTS: The cohort included 21 patients, of whom 18 (86%) were female, with a median age of 53 years (range 23-68 years). All patients underwent total thyroidectomy, and 17 (81%) had a central compartment neck dissection (8 [38%] prophylactic). The median tumor size was 2.0 cm (range 0.9-6.5 cm), and four (19%) patients had extrathyroidal extension. There was no significant difference in histopathologic characteristics, including extrathyroidal extension and lymphovascular invasion, between the two groups except for an increased incidence of thyroiditis in oncocytic variant PTC (90.5% vs. 57%; p = 0.01). In oncocytic variant PTC patients who underwent central compartment neck dissection, malignant lymph nodes were found in 12 (57%) patients compared to 13 (62%) classical (p = 0.75). Lateral neck dissection was performed in 5 (24%) oncocytic variant and classical PTC patients, with metastatic lymphadenopathy found in four (a median of four malignant lymph nodes; range 1-6) and five (a median of 2.5 malignant lymph nodes; range 1-9), respectively. Radioactive iodine was administered to 18 (86%) oncocytic variant PTC and 18 (86%) classical PTC patients. At a median follow-up of 51 months (interquartile range 38-61), one oncocytic variant PTC patient had recurrent disease and underwent reoperation at 24 months. In classical PTC patients with a median follow-up time of 77 months (range 56-87 months), two (9.5%) patients had detectable thyroglobulin levels indicating early recurrence, but neither has undergone reoperation. CONCLUSIONS: Oncocytic variant PTC was present in 5% of PTC patients. Most (95%) patients remain disease-free at four years, similar to classical PTC outcomes, suggesting that oncocytic variant may not represent a more aggressive variant.


Subject(s)
Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Female , Humans , International Cooperation , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Thyroid Cancer, Papillary/surgery , Thyroid Neoplasms/surgery , Thyroidectomy , Young Adult
15.
Ann Diagn Pathol ; 36: 38-43, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30055523

ABSTRACT

Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus. The most common location is the uterine corpus, but it can also primarily arise in a variety of extrauterine locations such as pelvis, ovary, abdominal cavity, vagina, and vulva. We are reporting a case of a 47-year-old female with no significant medical history who presented with multiple pulmonary nodules. Fine needle aspiration (FNA) specimen revealed spindle cell neoplasm consistent with the diagnosis of LGESS. The differential diagnosis included neuroendocrine tumor, synovial sarcoma, solitary fibrous tumor, smooth muscle tumors, and peripheral nerve sheath tumors. The clinical, cytological, and histopathologic details of this case, as well as a discussion of the potential pitfalls and differential diagnosis of spindle cell lesions of the lung are described.


Subject(s)
Endometrial Stromal Tumors/pathology , Multiple Pulmonary Nodules/pathology , Sarcoma, Endometrial Stromal/pathology , Sarcoma, Synovial/pathology , Biopsy, Fine-Needle/methods , Diagnosis, Differential , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Endometrial Stromal Tumors/diagnosis , Female , Humans , Middle Aged , Multiple Pulmonary Nodules/diagnosis , Neoplasm Grading/methods , Sarcoma, Endometrial Stromal/diagnosis , Sarcoma, Synovial/diagnosis , Smooth Muscle Tumor/diagnosis , Smooth Muscle Tumor/pathology
16.
BMC Cancer ; 18(1): 335, 2018 03 27.
Article in English | MEDLINE | ID: mdl-29587663

ABSTRACT

BACKGROUND: Patient-derived tumor models are the new standard for pre-clinical drug testing and biomarker discovery. However, the emerging technology of primary pancreatic cancer organoids has not yet been broadly implemented in research, and complex organotypic models using organoids in co-culture with stromal and immune cellular components of the tumor have yet to be established. In this study, our objective was to develop and characterize pancreatic cancer organoids and multi-cell type organotypic co-culture models to demonstrate their applicability to the study of pancreatic cancer. METHODS: We employed organoid culture methods and flow cytometric, cytologic, immunofluorescent and immunohistochemical methods to develop and characterize patient-derived pancreatic cancer organoids and multi-cell type organotypic co-culture models of the tumor microenvironment. RESULTS: We describe the culture and characterization of human pancreatic cancer organoids from resection, ascites and rapid autopsy sources and the derivation of adherent tumor cell monocultures and tumor-associated fibroblasts from these sources. Primary human organoids displayed tumor-like cellular morphology, tissue architecture and polarity in contrast to cell line spheroids, which formed homogenous, non-lumen forming spheres. Importantly, we demonstrate the construction of complex organotypic models of tumor, stromal and immune components of the tumor microenvironment. Activation of myofibroblast-like cancer associated fibroblasts and tumor-dependent lymphocyte infiltration were observed in these models. CONCLUSIONS: These studies provide the first report of novel and disease-relevant 3D in-vitro models representing pancreatic tumor, stromal and immune components using primary organoid co-cultures representative of the tumor-microenvironment. These models promise to facilitate the study of tumor-stroma and tumor-immune interaction and may be valuable for the assessment of immunotherapeutics such as checkpoint inhibitors in the context of T-cell infiltration.


Subject(s)
Cell Culture Techniques , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Stromal Cells/pathology , Tumor Microenvironment/immunology , Cell Line, Tumor , Coculture Techniques , Humans , In Vitro Techniques , Spheroids, Cellular , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tumor Cells, Cultured
17.
Ann Diagn Pathol ; 33: 58-61, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29566949

ABSTRACT

Secretory carcinoma (SC) is a rare low-grade malignant tumor, defined by ETV6-NTRK3 fusion, identifiable by FISH. We describe a case in a 58-year-old male with a painless slowly growing 16mm palpable mass within left superficial parotid. FNA of the mass showed highly cellular specimen with moderate to large pleomorphic cells with round to ovoid nuclei with vesicular chromatin and distinct nucleoli. Cells had moderate to large amounts of vacuolated cytoplasm. Abundant globular metachromatic material, resembling that of adenoid cystic carcinoma, was noted. This material was seen extracellularly and intracytoplasmic, and stained magenta on Diff-Quik and blue-green on Papanicolaou-stained slides. The tumor cells on a cell block preparation were positive for Mammaglobin and S-100. PAS stain highlighted extracellular and intracytoplasmic secretions. FNA diagnosis was "Positive for Malignancy. Morphologic features most compatible with Mammary Analogue Secretory Carcinoma". ETV6 FISH studies as well as histologic examination of excised tumor confirmed the diagnosis. Finding the globular metachromatic material in SC, that is generally seen in adenoid cystic carcinoma, broadens a cytological differential diagnosis of both entities. Cytological differential diagnosis, clinical, histological, immunohistochemical, and molecular features of secretory carcinomas are discussed in this study.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Mucoepidermoid/pathology , Carcinoma/pathology , Mammary Analogue Secretory Carcinoma/pathology , Biomarkers, Tumor/analysis , Breast Neoplasms/diagnosis , Carcinoma/diagnosis , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Mucoepidermoid/diagnosis , Diagnosis, Differential , Humans , Male , Mammary Analogue Secretory Carcinoma/diagnosis , Middle Aged
18.
J Gastrointest Surg ; 21(11): 1793-1803, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28849366

ABSTRACT

BACKGROUND: Among patients with localized pancreatic cancer (PC), the benefit of adjuvant therapy after neoadjuvant therapy and surgery is unknown. METHODS: Patients with localized PC who completed all intended neoadjuvant therapy and surgery were categorized based on the receipt of adjuvant therapy and by pathologic lymph node status (LN-/LN+). RESULTS: Data was available from 234 consecutive patients, 121 (52%) with resectable and 113 (48%) with borderline resectable PC. Of the 234 patients, 92 (39%) were LN+ and 142 (61%) were LN-. The median overall survival (OS) for the 234 patients was 39 months, 42.3 months for patients who received any adjuvant therapy and 34.1 months for those who did not (p = 0.29). Of the 92 LN+ patients, the median OS with and without adjuvant therapy was 29.5 and 23.2 months, respectively (p = 0.02). Of the142 LN- patients, the median OS was 45 months with or without adjuvant therapy (p = 0.86). In an adjusted hazard model, additional adjuvant therapy had a significant protective effect among LN+ patients (HR 0.39; 95% CI 0.21-0.70; p = 0.002) but not in LN- patients (HR 0.89; 95% CI 0.53-1.52; p = 0.68). CONCLUSION: Among patients with localized PC who received neoadjuvant therapy and surgery, the benefit of adjuvant therapy was limited to those with node-positive disease.


Subject(s)
Antineoplastic Agents/therapeutic use , Pancreatectomy , Pancreatic Neoplasms/therapy , Aged , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Patient Selection , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
19.
Ophthalmic Plast Reconstr Surg ; 33(1): e18-e20, 2017.
Article in English | MEDLINE | ID: mdl-25719368

ABSTRACT

Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.


Subject(s)
Adenocarcinoma/pathology , Orbital Neoplasms/pathology , Aged, 80 and over , Humans , Male , Orbit/surgery , Radiotherapy, Adjuvant , Treatment Outcome
20.
Dig Dis Sci ; 61(3): 890-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26346997

ABSTRACT

BACKGROUND: Prior to withdrawing the EUS-FNA needle from the lesion, the stopcock of the suction syringe is closed to reduce contamination. Residual negative pressure (RNP) may persist in the needle despite closing the stopcock. AIMS: To determine whether neutralizing RNP before withdrawing the needle will improve the cytology yield. METHODS: Bench-top testing was done to confirm the presence of RNP followed by a prospective, randomized, cross-over study on patients with pancreas mass. Ten milliliters of suction was applied to the FNA needle. Before withdrawing the needle from the lesion, the stopcock was closed. Based on randomization, the first pass was done with the stopcock either attached to the needle (S+) or disconnected (S-) to allow air to enter and neutralize RNP and accordingly the second pass was crossed over to S+ or S-. On-site cytopathologist was blinded to S+/S-. RESULTS: Bench tests confirmed the presence of RNP which was successfully neutralized by disconnecting the syringe (S-) from the needle. Sixty patients were enrolled, 120 samples analyzed. S+ samples showed significantly greater GI tract contamination compared to S- samples (16.7 vs. 6.7%, p = 0.03). Of the 53 patients confirmed to have pancreas adenocarcinoma, FNA using S- approach was positive in 49 (93%) compared to 40 using the S+ approach (76%, p = 0.02). CONCLUSIONS: Despite closing the stopcock of the suction syringe, RNP is present in the FNA needle. Neutralizing RNP prior to withdrawing the needle from the target lesion significantly decreased GI tract contamination of the sample thereby improving the FNA cytology yield. CLINICAL TRIALS REGISTRATION NUMBER: NCT01995474.


Subject(s)
Adenocarcinoma/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Suction/methods , Syringes , Adenocarcinoma/diagnosis , Aged , Cross-Over Studies , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/secondary , Pressure
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