scholarly journals Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification

2019 ◽  
Vol 143 (11) ◽  
pp. 1304-1316 ◽  
Author(s):  
Steven C. Weindorf ◽  
Noah A. Brown ◽  
Jonathan B. McHugh ◽  
Aaron M. Udager
Keyword(s):  
Molecular Basis ◽  
Clinical Utility ◽  
Molecular Classification ◽  
Accurate Diagnosis ◽  
Molecular Testing ◽  
Diagnostic Challenge ◽  
Pertinent Literature ◽  
Molecular Features ◽  
Relative Rarity

Context.— Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. Objective.— To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. Data Sources.— Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. Conclusions.— Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools—including immunohistochemistry and in situ hybridization—may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.

scholarly journals Detecting an ALK Rearrangement via Liquid Biopsy Enabled a Targeted Therapy-based Approach for Treating a Patient with Advanced Non-small Cell Lung Cancer

2018 ◽  
Vol 14 (1) ◽  
pp. 38 ◽  
Author(s):  
Alejandro R Calvo ◽  
Gabriel H Ibarra ◽  
Cecile Rose T Vibat ◽  
Veena M Singh
Keyword(s):  
Liquid Biopsy ◽  
Clinical Utility ◽  
Tumor Tissue ◽  
Molecular Testing ◽  
Tissue Analysis ◽  
Alk Rearrangement ◽  
Blood Draw ◽  
Diagnostic Biopsy

Initial diagnostic biopsy procedures often yield insufficient tissue for molecular testing, and invasive surgical biopsies can be associated with significant cost as well as risk to the patient. Liquid biopsy offers an alternative and economical means for molecular characterization of tumors via a simple peripheral blood draw. This case report describes the ability of liquid biopsy to detect an ALK translocation where tissue analysis by fluorescence in situ hybridization was negative for the genetic alteration. Identification of an ALK rearrangement in circulating tumor cells from a blood specimen led to sequential targeted therapies that included crizotinib followed by alectinib. The patient demonstrated outstanding clinical response during treatment with each of the prescribed ALK inhibitors. This case demonstrates the clinical utility of Biocept’s liquid biopsy to detect actionable biomarkers by surveying the systemic landscape of a patient’s disease where identification of the same genetic drivers may be missed in analyses of heterogeneous tumor tissue.

scholarly journals Superficially Spreading Endocervical Adenocarcinoma in situ with Multifocal Microscopic Involvement of the Endometrial Surface: A Case Report with Emphasis on the Potential for Misdiagnosis Based on Endometrial Curettage Specimens

2020 ◽  
Vol 13 (3) ◽  
pp. 1530-1536
Author(s):  
Inwoo Hwang ◽  
Jiyeon Lee ◽  
Kyue-Hee Choi ◽  
Jiheun Han ◽  
Hyun-Soo Kim
Keyword(s):  
Final Diagnosis ◽  
Accurate Diagnosis ◽  
Surface Epithelium ◽  
Apoptotic Bodies ◽  
Small Tumor ◽  
Histological Features ◽  
Endocervical Adenocarcinoma ◽  
Tumor Tissues ◽  
Mitotic Figures

Misdiagnosis of endocervical adenocarcinoma (EAC) as endometrial endometrioid carcinoma (EEC) is one of the major concerns when evaluating endometrial curettage specimens. It is difficult to differentiate EAC involving the endometrium from EEC, particularly when the specimens have only a few small tumor fragments. We report a case of endocervical adenocarcinoma <i>in situ</i> (AIS) with multifocal microscopic involvement of the endometrium. The endometrial curettage specimen obtained from an 82-year-old woman consisted of a large volume of blood and fibrin, with small endometrial tissue fragments showing microscopic foci of atypical glandular proliferation. Based on the presence of complex glands with stratified mucin-poor columnar epithelium and intermediate-grade nuclear atypia, a preoperative diagnosis of grade 1 EEC was made. However, the hysterectomy specimen revealed an endocervical AIS involving the endocervix and low uterine segment. Frequent mitotic figures and apoptotic bodies, characteristic of AIS, were present. The endometrium showed a few microscopic foci of atypical glandular proliferation involving the surface only. Their histological features were similar to those of the endocervical AIS. Immunohistochemically, the atypical glands exhibited block p16 positivity. The final diagnosis was a superficially spreading endocervical AIS with multifocal microscopic involvement of the endometrial surface epithelium. In summary, small tumor tissues in an endometrial curettage may lead to misdiagnosis of AIS or EAC as EEC, especially when the pathologists are unaware of the possibility of microscopic endometrial involvement of AIS or EAC. The origin of the tumor can be correctly determined based on a combination of histological features and immunostaining. Endocervical AIS involving the endometrium should be included in the differential diagnosis of neoplastic glandular lesions in endometrial curettage specimens. An accurate diagnosis in these cases is important because of its significant implications for clinical management.

Plasmablastic Myeloma Versus Plasmablastic Lymphoma; Is MYC Rearrangement Helpful Towards A Precise Diagnosis?

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S105-S105
Author(s):  
M Khedr ◽  
Y Yusuf ◽  
L Aftab
Keyword(s):  
Reference Range ◽  
Final Diagnosis ◽  
Plasmablastic Lymphoma ◽  
Bone Lesions ◽  
Molecular Testing ◽  
Diagnostic Challenge ◽  
Plasma Cell Neoplasm ◽  
Hiv Antibodies ◽  
Precise Diagnosis ◽  
Diagnostic Work

Abstract Introduction/Objective Plasmablastic myeloma (PBM) is a rare and aggressive plasma cell neoplasm. Differentiating PBM from plasmablastic lymphoma (PBL) represents a diagnostic challenge, as both diseases have overlapping cytomorphologic and immunophenotypic features. Genetic mutations in MYC occur in a majority of PBL cases but rarely in PBM, thus can theoretically be used to differentiate between both neoplasms. Methods We report a case of a 53-year-old female who presented with a rapidly growing mass in her right mandible. Biopsy revealed circumscribed nodules of immunoblastic cells with moderate cytoplasm, large vesicular nuclei and large prominent nucleoli. Apoptotic debris and brisk mitoses were present. Molecular testing revealed a C-MYC rearrangement. The location of the neoplasm and the above described morphological features were suggestive of PBL, especially with a positive C-MYC rearrangement. The neoplastic cells were positive for CD138, MUM1,CD56 and kappa; and negative for CD45, CD20, PAX5, CD3, CD5, CD30, EBER-ISH, HHV8, ALK-1, Lambda, EMA, CD21, CD23, pancytokeratin, CK20, CK7, Cam5.2, chromogranin, synaptophysin, HMB45, S100, P16, P40. MIB-1 showed high positivity, approximately 95%. Results Patient underwent further diagnostic work up, her HIV antibodies result were negative however, she was found to be anemic (Hemoglobin 6.6 g/dl; reference range 12-16 g/dl) and hypercalcemic (Calcium 12.3 mg/dl; reference range 8.5-10.5 mg/dl). PET scan revealed multiple hypermetabolic lytic bone lesions. The bone marrow biopsy showed 80% cellularity with extensive involvement by atypical plasmacytic cells forming large clusters. The patient’s final diagnosis was PBM. Conclusion Differentiating PBM from PBL is essential as treatment is different. Although MYC rearrangement in PBM is not common, it has been demonstrated and therefore should not be used to exclude this diagnosis. Here, we highlight the importance of correlating detailed clinical, radiological, laboratory, histological and genetics data for reaching the final diagnosis.

scholarly journals EPEN-45. NORMALIZING AND FACILITATING GENOMIC TESTING AT DIAGNOSIS IN PEDIATRIC EPENDYMOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Emily Owens Pickle ◽  
Ana Aguilar-Bonilla ◽  
Amy Smith
Keyword(s):  
Current Practice ◽  
Molecular Classification ◽  
Molecular Data ◽  
Molecular Profiling ◽  
Genomic Testing ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Pediatric Ependymoma ◽  
Need Support ◽  
Almost All

Abstract The current consensus is that diagnosis and treatment of ependymoma should be based upon clinical and molecular classification. As we move into this paradigm, it is important all ependymoma cases undergo tumor collection, preservation, and molecular profiling at diagnosis. Our group of 6 sites gathered data on a cohort of 72 ependymoma cases. Sites were asked to report known molecular findings; 60/68 eligible cases (88%) did not include genetic findings. The low number of cases with molecular findings was surprising and since cases were diagnosed from as early as 2004, we asked collaborators to share their current practice in profiling (e.g., how frequently; in what setting were ependymomas sent for testing) to try and better understand current practice at sites. Since the publication of ependymoma molecular data, sites with a neuro-oncology program report sending almost all newly diagnosed ependymomas for molecular testing, whereas current practices at sites without dedicated neuro-oncology were less consistent. Profiling in the setting of relapse was more frequently reported at all centers. The implementation of molecular testing at diagnosis may need support at sites without dedicated neuro-oncology. Lead investigators for upcoming ependymoma clinical trials will need to think carefully about the logistics of profiling at centers where this is not standard practice at diagnosis.

scholarly journals Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study

2019 ◽  
pp. 1-18
Author(s):  
Olga Kondrashova ◽  
Gwo-Yaw Ho ◽  
George Au-Yeung ◽  
Leakhena Leas ◽  
Tiffany Boughtwood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real Time ◽  
Targeted Therapies ◽  
Clinical Management ◽  
Clinical Utility ◽  
Advanced Ovarian Cancer ◽  
Molecular Profiling ◽  
Molecular Testing ◽  
Low Grade ◽  
Ovarian Carcinomas

PURPOSE The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. PATIENTS AND METHODS A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C. RESULTS Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy samples of two patients, consistent with clinical platinum/poly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling. CONCLUSION ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.

scholarly journals An Unsuspected Finding of t(9;22): A Rare Case of Philadelphia Chromosome-Positive B-Lymphoblastic Lymphoma

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Prajwal Boddu ◽  
C. Cameron Yin ◽  
Rashmi Kanagal-Shamanna ◽  
Guillin Tang ◽  
Beenu Thakral ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
Philadelphia Chromosome ◽  
Lymphoblastic Lymphoma ◽  
Accurate Diagnosis ◽  
Biopsy Specimens ◽  
B Lymphoblastic Lymphoma ◽  
Prophylactic Chemotherapy

While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup. While the FISH returned negative, PCR testing unexpectedly detected BCR-ABL1 fusion transcripts at a low level of 0.48%. Given their presence, we performed FISH for BCR/ABL1 rearrangement in both testicular and L5 vertebral specimens which were 80–90% positive. He subsequently received rituximab, hyper-CVAD, and dasatinib, along with prophylactic intrathecal prophylactic chemotherapy. The patient achieved a prolonged remission but eventually relapsed, 4 years later. Had it not been for this fortuitous discovery, the patient would not have been treated with tyrosine kinase inhibitors. We emphasize that FISH and PCR testing for BCR-ABL1 rearrangement are integral to arriving at an accurate diagnosis and should be routinely tested on B-LBL biopsy specimens.

scholarly journals RARE-43. FAVORABLE OUTCOME OF A YOUNG GIRL WITH RECURRENT METASTATIC PINEOBLASTOMA ASSOCIATED WITH A DICER1 MUTATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii451-iii452
Author(s):  
Adam Rossi ◽  
Gregory Verona ◽  
Ann Ritter ◽  
Hope Richard ◽  
India Sisler ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Positive Impact ◽  
Spinal Metastasis ◽  
High Grade Glioma ◽  
Young Girl ◽  
Pleuropulmonary Blastoma ◽  
High Dose ◽  
Molecular Testing ◽  
Cell Transplant ◽  
Molecular Features

Abstract Pineoblastomas have been thought to portend a poor prognosis, especially in younger children or those with metastases. Long term survivors after relapse, especially for those with metastatic disease are rare. We report a young girl with a DICER1 mutation who survived recurrent metastatic pineoblastoma. She was initially diagnosed at the age of 3 with a localized pineoblastoma, underwent gross total surgical resection, and received high dose chemotherapy with autologous stem cell transplant per COG ACNS0334 without radiation therapy. 16 months after completion of treatment, she relapsed at primary site with widespread spinal metastasis. She then received cranial spinal radiation of 3600Gy with proton beam, with boost to primary to 5580Gy, followed by chemotherapy with Temozolomide, Irinotecan and Avastin per COG ACNS0821. She is now 3 years and 3 months from completion of treatment, is doing well clinically with stable imaging findings. No particular alteration was identified from the tumor molecular testing of her initial pineoblastoma. Of note, she was diagnosed with pleuropulmonary blastoma soon after her initial diagnosis of pineoblastoma, and was found to have a DICER1 mutation (c.2062C&gt;T; pR688*) thought to be a nonsense mutation. While radiation therapy following recurrence is known to improve the outcome, more recent studies suggest that tumors lacking the molecular features of high grade glioma also has a positive impact on prognosis. In addition, we speculate that DICER1 mutations might increase sensitivity of cancer cells to some chemotherapy through modulating gene expression and /or interfering with DNA repair mechanisms, therefore, affecting treatment outcome.

Molecular bases of primary monogenic dyslipidemia

2020 ◽  
pp. 4-17
Author(s):  
О.Н. Иванова ◽  
П.А. Васильев ◽  
Е.Ю. Захарова
Keyword(s):  
Lipid Profile ◽  
Molecular Basis ◽  
Clinical Characteristics ◽  
Metabolic Disorders ◽  
Low Density Lipoproteins ◽  
Accurate Diagnosis ◽  
High Density Lipoproteins ◽  
Extreme Deviation ◽  
Low Levels ◽  
Molecular Bases

Дислипидемия - одно из наиболее распространенных метаболических нарушений, доминирующий фактор риска заболеваний сердечно-сосудистой системы. Своевременная диагностика и корректировка липидного профиля могут заметно снизить заболеваемость и смертность от сердечно-сосудистых заболеваний. Обширная гетерогенная группа заболеваний приводит к устойчивым изменениям липидного профиля. Предлагаемый обзор включает в себя описание метаболизма липидов, молекулярных основ и клинических характеристик первичных моногенных дислипидемий. Мутации двадцати пяти генов являются причиной большинства моногенных дислипидемий. На основании изменений липидного профиля выделяют пять групп фенотипов с экстремальным отклонением уровней маркеров липидного профиля: с высоким и низким уровнем липопротеинов низкой плотности, с высоким и низким уровнем липопротеинов высокой плотности, с высоким уровнем триглицеридов. Для каждого фенотипа обозначены ассоциированные гены, указан ген с чаще всего выявляемыми мутациями. Подробно описаны молекулярные основы наиболее распространенной дислипидемии, характеризующейся существенным повышением уровня липопротеинов низкой плотности - семейной гиперхолестеринемии. Генетическое тестирование пациентов с дислипидемией дает возможность постановки точного диагноза, каскадного обследования и консультирования членов семьи пациента, ранней диагностики для предотвращения или более позднего проявления осложнений. Dyslipidemia is one of the most common metabolic disorders, the dominant risk factor for diseases of the cardiovascular system. Timely diagnosis and correction of the lipid profile can significantly reduce morbidity and mortality from cardiovascular diseases. An extensive heterogeneous group of diseases leads to persistent changes in the lipid profile. This review includes a description of lipid metabolism, the molecular basis, and clinical characteristics of primary monogenic dyslipidemia. Mutations in twenty-five genes are responsible for most monogenic dyslipidemias. On the basis of changes in the lipid profile, five groups of phenotypes are distinguished with extreme deviation in the levels of lipid profile markers: with high and low levels of low density lipoproteins, with high and low levels of high density lipoproteins, with high levels of triglycerides. For each phenotype, the associated genes are indicated, the gene with the most frequently detected mutations is indicated. The molecular basis of the most common dyslipidemia, familial hypercholesterolemia, is described in detail. Genetic testing of patients with dyslipidemia makes it possible to make an accurate diagnosis, the possibility of cascade examination and counseling of the patient’s family members, the possibility of early diagnosis to prevent or later manifest complications.

Frozen Section Examination of Liver, Gallbladder, and Pancreas

2005 ◽  
Vol 129 (12) ◽  
pp. 1610-1618 ◽  
Author(s):  
Juan Lechago
Keyword(s):  
Frozen Section ◽  
Gallbladder Wall ◽  
Confounding Factors ◽  
Tertiary Referral ◽  
Pertinent Literature ◽  
Medical Centers ◽  
Frozen Tissue ◽  
Relative Rarity ◽  
Gross Examination ◽  
Frequent Presence

Abstract Context.—Frozen section of the liver is a comparatively frequent request that most often applies to a relatively limited number of situations. The only indication for frozen tissue examination of a gallbladder with any frequency is the presence of a polypoid mucosal lesion or a suspicious thickening of the gallbladder wall. A variety of intraoperative consultations may be applicable during surgery of the pancreas. Objective.—To examine the indications and pitfalls regarding the gross examination and frozen section performance for liver, gallbladder, and pancreas. Data Sources.—Author experience and review of the pertinent literature. Conclusions.—Although indications are relatively straightforward for frozen section of liver and gallbladder, handling of the pancreas specimens for frozen tissue examination is often a cause for a certain degree of anxiety. This situation is the result of a relative rarity of such specimens outside large tertiary referral medical centers coupled with a variety of confounding factors, including the presence of chronic pancreatitis with distortion of the normal structures and the frequent presence of variable degrees of dysplasia. The suboptimal preservation of the frozen tissue adds further angst to the scenario. In this article, the main issues are critically examined in light of the experience of the author and others.

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