Small Bowel Neuroendocrine Neoplasms-A Review.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rapidly evolving small bowel tumors, and the patients are asymptomatic at the initial stages. Metastases are commonly observed at the time of presentation and diagnosis. This review addresses the small bowel NEN (SB-NEN) and its molecular, histological, and imaging features, which aid diagnosis and therapy guidance. Somatic cell number alterations and epigenetic mutations are studied to be responsible for sporadic and familial SB-NEN. The review also describes the grading of SB-NEN in addition to rare histological findings such as mixed neuroendocrine-non-NENs. Anatomic and nuclear imaging with conventional computed tomography, magnetic resonance imaging, computed tomographic enterography, and positron emission tomography are adopted in clinical practice for diagnosing, staging, and follow-up of NEN. Along with the characteristic imaging features of SB-NEN, the therapeutic aspects of imaging, such as peptide receptor radionuclide therapy, are discussed in this review.

Interactive Pathology Tutorial in Neoplastic Hematology Disorders for Medical Hematology-Oncology Fellows.

Hematology-oncology (HO) fellows receive limited instruction in the process of establishing a diagnosis for hematologic neoplasms, and learning neoplastic hematology often occurs in limited encounters. In the current study, we developed a web-based interactive pathology tutorial in neoplastic hematologic disorders for HO fellows to work up simulated cases and establish the diagnosis. An online system ("Pathology Playground") was utilized to load case materials including microscopic images and ancillary studies. Twelve high-yield simulated cases of common leukemias and lymphoma were included. At the beginning of each case, trainees review the clinical history and slide images, and then, they are given the option to request additional pathology work-up. Based on the results, they can enter their diagnostic impression. If the diagnosis is correct, the user is shown a short educational presentation. If the diagnosis is not correct, the user gets notified by the message "Incorrect." The tutorial was integrated in the educational curriculum of our HO fellowship program, and bimonthly teaching sessions were held to review two cases each time. During the sessions, trainees request ancillary studies to complete the diagnostic work-up using the software and interpret the findings. As the case is being worked up by the trainee, the hematopathologists and HO fellowship program director discuss the findings, the appropriate work-up tools, and the implications on management. All of our six HO fellows attended the sessions, and a survey from the trainees showed high ease of use of the system and they viewed it as a very useful educational tool. A pre-test and post-test were administered for one of the sessions, and the result showed improvement in the average from 62 to 73%. Expanding the use of this online interactive tutorial and incorporating additional cases would enhance its value as a learning resource.

The prognostic significance of duodenal wall invasion in pancreatic adenocarcinoma.

OBJECTIVE: The most recent edition of the American Joint Committee on Cancer Staging Manual (AJCC, 8th edition) relies only on tumor size for staging resectable pancreatic adenocarcinoma, and the presence of duodenal wall invasion (DWI) no longer has an impact on staging. However, very few studies have evaluated its significance. In this study, we aim to evaluate the prognostic significance of DWI in pancreatic adenocarcinoma. METHODS: We reviewed 97 consecutive internal cases of resected pancreatic head ductal adenocarcinoma, and clinicopathologic parameters were recorded. All cases were staged according to the 8th edition of AJCC, and the patients were divided into two groups based on the presence or absence of DWI. RESULTS: Out of our 97 cases, 53 patients had DWI (55%). In univariate analysis, DWI was significantly associated with lymphovascular invasion and lymph node metastasis (AJCC 8th edition pN stage). In univariate analysis of overall survival, age > 60, absence of DWI, and African American race were associated with worse overall survival. In multivariate analysis, age > 60, absence of DWI, and African American race were associated with worse progression-free survival and overall survival. CONCLUSION: Although DWI is associated with lymph node metastasis, it is not associated with inferior disease-free/overall survival.

Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

BACKGROUND: Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. METHODS: A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. RESULTS: Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). CONCLUSION: Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Dedifferentiated Melanoma With Expression of Cytokeratin and GATA3 in a Patient With History of Breast Carcinoma.

Melanoma is one of the great mimickers in pathology because it has diverse morphologies and can be mistaken for carcinoma or sarcoma. In most cases, immunochemistry is helpful in supporting the diagnosis and excluding other differentials. However, metastatic melanoma may lose immunohistochemical melanocytic markers and express nonmelanocytic lineage markers, which often poses a diagnostic dilemma and may be misdiagnosed as a poorly differentiated carcinoma or sarcoma. We report the case of a 52-year-old woman who had a history of recurrent melanoma on her right shoulder with axillary lymph node metastasis (BRAF V600K-mutated melanoma) and right-side breast-invasive ductal carcinoma (stage pT1b N0sn). One year later, she presented with a left-sided chest wall mass and enlarging left axillary lymph nodes. Needle core biopsies were obtained from both lesions, and histologic examination showed a poorly differentiated tumor with pleomorphic/anaplastic morphology and necrosis. The tumor cells were strongly immunoreactive for GATA-3 without expression of melanocytic markers (S100, Melan A, HMB45, SOX10, MITF, and tyrosinase). The history of melanoma prompted molecular analysis, and the lesion was found to harbor the BRAF V600K mutation, consistent with metastatic dedifferentiated melanoma. Recognition of metastatic dedifferentiated melanoma is important to avoid misdiagnosis of carcinoma, especially in patients with a previous history of carcinoma.

Lymphoma in autopsy cases.

Lymphoproliferative disorders cause significant morbidity and mortality, either related to the disease itself or therapy complications. Some cases of lymphoma may have vague clinical presentation, especially in the absence of lymphadenopathy, and a clinical work up may not be conclusive. Our study focuses on autopsy cases of lymphoma patients, emphasizing clinically unsuspected cases. Autopsy records from the last 20 years at our institution were searched, and the clinical parameters were recorded. Fifteen cases of lymphoma were identified, and 5 cases were diagnosed at the time of autopsy. Most B-cell lymphoma cases were mainly nodal disease, while T-cell lymphoma cases had widespread extra-nodal disease. Most deaths in B-cell lymphoma are due to infection/therapy induced immunosuppression, whereas T-cell lymphoma deaths are due to organ infiltration by lymphoma. Postmortem examination may reveal clinically unsuspected lymphoma, especially in rapidly deteriorating patients with vague presentation such as skin rash, bowel obstruction/bleeding or pacemaker malfunction.

Epithelioid Myofibroblastoma of the Breast: A Report of Two Cases with Discussion of Diagnostic Pitfalls.

Mesenchymal lesions of the breast are uncommon lesions which present diagnostic dilemmas for even the most experienced pathologists. Here, we present two cases of the epithelioid-variant of myofibroblastoma which were misdiagnosed as malignant lesions. Careful integration of clinical presentation, imaging, and close examination of the gross, histologic, and immunohistochemical findings can assist in differentiating these challenging lesions and avoiding diagnostic pitfalls.

Recurrent invasive ductal carcinoma of the breast with metastasis to the uterine cervix: A case report.

This article presents a case of cervical metastasis from recurrence of invasive ductal carcinoma of the breast >20 years after initial diagnosis. The diagnosis was made after the patient presented with three months of intermittent post-menopausal vaginal spotting. She underwent palliative radiotherapy combined with chemotherapy and was disease free at the time of writing. Cervical metastasis of a primary breast cancer is extremely rare and can present with a variety of symptoms. This case report highlights the importance of life-long gynecologic care and surveillance in patients with a history of breast cancer.

Hepatic preservation injury: severity of hepatitis C recurrence and survival after liver transplantation.

BACKGROUND: Preservation injury in the HCV liver transplant population has been reported to correlate with poorer survival outcomes compared to preservation injury in the non-HCV liver transplant population. However, determinants of progression to cirrhosis in HCV infection remain poorly defined in this population. AIM: This study aimed to determine if the presence and severity of preservation injury impact the acceleration of HCV recurrence and survival after liver transplant. METHODS: We retrospectively reviewed liver transplant HCV patients over a 10-year period. Biopsies from postoperative day 7 were assessed for preservation injury and 4- and 12-month biopsies were assessed for fibrosis. Patients with Ishak fibrosis >0.8 Units/year were considered rapid fibrosers. RESULTS: Our study group consisted of 255 patients. The mean age was 49.3 years old, 180 (70.6 %) were male, and 221 (86.7 %) were Caucasian. The incidence of preservation injury on the 7-day biopsy was 69.0 %. A strong correlation between postoperative peak AST within the first week and preservation injury was found. The overall prevalence of rapid fibrosers at 4 months, 1 and 2 years was 47.4, 75.2, and 58.9 %, respectively. The prevalence of rapid fibrosers at 4 months, 1 and 2 years between patients with or without preservation injury was not statistically significant (p = 0.39, p = 0.46, and p = 0.53, respectively). No differences were seen between patients with and without PI in terms of patient and graft survival. CONCLUSION: In this study, the presence and severity of preservation injury were not associated with development of rapid HCV recurrence or worsening in survival.

HPV Associated Squamous Cell Carcinoma in the Rectal Tonsil.

Mucosa-associated lymphoid tissue has been reported throughout the gastrointestinal tract including rectum. Rarely, a nodular proliferation of predominantly submucosal lymphoid tissue in the rectum has been documented as rectal tonsil. Here we report a patient with HPV-associated squamous cell carcinoma of the rectal tonsil, presenting as a polyp. Previously, rare reports of HPV-associated lymphoepithelial carcinoma have been reported in the literature. We are presenting an extremely rare occurrence and emphasizing the importance of appropriate nomenclature based on the pathogenesis of the neoplasm.

Pathology Playground: An Interactive Web-Based System for Pathology Unknowns With Immunohistochemistry and Molecular Studies.

CONTEXT.­: Anatomic pathology slide unknown conferences are usually limited to a microscopic slide, slide images, or a virtual slide that is previewed prior to a conference. The answer is provided at a conference along with the ancillary studies, such as immunohistochemical or molecular studies, that enabled the diagnosis. In this rigid system the learner never gains experience with an appropriate workup for cases that will enable the definitive diagnosis. OBJECTIVE.­: To develop an interactive system in which the user can work through a difficult case, ordering stains and other special studies, ideally leading to more involvement and retention. DESIGN.­: An online system was developed using HTML, PHP Hypertext Preprocessor, and JavaScript for ordering and result display. When the user selects a study, an image or text result is displayed. Studies include immunohistochemistry, cytogenetics, flow cytometry, molecular, and radiology. The user then selects the diagnosis and, if correct, is shown some additional didactics. RESULTS.­: Unknown conferences were held at 3 institutions using this novel teaching method that allowed residents to work up unknown cases. Conferences are available online (http://www.drdoubleb.com/unknowns/) and include general, soft tissue, and hematopathology cases. Evaluations were obtained that showed that residents enjoyed the system, considered it better than standard unknown sessions and lectures, and wanted more sessions. CONCLUSIONS.­: This system was very highly received by the residents in all programs, who enjoyed getting immediate results and being able to work through interesting cases. More widespread use of this system could make for an effective learning tool.

Diffuse Large B-cell Lymphoma of the Orbit With Intracranial Extension: A Rare Entity.

Primary diffuse large B-cell lymphoma of the orbit is a rare diagnosis that accounts for less than 1% of all non-Hodgkin's lymphoma (NHL) cases. We present here the case of a middle-aged woman with a past medical history of intellectual delay and hypothyroidism who presented with a large diffusely infiltrating mass of the left orbit. A biopsy of the lesion during the patient's hospitalization confirmed a diagnosis of diffuse, large B-cell lymphoma. Due to extensive local invasion, she was deemed a poor surgical candidate. While inpatient, she was started on systemic chemotherapy and discharged with close follow-up planned with the oncologic and surgical teams.

Randomized, controlled trial of standard, large-capacity versus jumbo biopsy forceps for polypectomy of small, sessile, colorectal polyps.

BACKGROUND: Polypectomy with cold biopsy forceps is a frequently used technique for removal of small, sessile, colorectal polyps. Jumbo forceps may lead to more effective polypectomy because of the larger size of the forceps cup. OBJECTIVE: To evaluate the efficiency of cold jumbo biopsy forceps compared with standard forceps for polypectomy of small, sessile, colorectal polyps. DESIGN: Randomized, controlled trial. SETTING: Outpatient endoscopy center. PATIENTS: This study involved 140 patients found to have at least one eligible polyp defined as a sessile polyp measuring ≤6 mm. INTERVENTION: Polypectomy with cold biopsy forceps. MAIN OUTCOME MEASUREMENTS: Complete visual polyp eradication with one forceps bite. RESULTS: In 140 patients, a total of 305 eligible polyps were detected (151 removed with jumbo forceps and 154 with standard forceps). Complete visual eradication of the polyp with one forceps bite was achieved in 78.8% of the jumbo forceps group and 50.7% of the standard forceps group (P < .0001). Biopsies from the polypectomy sites of adenomatous polyps thought to be visually completely eradicated with one bite showed a trend toward a higher complete histologic eradication rate with the jumbo forceps (82.4%) compared with the standard forceps (77.4%), but the difference did not reach statistical significance (P = .62). The withdrawal time for visual inspection of the colon and time to perform polypectomies were significantly shorter in the jumbo forceps group (mean 21.43 vs 18.23 minutes; P = .02). LIMITATIONS: Lack of blinding to the type of forceps used. CONCLUSION: The jumbo biopsy forceps is superior to the standard forceps in removing small, sessile polyps. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00855790.).

Gamma-Delta Large Granular Lymphocytic Leukemia: A Diagnostic Dilemma.

We report an initial diagnostic dilemma case of a 60-year-old male who presented with worsening hemolytic anemia, thrombocytopenia, and acute kidney injury requiring hemodialysis. His presentation was initially suspected to be secondary to thrombotic thrombocytopenic purpura (TTP) and he was treated with intravenous immunoglobulin (IVIG) and plasmapheresis. Despite treatment, he failed to improve during his admission leading to further workup revealing gamma-delta T-cell large granular lymphocytic (γδ T-LGL) leukemia. In this paper, we will discuss the features, workup, and treatment of this rare malignancy.

Flow Cytometric Findings in Primary Effusion Lymphoma: A Report of Two Cases.

Primary effusion lymphoma (PEL) is a rare B-cell lymphoma that usually occurs in the setting of HIV infection, and it is associated with Human Herpesvirus-8 (HHV-8). Diagnosis of PEL is usually established in cell centrifuge, cell block, or tissue examination, and there are few reports describing flow cytometry findings in PEL. We report two male patients (a 34-year-old and a 56-year-old) with a history of HIV infection. The first patient presented with ascites and abdominal pain, and the second patient presented with chest pain and parapneumonic pleural effusion. Cavitary fluid examination showed large pleomorphic neoplastic lymphoid cells with plasmablastic morphology. Flow cytometry analysis of the neoplastic lymphocytes showed increased forward scatter and side scatter with intermediate to a high level of CD38 expression. In one patient, lymphoma cells showed bright CD45 expression with dim expression of CD19 and kappa light chain. There was no significant expression of CD20 or any T/NK cell markers in either case. Immunohistochemistry for CD30 was positive in one patient. Immunohistochemistry for HHV-8 and in situ hybridization for Epstein-Barr virus-encoded small RNAs (EBER) was positive on cell blocks in both cases, consistent with the diagnosis of primary effusion lymphoma. PEL should be considered in the differential diagnosis of CD20-negative hematopoietic neoplasms, and flow cytometry may provide helpful clues for the diagnosis of PEL as part of the workup for pleural effusion with cytologically malignant cells.

Primary Effusion Lymphoma Presenting As Parapneumonic Pleural Effusion.

Primary effusion lymphoma (PEL) is a rare form of high-grade non-Hodgkin's lymphoma that usually occurs in patients with compromised immunity or human immunodeficiency virus (HIV) infection. PEL is a B-cell lymphoma that principally presents as effusions without a tumor mass. We present a case of a 56-year-old African-American male with a medical history of HIV admitted to the hospital with right lung lower lobe pneumonia and parapneumonic effusion. Thoracentesis and pleural fluid cytology led to the diagnosis of PEL. He received treatment with chemotherapy and antiretroviral therapy (ART). The emphasis is to investigate immunocompromised patients presenting with pleural effusion for PEL, as it is a rare ailment with a high mortality rate.

Concomitant Gastric Malignancy and Hepatocellular Carcinoma.

Multiple primary malignant tumors (MPMTs) are two or more separate malignancies found at different sites concurrently. Prior studies have shown that the most common tumor associations in MPMTs are typically between two tumors in the digestive system. We present a case of a male patient in his 60s who initially presented with melena and was found to have a clean-based gastric ulcer on initial endoscopic evaluation. Repeat endoscopy on later admission revealed persistent ulceration. Biopsy showed Epstein-Barr virus (EBV) positive lymphoepithelioma-like gastric carcinoma (LELGC), a rare gastric malignancy. The patient underwent endoscopic ultrasound (EUS) for assessment of tumor depth and involvement of perigastric lymph nodes, but was incidentally found to have a liver lesion. Biopsy of the liver lesion was positive for hepatocellular carcinoma (HCC) with no morphologic similarity to the gastric malignancy. This case highlights a rare finding of MPMTs. In addition to the diagnosis of a rare gastric malignancy, the patient developed a well-known but uncommon phenomenon of non-cirrhotic HCC associated with hepatitis C virus (HCV). Due to an increasing number of advances in cancer therapy that are leading to increased survival times, clinicians can expect for a patient to develop MPMTs in their lifetime. A high index of suspicion must exist for the possibility of MPMTs because treatment options and outcomes can be vastly affected by their findings.

Rectal neuroendocrine neoplasms: what the radiologists should know.

Neuroendocrine neoplasms of the rectum (R-NENs) are rare; however, their incidence has increased almost threefold in the last few decades. Imaging of R-NENs includes two primary categories: anatomic/morphologic imaging comprised of endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and functional/molecular imaging comprising of planar scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). The management depends on stage, dimension, atypical features, histological grade, and lymphovascular invasion (LVI). Low-risk local R-NENs can be resected endoscopically, and high-risk or locally advanced neoplasms can be treated with radical surgery and lymphadenectomy and/or chemoradiation. The review article focuses on imaging illustrations and discusses applications of different imaging modalities in diagnosing and managing R-NENs.

Post-Transplant Lymphoproliferative Disorder: A Rare Case of CNS Involvement following Renal Transplant.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare immunosuppression complications affecting 5% of transplant patients. Isolated central nervous system (CNS)-PTLD without nodal or extra-nodal organ involvement is rarely reported and is difficult to diagnose due to the non-specific clinical manifestations and imaging features overlapping with other common CNS lesions. CASE PRESENTATION: We present a case of a 72-year-old female subjected to a renal transplant 11 years ago with progressively worsening headaches and confusion. Imaging revealed vasogenic edema in the left frontal and bilateral temporal lobes. She was subjected to a craniotomy and excisional biopsy to obtain tissue for diagnostic and therapeutic interventions. Pathology examination showed atypical EBV-positive lymphoplasmacytic infiltrate, consistent with Polymorphic type PTLD. CONCLUSIONS: Patients diagnosed with PTLD need to have close monitoring of immunosuppressive medications while in the hospital. Early diagnosis is essential for patient survival with PTLD, as their health can deteriorate fast.