bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipemic Interference in Basic Metabolic Panels: Increasing the Lipemia Index Threshold in Order to Decrease the Frequency of Ultracentrifugation
Authors: Krenzer Joseph , Nelson Alyson , Robakowski Trisha , Grant Kevin , Galior Kornelia , Hackenmueller Sarah A
Published: October 2020

Introduction

Lipemia in clinical chemistry samples is a problematic form of interference. Clearing these samples for routine testing can be time consuming and increases the turn-around time for these specimens. In our laboratory, samples with a lipemia index >50 (L-index) are manually inspected and visibly lipemic specimens are cleared by ultracentrifugation.

Objective

The objective of this study was to determine at what L-index ultracentrifugation of lipemic BMP specimens is necessary prior to sample testing to ensure accurate results.

Methods

Specimens consisted of routinely ordered basic metabolic panels (BMP) that met current criteria for ultracentrifugation, which included an L-index >50 as measured on the Abbott Architect c8000 and visual lipemia. Specimens meeting these criteria were ultracentrifuged and retested. The difference of the pre-ultracentrifuged and post-ultracentrifuged result was evaluated and put into a percent to find the ‘percent difference’ and evaluated against the total allowable error (TEa) for each analyte. If the difference observed following ultracentrifugation was less than or equal to 50% of the TEa, clearance of lipemia by ultracentrifugation was considered unnecessary. Values from all BMP component tests were analyzed in order to find an L-index threshold at which samples need to be ultracentrifuged which could be applied to the entire panel. The report of lipemic indices for BMPs for the month of January 2020 were extracted from the laboratory information system to evaluate the potential impact of altering the L-index threshold for ultracentrifugation.

Results

Based on the acceptance criteria of ≤50% of TEa, L-index thresholds for Na, K, Cl, calcium, glucose, creatinine, CO2 and BUN were <203, <410, <287, <387, <410, <285, < 153 and <285, respectively. All the calculated differences or percent differences for each analyte did not exceed 50% of the TEa for a given analyte when the L-index was 150 or less. Adjusting the L-index to 150 and applying it to the 195 lipemic BMP samples in January 2020, would have potentially decreased the number of samples requiring ultracentrifugation to 24 lipemic BMPs (88% reduction).

Conclusion

These data suggest that an L-index greater than 150 can be used for all analytes within a BMP as the threshold for requiring ultracentrifugation. The BMP is one of the most frequently ordered tests in our laboratory and consistently accounts for a substantial portion of the lipemic samples that require ultracentrifugation. Increasing the L-index at which samples will be ultracentrifuged from 50 to 150 would potentially result in an 88% reduction in one month of BMP samples requiring ultracentrifugation.
Development and Validation of Leukocyte Enzyme Activity Assay by LC-MS/MS for Diagnosis of Krabbe Disease and Other Lysosomal Storage Diseases
Authors: Liao Hsuan-Chieh , Mitchell Laura , Sadilkova Katerina , Dickerson Jane , Jack Rhona , Anna Scott
Published: October 2020

Background

Deficiency of the lysosomal enzyme galactosylcerebrosidase (GALC) causes Krabbe disease. The diagnosis for Krabbe disease includes measurement of GALC enzymatic activity by radioisotope assay or accumulation of metabolite psychosine. To improve current diagnostic workflow and assay performance, we developed and validated a leukocyte enzymatic assay by using liquid chromatography tandem mass spectrometry (LC-MS/MS) for lysosomal storage diseases.

Methods

Leukocytes were separated and extracted from whole blood samples, and total protein was quantitated by BCA method. Commercialized and multiplexed substrates, internal standards, and buffer were incubated with cell lysates. The lysosomal enzymes in leukocytes metabolized the artificial substrate into product which is structurally identical to the internal standard. Liquid-liquid extraction was performed and supernatant was dried down and reconstituted. Liquid chromatography separation was achieved by Waters CSH C18, 2.1 x 50 mm column and Acquity UPLC system. A Waters Xevo TQS tandem mass spectrometer was used for mass detection.

Results

Enzymatic reaction products for six lysosomal enzymes were chromatographically resolved from substrate breakdown products through 3.5 minutes gradient liquid chromatography. Intra-assay imprecision was determined by 11 replicates of samples containing low and high concentration (CV<15%). Carryover was determined by assaying triplicates of cell lysate-free cocktails directly after injection of high enzyme activity sample (less than 0.1%). No matrix effect was found. The GALC enzyme activity was calculated and standardized by corresponding product and internal standard ratios from 5-point standard curve. The range of enzyme activity from three, known affected patients is 0.01–0.07 (nmol/hr/mg protein); whereas, two identified carriers had enzyme activate in the range of 0.14–0.40 (nmol/hr/mg protein). The reference interval was established from 63 residual, unaffected samples and was 0.12–5.97 (1.44±1.44) nmol/hr/mg protein.

Conclusions

A simple and multiplexed LC-MS/MS assay was developed which can measure small amounts of residual GALC enzyme activity in leukocytes. This confirmatory assay will aid in the diagnosis and prognosis (i.e. differentiate disease severity) of Krabbe disease and other lysosomal storage disorders.
Synovial Metaplasia of the Endometrium
Authors: Yurtsever N , Truskinovsky A
Published: October 2020

Introduction/Objective

Synovial-like metaplasia is well known to accompany breast implants, but it can also rarely be found in the endometrium, associated with intrauterine devices. We present two cases of endometrial synovial-like metaplasia.

Methods

The hysterectomy specimens were diagnosed at Northwell Health and reviewed at the departmental Consensus Conference. Immunostains for cytokeratin AE1/AE3 were performed on the endometrium. The histopathologic findings were correlated with the clinical information.

Results

Both patients had had intrauterine devices placed for birth control. One, a 47-year-old female with a family history of Lynch syndrome and newly diagnosed with a corresponding mutation, underwent prophylactic hysterectomy. The second patient, a 50-year-old female with a history of uterine prolapse, was experiencing stress urinary incontinence, for which she underwent supracervical hysterectomy. Both patients had intrauterine devices in place at the time of hysterectomy.

Both uteri showed endometrial synovial-like metaplasia. It was associated with a complete absence of the endometrial surface epithelium. The synovial-like cells were eosinophilic, plump and elongated, were palisaded perpendicular to the endometrial surface and were negative for cytokeratin AE1/AE3, which immunostain also confirmed the absence of the endometrial surface epithelium and the presence of some residual deeper endometrial glands.

Conclusion

Endometrial synovial-like metaplasia is a rare entity described in patients with intrauterine devices. The mesodermal-derived endometrium is apparently able, when exposed to a semi-mobile foreign body, to develop a way to minimize friction by mimicking synovium, similar to the connective tissue facing breast implants. Such surface must be better at withstanding chronic friction than the regular endometrial epithelial surface, leading to this unusual and fascinating change. Since the resulting surface mimics synovium perfectly, both morphologically and immunohistochemically, and serves a very similar mechanical purpose, we propose to call this phenomenon, wherever it is found, “synovial metaplasia” instead of the current term “synovial-like metaplasia.”
Primary Intestinal-type Adenocarcinoma of the Vulva Causing Secondary Extramammary Paget Disease
Authors: Forsythe D J , Weisman P
Published: October 2020

Casestudy

A 65-year-old woman with a known history of anogenital extramammary Paget disease presented with a pedunculated lesion arising from the vulvar vestibule near the urethral meatus, discovered during a routine surveillance exam.

Results

Biopsy of the lesion revealed an adenocarcinoma with villoglandular architecture and pseudostratified columnar epithelium with goblet cells that is arising in direct continuity with the uninvolved squamous mucosa. In addition to the villoglandular component, an area of dyscohesive cells with signet ring morphology within a mucinous background was present. Biopsy of a lesion inferior to the index mass showed Paget disease with similar morphology to the invasive adenocarcinoma. By immunohistochemistry (IHC), the invasive adenocarcinoma was diffusely positive for CK20, CK7, and CDX-2 with patchy staining for p16. Metastasis was excluded by colonoscopy, mammography, and PET-CT. Additional IHC stains for GCDFP-15, GATA-3, PAX-8, S100, p63, and PSA were all negative on subsequent biopsies performed for mapping the extent of disease. These features supported a diagnosis of primary intestinal-type adenocarcinoma of the vulva and pointed to this tumor as a source of her Paget disease.

Conclusion

Primary intestinal-type adenocarcinomas of the vulva are extremely rare with only a small number of case reports in the literature. It is suggested that these tumors acquire a colorectal phenotype due to the cloacal origin of the vulvar vestibule. No standard treatment approach has been developed due to the rarity of this disease, but the majority of reported cases have had an indolent course. To the best of our knowledge, other than this case, there is only a single additional case report in the literature of secondary Paget disease arising from this tumor type. We underscore the propensity of this tumor to cause secondary Paget disease, mimicking spread from a colorectal primary site.
Pulmonary Epithelioid Haemangioendothelioma Involving Pleura: A Case Report
Authors: Kadam maruthi V
Published: October 2020

Introduction/Objective

Pulmonary epithelioid haemangioendothelioma is a rare, low to intermediate grade tumor of endothelial origin. It is more common in middle aged women. In lung, more than 60 % of the cases present as bilateral multiple perivascular nodules on imaging raising the differential of metastasis or inflammatory cause. WWTR1- CAMTA1 fusion gene is characteristic for this entity. Evidence of pleural involvement carries a poor prognosis.

Methods

Here, we present a case of epithelioid haemangioendothelioma involving pleura in a 52-year-old woman with a long standing history of rheumatoid arthritis. Patient presented with recurrent pleural effusions and shortness of breath.

Results

A diagnosis of epithelioid haemangioendothelioma was made on her pleural decortication specimen that showed atypical vascular proliferation and confirmed by immunohistochemical staining. Subsequent right lung wedge resection performed later confirmed the presence of epithelioid haemangioendothelioma in lung parenchyma.

Conclusion

Pathologists should be aware of this rare condition that can clinically present in a very deceptive manner of recurrent effusion.
Submandibular Swelling: Initial Presentation of Metastatic Neuroblastoma
Authors: Ullah A , Mattox S N , Sliker T , Willhite D , Patel N , Doroodchi A , Hatley R , Velasquez Zarate L
Published: October 2020

Casestudy: Neuroblastoma is the most common solid tumor in the pediatric population. It is derived from neural crest cells and can arise from anywhere along the sympathetic chain. Fifty-to-sixty percent of patients with neuroblastoma present with disseminated disease. However, neuroblastoma rarely presents with metastasis to the submandibular gland or head and neck region. We present a case of a 3-year-old male with a one-month history of left submandibular swelling, lower back pain, fever, decreased urine output and constipation. An abdominal ultrasound demonstrated hydronephrosis. The ultrasound of the left mandible showed an echogenic mass with prominent Doppler flow. An excisional biopsy was performed on the left submandibular mass revealing small round blue cells with syncytial pattern, scant pink cytoplasm, and dark blue nuclei. Tumor cells were strongly positive for synaptophysin immunohistochemical stain. His urine vanillylmandelic acid and homovanillic acid were 121.7 and 79.3, respectively. Subsequent imaging revealed multifocal metastatic lesions involving the cervical, thoracic and lumbar vertebrae as well as the sacrum and bilateral iliac bones and posterior epidural soft tissue on MRI. While, CT scan demonstrated a right adrenal calcified mass that was presumed to be the primary malignancy site for his metastatic neuroblastoma. He was treated with chemotherapy and follow up was recommended. Although an initial presentation of neuroblastoma as a sub-mandibular mass is rare, diagnostic workup by way of radiography, bone marrow biopsy, and laboratory investigations is crucial in the accurate diagnosis, staging, and treatment of metastatic neuroblastoma.
A Rare Case Of CNS High-Grade Neuroepithelial Tumor With BCOR Alteration (HGNET-BCOR)
Authors: Al-Habib A , Bhattacharjee M
Published: October 2020

Introduction/Objective

HGNET-BCOR is a distinct molecular CNS tumor entity that was first identified by DNA methylation analysis in 2016. It is defined by an in-frame internal tandem duplication in exon 15 of the BCOR gene.

The BCOR mutation is not unique to this tumor entity and can be seen in other CNS tumors, as well as solid organ and hematologic malignancies. In this report, we describe the pathology in a 2-year-old girl with a posterior fossa brain tumor initially diagnosed as high-grade neuropeithelial tumor at an outside facility.

Methods

She underwent resection and adjuvant chemotherapy at the same institution. She presented later to our hospital complaining of fatigue and vomiting, and tumor recurrence on MRI. Microscopic examination of the recurrent tumor showed a relatively circumscribed lesion with atrophic cerebellar folia associated with some of the tumor fragments. Tumor cells were arranged in papillary, pseudopapillary, and rosetted patterns in a myxoid (Alcian-blue positive) background. The tumor showed regional necrosis and frequent mitoses (mitotic index ~14–15 /10 HPFs). An extensive panel of immunostains was performed.

Results

The tumor was diffusely and strongly positive only for vimentin and EGFR, with diffuse moderate staining for BCL-2, and patchy weak staining for S100 protein. There were rare, focal tumor cells with GFAP and neurofilament staining. The Ki67 labeling index was 80–90%. All other tested markers were negative. The primary tumor resection was later found to be positive for BCOR by IHC. Sequencing for exon 15 of the BCOR gene showed an in-frame internal tandem duplication.

Conclusion

These features are consistent with the diagnosis of HGNET-BCOR. The pathologic and clinical features for this rare tumor entity are not widely known. Further studies with additional patients are needed to expand our understanding of these rare tumors to develop new treatment approaches.
Massive Perivillous Fibrin Deposition and Chronic Histiocytic Intervillositis of a Placenta: Rare co-existence
Authors: Ozluk E , Cotelingam J , Ong M
Published: October 2020

Introduction/Objective

Massive perivillous fibrin deposition (MPFD) and chronic histiocytic intervillositis (CHI) of the placenta are both very rare entities individually. They both are associated with reccurent loss of the fetus.

Methods

Here we report a placenta with coexisting MPFD and CHI. Patient is a 24-year-old African American female who has a history of spontaneous abortion at the 10th week when she was 18. Her latest pregnancy is complicated by intrauterine growth retardation and she eventually losses the fetus at 20th week of gestation.

Results

Histopathology reveals extensive fibrin deposition of the perivillous area and the histiocytic infiltration of the intervillous spaces which is highlighted by CD68 staining.

Conclusion

This is the second literature report of a co-occurrence of MPFD and CHI to our knowledge. Pathologists must be familiar with these entities and inform the obstetricians because these placental lesions often result with recurrent loss of fetus.
An Early Hands-On Introduction To Grossing And Frozen Section Technique For First-Year Residents
Authors: Owczarczyk A B , Toth N , Skala S L
Published: October 2020

Introduction/Objective

First-year pathology residents begin their training with variable experience in anatomic pathology. At the University of Michigan, we have recently instated an introductory rotation (“Introduction to Surgical Pathology” [ISP]) all new residents experience prior to their core surgical pathology rotations.

Methods

For the first two weeks of ISP, residents learn to gross under the supervision of certified Pathologists’ Assistants. Residents gross biopsies to gain familiarity with dictation and grossing software prior to learning how to approach larger resections. Specific feedback about the content and organization of gross descriptions is provided by the rotation director, and residents are encouraged to review slides from complex specimens they grossed. After orientation, including a lab tour and simulated frozen sections, residents spend two weeks on-service learning to triage specimens (including breast resections and lymphoma work-ups), prepare and cut frozen sections, and participate in frozen reporting. We analyzed the effect of the experience on 8 residents with a 14-question (multiple choice and short answer) pre- and post-rotation quiz and through review of anonymous feedback.

Results

Overall, 7/8 residents improved on the post quiz, while one resident’s performance slightly decreased. Average scores improved by 5.1 (of 36) points or 14.2%. Scores markedly improved on questions related to cold ischemia time, lymphoma protocol, and frozen section documentation (1–4 residents correct pre- to all correct post- rotation). Residents had difficulty answering questions related to appropriate frozen section requests and mandatory specimen photography, but reported feeling somewhat confident about their ability to gross and to prepare frozen sections. Feedback revealed an appreciation of rotation organization, clear expectations, frozen section simulation, and rotation director availability for feedback and questions.

Conclusion

Overall, ISP is a subjectively and objectively valuable rotation. The quiz results and resident feedback have highlighted areas for future improvement, including more effective education about the role of frozen section in surgical management.
Objective Histologic Characterization of Trophoblastic Proliferations
Authors: Perez C , Worrell H , Lieberman R , Skala S L
Published: October 2020

Introduction/Objective

Placental site nodules (PSNs) are rare intermediate trophoblastic lesions characterized by hyalinized cellular aggregates that are small, well-circumscribed, non-necrotic, and paucicellular. PSNs are generally incidental in gynecologic specimens. ETTs are malignant proliferations of intermediate trophoblasts and are generally larger, with nuclear atypia, and higher mitotic rate. Atypical placental site nodules (APSNs) are histologically intermediate between PSN and ETT and not well characterized in the literature to date. There exists room for more objective characterization of PSN and APSN. We use objective measurements to characterize trophoblastic proliferations based on size, location, mitotic rate, number of trophoblasts per high-power field (t-HPF), ki-67 index, beta-hCG, time since last pregnancy, presence of calcification or necrosis, and clinical follow-up.

Methods

The surgical pathology database of a single large academic institution was searched for cases of “placental site nodule,” “atypical placental site nodule,” “epithelioid trophoblastic tumor,” and “placental site trophoblastic tumor”. Clinical and morphologic data were recorded for each case. Ki-67/cytokeratin AE1/AE3 dual immunohistochemical stains were performed to assess the proliferative index of the trophoblastic cells.

Results

70 cases of trophoblastic lesions (53 PSN, 4 APSN, 5 ETT, 8 PSTT) were identified. Results include: PSNs were on average 3.2 mm, 56.5 t-HPF, and 2.6% ki-67. APSNs 4.3 mm, 97.8 t-HPF, and 6.4% ki-67. ETTs 16.5 mm, 161.8 t-HPF, and 12.2% ki-67.

Conclusion

Objective measurements of trophoblastic lesions, as well as correlation with clinical data, may be useful for more accurate classification of these lesions, especially by those who encounter them rarely. To date, the clinical risk, optimal management, and risk for progression of APSNs are not well characterized and thus are worthy of additional study and description. For example, in our data, 14 cases originally signed out at PSN were at least 4 mm, which may re-classify them as APSN.
Aberrant Diffuse Intense CD10 Expression In P16 Positive Undifferentiated Endometrial Carcinoma: A Diagnostic Dilemma
Authors: Derakhshandeh R , Kallakury B
Published: October 2020

Introduction/Objective

High-grade endometrial neoplasms frequently pose a diagnostic challenge on purely histologic evaluation due to their ambiguous morphologic features. High grade endometrioid adenocarcinoma, serous carcinoma, undifferentiated carcinoma, and a minority of sarcoma cases can present with a solid growth pattern.

Methods

We present a 59-year-old patient who underwent a hysterectomy and bilateral salpingo-oophorectomy for a biopsy proven FIGO grade 2 endometrial carcinoma.

Results

Grossly, the entire endometrial cavity was involved by a hemorrhagic tumor. Microscopic examination showed the entire specimen to be replaced by predominantly non-cohesive diffuse sheets of mitotically active, pleomorphic cells without any glandular, papillary, serous or clear cell features.The differential diagnosis included undifferentiated carcinoma, serous carcinoma, carcinosarcoma, stromal sarcoma and other tumors including high- grade lymphoma. By immunohistochemistry, the tumor cells showed variable positivity for CK7, EMA, CK19, CK18, CK8, AE1/AE3, pan-keratin, CAM5.2, CD56, synaptophysin, p53, cyclinD1 and with a high Ki-67 proliferation index of 80%. The tumor was diffusely/intensely positive for CD10 and P16 while being negative for ER, PR, PAX8, HPV, mesenchymal and lymphoid markers.

While diffuse/intense CD10 positivity and ER/PR negativity raised a concern for stromal sarcoma component, the above phenotype confirmed an aggressive/high grade carcinoma. Diffuse/intense p53 and p16 expression raised a consideration of serous carcinoma, but morphology and absence of PAX-8 failed to support this diagnosis.

Undifferentiated carcinoma of the endometrium is a high-grade carcinoma which has been recognized as a distinct entity with diffuse p16 and p53 positivity in the absence of PAX-8 and hormone receptors. Positive vimentin, along with a negative HPV, confirmed the endometrial rather than cervical origin of this neoplasm.

Conclusion

By reporting this case, we draw attention to the previously unreported diffuse intense CD10 expression in undifferentiated carcinoma of endometrium to avoid misdiagnosis with considerations that include stromal sarcoma.
Myeloid Sarcoma Involving the Central Nervous System Without Evidence of Preexisting Hematologic Disease: A Case Report
Authors: Marshall C , Sandhu A D , Mohanty A
Published: October 2020

Introduction/Objective

Myeloid sarcoma within the central nervous system is a rare presentation of an infiltrative mass of immature myeloid cells. It is typically found in association with myeloid dysplastic syndrome, myeloproliferative disorder, or acute myeloid leukemia. Rarely, it can occur in the absence of these diseases.

Methods

We present the case of 68-year-old female with worsening nausea and headaches. Brain MRI showed diffuse pachymeningeal enhancement with numerous nodular enhancing extra-axial masses overlying both cerebral hemispheres.

Results

Open biopsy of these masses showed gelatinous, hemorrhagic, brown tissue measuring 3.0 x 2.0 x 0.7 cm. Histologically, the specimen shows a diffuse polymorphous atypical myeloid proliferation consisting of all three cell lineages. There are nodules composed predominantly of large blastoid cells with 1 to 2 prominent oblong nucleoli, consistent with erythroblasts and early erythroid precursors. In between the nodules there are myeloid cells in different stages of maturation, including numerous eosinophilic precursors. Scattered megakaryocytes are also identified.

Immunohistochemistry shows positivity for E-cadherin, CD235a and spectrin which highlight the immature erythroid cells. MPO, muramidase, and CD33 are positive in myeloid elements. Eosinophilic peroxidase highlights numerous eosinophilic precursors. CD34 is positive in the endothelial cells and very rare hematopoietic cells. CD20 and PAX 5 highlights B-cells, CD3 highlights T-cells, and CD4 highlights monocytic precursors, monocytes, histiocytes and a subset of T-cells.

Conclusion

Additional work up at the time of biopsy including FLOW cytometry and bone marrow biopsies showed no evidence of hematologic pathology. In summary the histologic and immunohistochemical findings demonstrate a tumor composed of proliferating immature myeloid cells most consistent with myeloid sarcoma without any evidence of hematological disease.
Key Differences in Final Pathology Compared to Pre-Operative Clinical Diagnoses in the Liver Transplant Population: Implications for Quality Improvement
Authors: Attaway C C , Furth E E , Tondon R , Fortuna D , Talwar A
Published: October 2020

Introduction/Objective

The pre-transplant clinical evaluation of patients with liver disease are critical components determining prognoses, eligibility and placement on the transplant waiting (eg. hepatocellular carcinoma (HCC) may decrease time on list), and surgical planning for the type of biliary anastomosis performed. For example, patients with Primary Sclerosing Cholangitis (PSC) are given direct liver to small bowel anastomosis, a type prone to ascending cholangitis, compared to duct to duct types in all other etiologies, and a clinical diagnoses of alcohol-induced cirrhosis impacts the patient’s and family’s psycho-social well-being. The goal of our study was to determine the frequency and types of differences in the clinical versus liver explant pathology diagnoses.

Methods

A search for “liver explant” for all in-house cases between 7/15/2019 to 7/15/2018 and 1/1/2010 to 12/31/2010 identified 105 and 108 cases, respectively. For each case, pre-operative clinical diagnoses determined by the electronic medical record was compared to pathologic diagnosis. Cases with non-concordance were divided into two groups: 1. Concordant etiology but incidental malignancy identified in explant 2. Non-concordant etiology.

Results

In the 2018–2019 group, of the 105 liver explants, 6 had concordant etiology but previously unknown HCC and 9 cases had non-concordant diagnoses. Similarly, the 2010 group, of the 108 liver explants, 6 had consistent etiology but previously unknown HCC and 8 cases non-concordant diagnoses. Of the total 17 non-concordant cases, 4 carried a pre-transplant diagnosis of PSC and were reversed to autoimmune hepatitis (2), chronic rejection, and primary biliary cholangitis on explant pathology and 3 carried a diagnosis of alcohol-induced cirrhosis and were reversed to portal tract venopathy, viral hepatitis, and alpha-1 antitrypsin.

Conclusion

There are clinically significant discordances between pre-transplant and explant diagnoses with 6% incidental malignancies and 8% etiology changes. Of particular importance for anastomoses complications and psycho-social issues are patients with a pre-operative diagnoses of PSC or alcohol whose diagnosis was changed by pathology explant assessment, respectfully. Strategies to refine and improve pre-operative liver disease diagnoses particularly with regard to biliary and alcohol diagnoses will be explored.
Mixed Acinar-Neuroendocrine Carcinoma of the Stomach: A Case Report and Review of the Literature
Authors: Coppola D , Hough B , Saller J
Published: October 2020

Introduction/Objective

Mixed Acinar Neuroendocrine Carcinoma (MACNEC) is rare and usually occurrs in the head of the pancreas. This is an epithelial neoplasm of the pancreas exhibiting both acinar and neuroendocrine differentiation. Each component must represent at least 30% of the tumor. Extrapancreatic acinar cell carcinoma arising in the stomach are also rare and represent <1% of all gastric neoplasms. Here we report a case of MACNEC arising in the stomach of a 60 yo female and we review the literature.

Methods

The specimen was formalin-fixed and paraffin embedded. 4-microns sections of the tumor block were stained for hematoxylin and eosin and immunostained for CAM5.2, Chromogranin, synaptophysin, trypsin, chymotrypsin, BCL10, HepPar1 and AFP using a Ventana Discovery XT automated system (Ventana Medical Systems, Tucson, Ariz) as per manufacturer’s protocol with proprietary reagents.

Results

The patient presented with heartburn and weight loss. An upper endoscopy revealed an ulcer along the stomach greater curvature. Endoscopic ultrasound revelaed an hypoechoic round mass involving the submucosa. Imaging showed no lesions in the pancreas. A stomach wedge resection was performed: a 1.2 x 0.6 x 0.5 cm. submucosal tan-brown mass was found. Microscopically the tumor had alternated solid/acinar areas with cords/ribbons neuroendocrine-like areas. Both components were immunohistochemically positive for keratin (CAM 5.2), chromogranin (diffuse), and synaptophysin (patchy). The trypsin, chymotrypsin and BCL10 immunostains were patchy and stained 30 to 40% of the tumor. The immunostains for HepPar-1 and AFP were negative. These results support the diagnosis of MACNEC. Pancreatic heterotopia was not identified in the tissue examined. The margins of resection were free of tumor. The tumor was staged as T1NXMX. The patient has been under close surveillance for 3 years and she has no radiographic evidence of tumor recurrence or metastases.

Conclusion

We found only 6 prior cases of MACNEC originating in the stomach. They had similar histopathologic and immunohistochemical features. In the absence of a pancreatic lesions, in this patient the tumor may have originated from ectopic pancreatic tissue or from a pluripotent stem cell in the stomach.
Partial Nephrectomy For a Presumed Single Renal Mass Revealing Multiple Tumor Histologies: A Series of 4 Patients
Authors: Arora S , Rogers C G , Arora K , Abou Shaar R , Kezlarian B , Modi M , Gupta N , Williamson S R
Published: October 2020

Introduction/Objective

Renal mass biopsy is known to have a low but unavoidable diagnostic error rate. However, the occurrence of multiple adjacent masses mimicking one mass clinically has been minimally studied.

Methods

We report a series of four patients who were radiologically presumed to have a single renal mass and treated with partial nephrectomy, yet who were found to have multiple demarcated renal cell carcinoma histologies at pathologic evaluation.

Results

All were men aged 63–70 years. Grossly, tumors were red brown with scant, bright yellow foci in one of them. Dominant tumors followed by smaller tumors were: patient 1 - clear cell renal cell carcinoma (5.0 cm), clear cell papillary renal cell carcinoma (0.5 cm), and papillary adenoma (0.6 cm); patient 2 - clear cell renal cell carcinoma (1.5 cm) and clear cell papillary renal cell carcinoma (0.5 cm); patient 3 - papillary renal cell carcinoma (5.0 cm) and eosinophilic variant of chromophobe renal cell carcinoma (1.0 cm); patient 4 - chromophobe renal cell carcinoma (4.0 cm) and clear cell papillary renal cell carcinoma (0.6 cm). Immunohistochemical studies for cytokeratin 7, carbonic anhydrase IX, high molecular weight cytokeratin, CD10, and alpha-methyl acyl-CoA racemase (AMACR) confirmed the separate components in all.

Conclusion

This series adds to the spectrum of causes that may contribute to discordant results of renal mass biopsy and resection specimens. Secondary smaller tumors appear to be predominantly nonaggressive histologies, enriched for clear cell papillary renal cell carcinoma. Pathologists and urologists should be aware of this occurrence when considering the role of renal mass biopsy and interpreting the results.
Poorly Differentiated Chordoma with Rhabdoid Features
Authors: Kashi M , Agarwal A , Villanueva J
Published: October 2020

Casestudy: Chordoma is an uncommon primary malignant tumor of the bone showing notochordal differentiation. The current World Health Organization classifies chordoma into three subtypes: conventional, chondroid, and dedifferentiated.

Poorly differentiated chordoma (PDC) is a newly described variant of chordoma, with its own distinct features in terms of age distribution (common in pediatric and young adults), histopathology (lack of physaliphorous cells and chondromyxoid matrix), immunohistochemical and molecular characteristics (loss of SMARCB1/INI1 expression) and clinical outcome (poor prognosis with rapid onset of local recurrence and metastasis).

Herein, we report the case of a 43 year old man with history of fall and injury of tailbone 2 years prior, who presented with pain and swelling at the sacrcoccygeal region and intermittent numbness in the legs. MRI of the pelvis showed a 9.8 cm lobulated mass centered on the sacrum with osseous destruction of S5 through coccyx, with intralesional hemorrhage, and mild heterogeneous enhancement. Biopsy of the sacrococcygeal mass demonstrated a malignant neoplasm composed of lobules of epithelioid cells with abundant eosinophilic cytoplasm showing focal vacuolization, and mild to moderate nuclear pleomorphism with an average 3 mitoses per high power field (400x). Immunohistochemically, the neoplastic cells were positive for pancytokeratin, CAM 5.2, vimentin and brachyury. They had loss of SMARCB1 (INI1) and were negative for S100, CK7, CK20, desmin and actin. The location, imaging studies, morphologic features and immunohistochemical profile were consistent with poorly differentiated chordoma with rhabdoid features. With its specific clinical, morphologic, immunophenotypical, and molecular features, PDC may be recognized as a chordoma subtype in a future WHO classification. According to current knowledge, the diagnosis of PDC should be restricted to cases with brachyury expression (specific for notochord tumors) and INI1 protein loss, especially in tumors of pediatric and young patients, regardless of cellular characteristics.
Isolated Right Ventricular Non-compaction as a Cause of Death in Cornelia de Lange Syndrome
Authors: Youssef B I , Zayko M , Gertsen E
Published: October 2020

Introduction/Objective

We report the case of a 32-year-old white male with a past medical history of bipolar disorder, autistic spectrum disorder, and Cornelia de Lange Syndrome (CdLS), who was admitted to the ED with cardiac arrest. Resuscitative efforts were unsuccessful. The autopsy revealed an isolated right ventricular non-compaction.

Methods

The non-compaction of the ventricular myocardium is a type of cardiomyopathy caused by aberrant embryogenesis, often presenting with other congenital cardiac defects, especially in syndromic patients. Such is the case with Cornelia de Lange Syndrome, in which multiple cardiac anomalies are commonly seen. However, only a few cases of ventricular non-compaction were reported for patients with CdLS. To our knowledge, this is the first case of CdLS with death attributed to the isolated right ventricular non-compaction cardiomyopathy.

Results

CdLS is characterized by intellectual disability, distinctive facial features, growth retardation, hirsutism, and malformation of multiple organ systems. In general, ventricular non-compaction is defined by the persistence of deep intertrabecular recesses that communicate with both the ventricular cavity and the coronary circulation. The two main diagnostic criteria include the absence of well-formed papillary muscles and more than 50% penetration of invaginated endocardial recesses toward the epicardial surface. Additional features include the presence of staghorn shaped endocardial recesses, endomyocardial thickening, and endocardial fibrosis. Clinical diagnosis is based on ECG, echocardiography, and ventricular angiography. Magnetic resonance imaging is also helpful in providing a good correlation with echocardiogram for localization and the extent of non-compaction.

Conclusion

In the general population, the non-compaction involves the left ventricle predominantly. The prevalence of iRVNC remains underestimated, and although echocardiography can aid in the diagnosis, the morphological assessment of RV continues to be difficult and challenging. Pathologists should be aware of non-compaction as a cause of sudden cardiac death in syndromic and non-syndromic patients when performing autopsies.
Metastatic Prostate Adenocarcinoma in Rectal Polyp: A Rare Clinical Presentation
Authors: Singh A , Behl P , Craig R
Published: October 2020

Introduction/Objective

Prostate cancer is known to metastasize to bone, lymph node, lungs, liver, and brain, with the GI tract being an uncommon site of metastasis. More commonly, prostate adenocarcinoma involves GI tract by direct colonic extension. Interestingly, few cases have been reported with metastasis presenting as a GI polyp.

Methods

We herein report a case of 69-year-old African American male who was diagnosed with metastasis of prostate adenocarcinoma presenting as rectal polyp. The patient originally presented with lower urinary tract symptoms. Further examination revealed PSA level of 220. The patient underwent TRUS-guided prostate biopsy which showed prostate adenocarcinoma with Gleason score of 9 (grade group 5). Follow-up CT and radioisotope scans showed direct extension of prostate lesion into bladder, seminal vesicle and rectum. Metastases were noted to right lesser trochanter, L5 vertebra and retroperitoneal lymph nodes. Colonoscopy was performed 1 month after prostate biopsy due to abnormal CT finding of rectal wall thickening. Endoscopy found a single 0.5 mm sessile polyp which was resected by cold snare polypectomy.

Results

Microscopically, a nodule of tubular glands arranged back to back containing pleomorphic cells with large nuclei, prominent nucleoli, and vacuolated cytoplasm was seen underlying normal colonic mucosa. The malignant cells expressed prostate specific antigen (PSA) and phosphate specific acid phosphatase (PSAP). It was negative for CK7 and CDX2, rendering a diagnosis of metastatic prostate adenocarcinoma. Patient is currently receiving androgen deprivation treatment and enzalutamide with future plans for external beam radiation. The germline alteration testing was positive for BRCA2 which is associated with increased risk of prostate cancer.

Conclusion

Albeit rare, it’s important for pathologists to be aware of this entity presenting uncommonly as a rectal polyp, particularly given the history of prostate adenocarcinoma which could be mistaken for colonic adenocarcinoma. In rare cases, tumor seeding following TRUS-guided prostate biopsy has also been implicated.
PD-L1 Expression is Associated with Poorer Survival in Anal Squamous Cell Carcinoma: Analysis from an Urban Public Hospital
Authors: Monsrud A , Avadhani V , Mosunjac M , Krishnamurti U
Published: October 2020

Introduction/Objective

Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal squamous cell carcinoma. This study aims to correlate PD-L1 expression with clinicopathologic factors and clinical outcomes.

Methods

After IRB approval, formalin-fixed, paraffin embedded sections of 58 cases of anal invasive squamous cell carcinoma from 2010–2018 were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). Of these, 51 cases could be evaluated for PD-L1 expression. Greater than 1% of tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +). PD-L1 expression was correlated with age, sex, stage, HIV status, HIV viral load, CD4 count, disease progression, and cancer specific survival. Kaplan-Meier curves for overall survival (OS) were plotted and compared using the log rank test. Cox regression analysis was performed to identify significant prognostic factors (Two-tailed p< 0.05 was considered statistically significant).

Results

Of the 51 cases evaluated, PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases. The median cancer specific survival (MCSS) was lower in PD-L1 positive cases (22 months) compared with PD-L1 negative cases (48 months), p=0.008. The number of cancer specific deaths was higher in the PD-L1 + group (50% vs. 30%), but not statistically significant (p= 0.23). Other factors that were not significantly different between the two groups were age, sex, stage, HIV status, HIV viral load, and number of patients with cancer progression. Patients with positive PD-L1 had worse OS (5yr OS: 41% for PD-L1 positive vs 64% for PD-L1 negative; p=0.02). On multivariate analysis, PD-L1 positive status remained statistically significant for worse OS, HR = 6.5 (95% CI 1.2–33.9), p=0.027.

Conclusion

The median cancer specific survival and 5-yr OS is significantly lower in the PD-L1 positive group. PD-L1 positive status is associated with a worse prognosis independent of stage, HIV status, HIV viral load, and CD4 count. The study highlights the potential of PD-L1 targeted therapy in better management of anal squamous cell carcinoma.
Metronomic Chemotherapy After Palliative Radiotherapy In Rare Soft Tissue Sarcomas; An Insight Into Radiation Therapy And The Immune Response
Authors: Madabhavi I , Sarkar M , Sandeep S , Madabhavi N , Modi M , Naik U
Published: October 2020

Introduction/Objective

Soft tissue sarcomas (STSs) account for less than 1% of the overall human burden of malignant tumors. The intent of treatment in metastatic STSs is palliative and prognosis is dismal. This study aims to evaluate the role of low dose radiotherapy and low dose oral metronomic therapy in heavily pretreated metastatic infrequent STSs.

Methods

This research was conducted in a prospective observational manner in a tertiary care center. A total of 16 cases met the inclusion criteria for enrollment in the study group. The diagnosis of all subtypes of STS was confirmed by histopathology and immunohistochemistry or cytogenetic studies. All the enrolled patients with metastatic STSs who were treated with surgery and two lines of chemotherapy were initially treated with low dose radiotherapy of twenty Gy in five fractions or thirty Gy in ten fractions according to ECOG performance status of the patient.

Results

Out of 16 patients, seven patients (43.75%) were treated with 20Gy, 5# and 9 patients (56.25%) were treated with 30Gy, 10 # radiotherapy (RT). Out of 16 patients, four were of malignant fibrohistiocytic sarcoma, three were angiosarcoma, three were malignant phylloides tumor of the breast, and two were fibrosarcoma. One patient from each of the following subtypes inflammatory myofiroblastic tumor, leiomyosarcoma, synovial sarcoma, and dermato fibrosarcoma protuberance. Out of 16 patients, seven (43.75%) had a partial response (PR), nine (56.25%) had stable disease (SD) at 3 months and all the patients had stable disease (SD) at 6 months of evaluation. All the patients had enjoyed a better quality of life as compared to their life during injectable chemotherapy.

Conclusion

Targeted low dose radiation and metronomic chemotherapy lead to quantifiable antiangiogenic effects, immune effects in the local tumor microenvironment, and influences circulating immune mediators and anti- angiogenesis that could potentially help eradicate disease both within and outside the radiation treatment field.
Metastatic Malignant Peripheral Nerve Sheath Tumor to the Brain Demonstrating Clonal Evolution by Cytogenetic Analysis
Authors: Suddock J T , Broehm C J , SantaCruz K S
Published: October 2020

Casestudy: Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive, uncommon soft tissue sarcomas that arise from peripheral nerves or pre-existing benign nerve sheath tumors. Local recurrence and metastases are known to occur, though metastasis to the brain is very rare. Limited treatment options impart the need to better characterize these tumors. We present a case of a 26-year-old female with a history of a 5.5 cm MPNST of the left chest, who presented with brain metastasis two years later. The tumors were found to have similar histologic and cytogenetic findings with clonal evolution evident in the metastasis. The original tumor exhibited a proliferation of spindled cells arranged in sweeping fascicles accompanied by numerous mitotic figures and areas of geographic necrosis. The malignant cells were patchy positive for S100 and CD34 and negative for SOX10 and GFAP. Cytogenetic analysis revealed three related abnormal clones, all of which demonstrated add(2)(p25) and add(22)(q12). Monosomy 6 was identified in one clone, and near triploidy and triploidy was identified in the other two clones. Additionally, numerous whole chromosome gains and losses were present. The patient underwent surgical resection and was treated with adjuvant radiation. Two years later, a PET scan revealed a hypermetabolic left temporal lobe mass. MRI revealed a 4.9 x 4.5 cm destructive lesion invading through the temporal bone and involving brain parenchyma. The mass was resected and submitted for pathologic evaluation revealing similar histologic findings to the original, though S100 and SOX-10 were negative. Cytogenetic analysis revealed two related abnormal clones which shared add(2)(p25) and add(22)(q12) as well as an additional copy of add(22)(q12). One clone showed near triploidy with loss of several whole chromosomes. These findings are remarkable for recurrent metastatic disease to the brain and uniquely show clonal evolution of the metastatic tumor.
Coexistence of Microsatellite Stable (MSS) and Instable Colorectal Cancer (CRC) Primary Colon Cancers: A Case Report and Brief Review of Literature
Authors: Wassimi S
Published: October 2020

Introduction/Objective

Microsatellite stable (MSS) and Instable colorectal cancer (CRC) as primary colon cancers differ in their pathological features and biological behavior including response to treatment. In general, MSI-high CRC has a better prognosis and a more favorable response to treatment. To our knowledge, the co-occurrence of the microsatellite stable and unstable CRCs in the same person has not been reported in the literature. Herein, we present the case report of 78 year African American female who presented to us with this condition.

Methods

A literature search of publication up to March 2020 in PubMed was conducted on the occurrence of microsatellite stable and unstable CRCs in the same individual. The literature search was limited to English language only. The following words were used in the search engine of PubMed: “Microsatellite stable colorectal cancer + unstable colorectal cancer and colorectal cancer + same patient”. No articles were identified.

Results

A search using the terms “coexistence of MSS and MSI CRC in the same individual” identified 45 articles. No case report or article discussing the presence of coexisting MSS and MSI CRC in the same individual was identified

Conclusion

Identification of MSI CRC is important, as MSI may serve as a screening tool for detecting Lynch Syndrome, a prognostic marker for patient outcome, and as a predictive marker for response to chemotherapy and to immunotherapy. Whether coexistence of MSI and MSS favorably affects the prognosis of the disease is unknown.