bluuebunny/crossref_metadata_2025 huggingface dataset:
A Shared Diagnostic Stewardship Approach to Autoimmune Encephalopathy Send-Out Testing
Authors: Sharp Cierra , Muluhngwi Penn , Fletcher Anita , Linder Mark , Snyder James , Jortani Saeed
Published: October 2020

As part of our laboratory testing utilization at University of Louisville Hospital (ULH), any send-out test ≥$500 must be assessed by the clinical chemistry fellow or pathology resident for clinical necessity and as a way to provide consultation to the ordering physician on appropriate test utilization. In 2018, we noticed a prominent increase in the volume of panels for autoimmune encephalopathy (AE) and related disorders being ordered. This was met with considerable cost to the hospital, a lack of consensus on which panels should be ordered, and poor understanding of the clinical utility of these panels. These challenges presented an ideal project for our newly-formed diagnostic stewardship committee (DSC) at ULH. Through collaboration with the DSC, we were able to form a sub-committee with the Department of Neurology to develop an algorithm-based approach for ordering of these AE panels. Our goals were to improve diagnostic utility for the betterment of patient care, improve test utilization, and decrease cost associated with panel ordering.

Prior to involvement of the DSC, we analyzed the number and cost of all AE panels ordered in 2018. We also calculated the number of positive panels and reviewed patient data to determine if a positive panel corresponded with a clinical outcome. After presenting our data to the DSC, an evidence-based approach was taken in collaboration with the Department of Neurology to develop an algorithm for AE test ordering. Results were analyzed for true positive rate, defined as a patient testing positive for an antibody with known etiology or association with AE based on result interpretation provided by Mayo Clinical Laboratories. The total cost of tests was also analyzed before implementation of the algorithm (January 1, 2019-July 31, 2019) and post-implementation (August 1, 2019-December 31, 2019).

In 2018, 77 AE panels were ordered with an estimated charge to the laboratory of $137,510. The true positive rate was 10%. Based on these test ordering patterns, we projected that 120 tests would be ordered in 2019, totaling >$200,000. Prior to the implementation of the algorithm in 2019, 55 tests were ordered, totaling $105,210. Total true positive rate was 3.6%. After implementation of the algorithm, 23 tests were ordered, totaling $50,220. The true positive rate was 13%.

Using a shared diagnostic stewardship approach, we were able to develop an evidence-based algorithm for guiding physicians for AE panel ordering. Comparing test ordering patterns pre and post-implementation in 2019, our true positive rate more than tripled (3.6% to 13%), indicating that our algorithm was able to successfully identify the at-risk population for development of AE disorders. This was met with a >50% decrease in the number of tests ordered, and a total cost savings of $54,990 compared to the first half of 2019.
Evidence for Age-Adjusted D-Dimer to Rule out Pulmonary Embolism: An Institutional Study
Authors: Balakrishnan Ridin , Casa Daniel , Gil Morayma Reyes
Published: October 2020

The diagnostic approach for ruling out suspected acute pulmonary embolism (PE) in the ED setting includes several tests: ultrasound, plasma d-dimer assays, ventilation-perfusion scans and computed tomography pulmonary angiography (CTPA). Importantly, a pretest probability scoring algorithm is highly recommended to triage high risk cases while also preventing unnecessary testing and harm to low/moderate risk patients. The d-dimer assay (both ELISA and immunoturbidometric) has been shown to be extremely sensitive to rule out PE in conjunction with clinical probability. In particularly, d-dimer testing is recommended for low/moderate risk patients, in whom a negative d-dimer essentially rules out PE sparing these patients from CTPA radiation exposure, longer hospital stay and anticoagulation. However, an unspecific increase in fibrin-degradation related products has been seen with increase in age, resulting in higher false positive rate in the older population. This study analyzed patient visits to the ED of a large academic institution for five years and looked at the relationship between d-dimer values, age and CTPA results to better understand the value of age-adjusted d-dimer cut-offs in ruling out PE in the older population. A total of 7660 ED visits had a CTPA done to rule out PE; out of which 1875 cases had a d-dimer done in conjunction with the CT and 5875 had only CTPA done. Out of the 1875 cases, 1591 had positive d-dimer results (>0.50 µg/ml (FEU)), of which 910 (57%) were from patients older than or equal to fifty years of age. In these older patients, 779 (86%) had a negative CT result. The following were the statistical measures of the d-dimer test before adjusting for age: sensitivity (98%), specificity (12%); negative predictive value (98%) and false positive rate (88%). After adjusting for age in people older than 50 years (d-dimer cut off = age/100), 138 patients eventually turned out to be d-dimer negative and every case but four had a CT result that was also negative for a PE. The four cases included two non-diagnostic results and two with subacute/chronic/subsegmental PE on imaging. None of these four patients were prescribed anticoagulation. The statistical measures of the d-dimer test after adjusting for age showed: sensitivity (96%), specificity (20%); negative predictive value (98%) and a decrease in the false positive rate (80%). Therefore, imaging could have been potentially avoided in 138/779 (18%) of the patients who were part of this older population and had eventual negative or not clinically significant findings on CTPA if age-adjusted d-dimers were used. This data very strongly advocates for the clinical usefulness of an age-adjusted cut-off of d-dimer to rule out PE.
Pregnancy-Related RBC Alloimmunization in Sickle Cell Trait Patients; A Single-Center Experience
Authors: Barouqa Mohammad , Castrodad-Rodriguez Carlos , Gil Morayma Reyes , Nelson Randin , Szymanski James , Paroder Monika
Published: October 2020

Background

Sickle Cell Disease (SCD) is an autosomal recessive disorder, which results from a point mutation in the Î²-globin gene. The production of mutant Hb S (V6E) leads to hemolytic anemia and numerous clinical complications. Patients homozygous for HbS gene (SS) typically rely on life-long transfusion therapy. Alloimmunization to foreign RBC antigens in multiply transfused patients is significantly more frequent in SS patients (observed in 7–47%) compared to patients with HbA (AA), and can pose a significant hurdle in finding compatible RBCs. However, the mechanism for enhanced alloimmunization in SS patients has not yet been elucidated. Patients heterozygous for HbS (SA) have a no distinct clinical phenotype and do not typically require transfusions. We investigated the rate of RBC antigen alloimmunization and specificity in SA patients.

Aim

The aim of this study was to determine and compare the rate and specificities of RBC antigen pregnancy-related alloimmunization in SA and AA patients.

Methods

In our retrospective study, we identified females who delivered a newborn between January 2014 to October 2019, for whom prenatal hemoglobin electrophoresis testing, and prenatal and perinatal antibody screening and identification was performed. R (V.3.6.2) statistical computing program was used for analysis.

Results

A total of 41735 subjects were identified: 40058 (AA) and 1677 (SA). African Americans were more prevalent in the SA compared to the AA group (55.8% vs 29.4%, P<0.01)and were more likely to have received ≥ 1 transfusion during pregnancy (4.5% vs 3.3%, P<0.01). A total number of 267 alloantibodies were detected in 246 patients (0.6% of the studied population) during pregnancy, 228 patients (0.6%) in the AA group and 18 patients (1.1%) in the SA group.229/246 (93%) of patients with antibodies did not receive transfusion during pregnancy, and thus antibodies were considered to represent pregnancy-related alloimmunization. In non-transfused subjects the SA group were more likely to have developed alloantibodies in pregnancy compared to the AA group [OR= 1.94, P=0.015]. The median age of patients with antibodies in the SA was older [33.5 vs 27 (p=0.008)] as compared to those in the AA group [29 vs 27 (p=0.002)].

The most common antibody identified was anti-E (SA 42% vs AA 28%), anti-Lea (SA 21% vs AA 13%) and anti-C (SA 5% vs AA 12%). Subjects with pre-existing alloantibodies had a 5.4x increased risk of forming a new allo-antibody. However only 0.1% of subjects had a history of prior allo-antibodies, with no significant difference identified between AA and SA.

Conclusions

SA patients were found to have an increased rate of pregnancy-related alloimmunization (OR 1.75, P=0.02) after adjusting for the effects of increasing age, RH type, ethnicity, number of previously existing antibodies and number of transfusions in pregnancy.
Symptomatic Cerebral Metastases In Malignant Pleural Mesothelioma: A Rare Case Report
Authors: Jadhav N C , Krasnozhen-Ratush O , Hicks R , Schapiro R
Published: October 2020

Casestudy: Malignant mesothelioma is an aggressive tumor with dismal prognosis. Incidence in the United States is approximately 3300 cases/year, and the most common site is the pleura. Although mesothelioma is usually a locally invasive tumor, distant metastases to liver, adrenal glands, kidney and contralateral lung have been described. Brain metastases are observed in less than 3% of metastatic cases and most have been detected incidentally at autopsy. Symptomatic brain metastases are unusual. We describe a case of a 77 year old gentleman with history of occupational asbestos exposure who presented with shortness of breath and dry cough. The radiological investigations revealed left pleural thickening with pleural effusion, which on biopsy proved to be biphasic malignant mesothelioma. Despite multi-modality therapy, the patient showed local disease progression. Following 37 months of initial diagnosis, he developed progressive left-sided weakness. Brain MRI revealed a 1.7 cm enhancing mass involving right posterior frontal lobe, with extensive edema in the surrounding tissue. On biopsy, mass was composed of nests and sheets of round-to-spindled cells with scant eosinophilic cytoplasm, separated by fibrous septa. Brisk mitotic activity and necrosis were present. There was a sharp border with adjacent brain parenchyma. The tumor was positive for WT-1, calretinin, and cytokeratins and negative for Ber-Ep4 and glial fibrillary acid protein by immunohistochemistry. The histological appearance of the tumor was similar to that of the pleural biopsy. Thus a diagnosis of metastatic malignant mesothelioma was made. This solitary metastasis was treated with resection and post-operative stereotactic radiation. The 3-month follow-up brain MRI revealed nodular enhancement within the cavity with multiple supra- and infra-tentorial enhancing lesions, and leptomeningeal enhancement, most consistent with progressing metastatic disease. With the advancements in treatment options that has improved survival in malignant mesothelioma patients, the pathologist and neurosurgeon should be aware of the diagnostic possibility intra-operatively which may alter the management.
Endometrioid Carcinoma with Hepatoid Differentiation: A Case Report and Comparison to Literature
Authors: Bowers K A , Johannesen E , Nguyen V
Published: October 2020

Introduction/Objective

High-risk endometrial carcinomas comprise only 15% of all uterine malignancies but are responsible for over 50% of deaths. Hepatoid malignancies of the endometrium (HME) are rare entities with a distinct morphology that is important to recognize because it is associated with rapid progression and high mortality.

Methods

We report a case of a HME and compare it to a collective review of 17 HME cases from the literature.

Results

A 61-year old female presented with post-menopausal bleeding and was diagnosed with endometrioid carcinoma with hepatoid differentiation. The hepatoid component was strongly positive for hepatocyte specific antigen (HepPar-1/OCH1E5). The entire tumor was negative for alpha-fetoprotein (AFP) and was negative for MLH-1 and PMS-2, indicating microsatellite instability. This is the first reported case of AFP-negative HME. HME unanimously present in the 6th decade or later with post-menopausal bleeding and elevated serum AFP. Histologically, hepatoid morphology is most commonly admixed with endometrial adenocarcinoma (56%) or carcinosarcomas (28%), but rare pure hepatoid carcinomas (11%) also occur. Hepatoid differentiation is often found in the myometrium, within vasculature, or lymph node metastases and is often positive for AFP and other hepatoid-markers (HepPar-1, Arginase-1, Glypican-3). Like hepatoid malignancies in other organs, HME have an aggressive clinical course. There was statistically significant (p = 0.046) difference between disease stages, with death from disease occurring in 12% of the stage I/II compared to 75% of the stage III/IV cases. Of those who died of disease, 71% had a survival of one year or less, often from early locoregional recurrence and/or lung metastases.

Conclusion

This case series is the largest review of HME to date and summarizes the features common to this rare, but histologically distinct, highly aggressive variant. This highlights the importance of thorough examination of uterine resections for variant histology as it is an important component of prognosis and treatment.
Cutaneous Eccrine Adenolipoma with a Spindle Cell Component
Authors: Karimi S S , Braniecki M , Bain M , Jetter N , Murray T
Published: October 2020

Introduction/Objective

Cutaneous adenolipoma is a rare, benign variant of solitary lipoma characterized by a mature adipocytic proliferation with entrapped eccrine or apocrine sweat glands. It is found predominately in middle-aged females, with a predilection for lower extremities including the thigh and gluteal regions. Cutaneous adenolipoma is presumed to be a hamartomatous process. Herein, we report a unique case of a cutaneous eccrine adenolipoma with a spindle cell component, namely, an early evolving spindle cell adenolipoma.

Methods

A 43-year-old female with a recurrent history of hidradenitis presented with a 2.7 cm x 1.5 cm x 0.7 cm soft, mobile nodule on the right posterior thigh. It had been present for at least four months and clinically resembled a lipoma. An excisional punch biopsy was performed for pathological evaluation. A concurrent nevus lipomatosus superficialis was diagnosed from the right perineum.

Results

Gross examination of the thigh nodule revealed fragments of a tan-yellow, lobulated, fatty lesion. Microscopic examination demonstrated a benign lipomatous proliferation with entrapped eccrine glands associated with a surrounding spindle cell stroma. Initial differential diagnosis included a cutaneous eccrine adenolipoma variant and a cutaneous mixed solitary hamartoma composed of admixed neural, eccrine and lipomatous components.

Immunohistochemical staining showed uptake for CD34 and CD10 in the spindle cell stromal component, but negative for desmin and S100. Based on our histopathological findings, our diagnosis of an eccrine cutaneous adenolipoma with a spindle cell component was rendered. This unique lesion displayed features of an evolving spindle cell lipoma with entrapped sweat glands, which may be viewed as an early stage of a dermal spindle cell adenolipoma.

Conclusion

Cutaneous eccrine adenolipoma is a rare, benign lipomatous neoplasm with entrapped sweat glands that can also show a spindle cell component. We share this rare lesion exemplifying the histomorphological spectrum of a lipomatous hamartoma and to highlight the recognition of a cutaneous adenolipoma.
Platy Talc, Asbestos, and Talc Fibers in the Female Genital Tract in Patients with Ovarian Cancer
Authors: McDonald S A , Godleski J J
Published: October 2020

Introduction/Objective

Recent analyses on human tissue help inform the discussion regarding talc and ovarian cancer, by showing that, in some patients, considerable talc can migrate to multiple organ sites in the pelvic region from perineal application. Recently, we showed that birefringent particles were seen by polarized light microscopy and shown to be talc by scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDS) and/or Raman spectroscopy in surgically resected tissues from patients with ovarian carcinoma and perineal talc exposure. These sites included ovary, cervix, fallopian tube, uterine serosa, and regional lymph nodes. Fibrous talc, with greater carcinogenic potential as determined by the International Agency for Research on Cancer, may be observed in pelvic tissues. Besides ascension through the reproductive tract, particles and fibers may gain entry to pelvic organs by accessing small submucosal lymphatics in the lower part of the tract. Both platy and fibrous talc have an Mg-Si elemental signature, weight % Mg/Si ratio within 5% of the theoretical value of 0.649, and thus are distinguishable from other exogenous substances including the various subtypes of asbestos.

Methods

Tissue-based analytic methods (including in situ SEM, where a paraffin block is examined directly under variable pressure) are critical in the detection of talc and asbestos, particularly since they preserve architecture, and demonstrate talc and/or fibrous particles within their histologic environment; this may help inform exposure origin and pathophysiologic significance.

Results

We reviewed the analytic outcomes of our consultative experience to date. This showed that 180 of 196 patients with a history of perineal talc exposure had birefringent particles seen by light microscopy in surgically resected pelvic tissues, and 82 of 91 had talc confirmed by SEM/EDS. Carcinogenic fibers were found in 28/82 (34%) of these patients, with talc fibers only (19/82 patients, 23%), asbestos (7/82, 9%) or both (2/82, 2%) confirmed by SEM/EDS.

Conclusion

Our study confirms that talc and toxic fibers may be found in human pelvic tissues of talc-exposed patients. Because the SEM/EDS method samples only a small amount of tissue relative to what is in the paraffin block, the finding of exogenous particles by this method typically translates to a high overall particle burden, when scaled mathematically to bulk tissue.
Metastatic Mucoepidermoid Carcinoma to the Pleura: An Unusual Presentation
Authors: Mashiana S S , Martinez Duarte E
Published: October 2020

Casestudy

Mucoepidermoid carcinoma is the most common malignant tumor arising in salivary glands. Predictors of poor prognosis include high-grade tumors, positive surgical margins, lymph node metastasis, or distant metastasis. The most common sites for distant metastasis include skin, lung, liver, and bone. We herein present a case of salivary gland mucoepidermoid carcinoma with pleural involvement, which is an infrequent site for metastasis. A 64-year-old female presented with worsening dyspnea and cough, which showed no improvement with antibiotics. Imaging showed a right lung nodule measuring 1.2 cm along with bilateral pleural effusion and pleural based nodularities. The dominant nodules in right and left chest measured 5.8 cm and 4.8 cm in greatest dimension, respectively. The findings were suspicious for metastatic disease. Cytological examination of pleural fluid showed reactive mesothelial cells and inflammatory cells. Subsequent biopsy of the right pleural nodule showed sheets of tumor cells with abundant eosinophilic cytoplasm and few scattered clear cells. Mucocytes were absent. The tumor cells were positive for p40 and negative for TTF-1 by immunohistochemistry. A review of patient’s medical history was significant for high-grade salivary gland mucoepidermoid carcinoma, which was resected and radiated six years prior. A comparison of both lesions showed similar morphologic features. Mucicarmine stain was positive in resection specimen but negative in pleural biopsy, confirming the absence of mucocytes. Molecular studies on both specimens showed positivity for fusion of CRTC1 (19p13) and MAML2 (11q21) loci. The overall findings were consistent with metastatic mucoepidermoid carcinoma to pleura.

Conclusion

Pleura is an uncommon site for metastasis from primary salivary gland mucoepidermoid carcinoma but should be part of differential diagnosis. Extensive review of patient’s past medical history plays a crucial role in correctly classifying these lesions as primary or metastatic. Differential diagnoses should include primary squamous cell carcinoma, mesothelioma, and the rare primary mucoepidermoid carcinoma of pleura.
Pulmonary Granuloma Associated with Pneumocystis Jirovecii in a Patient with Peripheral T-Cell Lymphoma: Presentation of a Rare Case with Review of the Literature
Authors: Aneja A , Arriola A , Jhala A
Published: October 2020

Casestudy: Although Pneumocystis jirovecii (PJ) is a known opportunistic pulmonary infection among immunocompromised patients, it is a rare (<5%) cause of pneumonia in this cohort. Majority of cases are observed in patients with HIV or solid organ transplant recipients. Granuloma formation in patients infected with PJ is even rarer. We present a case of multiple pulmonary granulomas associated with PJ in a non-HIV patient. A 49-year-old female with a history of asthma presented with worsening dyspnea. Initial imaging revealed multifocal bilateral areas of consolidation and a diagnostic bronchoalveolar lavage (BAL) demonstrated PJ organisms. Additional investigation was pursued to determine the etiology of this infection in a seemingly immunocompetent patient. New findings noted during hospitalization included a new maculopapular skin rash, significant weight loss, and lymphopenia. A bone marrow biopsy revealed a clonal proliferation of plasma cells. Subsequent imaging revealed mediastinal adenopathy. There was no improvement in symptoms despite treatment for pneumonia and a month later, a lung wedge biopsy revealed organizing acute lung injury and multiple non-caseating granulomas without lymphoid rimming, asteroid, or Schaumann bodies. Silver stain highlighted numerous PJ organisms within and outside of the granulomas. An inguinal lymph node and skin biopsies eventually revealed involvement by peripheral T-cell lymphoma (PTCL). Repeat BAL revealed clearance of organisms after additional therapy; however, the PTCL was refractory to chemotherapy and palliative care was pursued. To date, we could only find <30 cases of pulmonary PJ granulomas in patients with hematologic malignancies. Most are in patients with B cell lymphomas and just 1 report in a patient with adult T-cell leukemia/lymphoma. In summary, this case highlights that PJ associated pulmonary granulomas are uncommon, can be a harbinger of an underlying immunocompromised state, such as a lymphoma, and are even rarer to be associated with PTCL.
Toxic Adenoma Mimicking Papillary Thyroid Carcinoma
Authors: Aksionau A , Wei E
Published: October 2020

Introduction/Objective

A thyroid nodule requires multiple steps in the identification of its nature, which determines its management. In most cases, low TSH levels support a benign origin. However, examples of hyperfunctioning thyroid carcinoma have been reported. Recent observations show that the number of thyroid cancer increases with the prevalence in young patients. The ambiguity of some cases necessitates the use of a full range of diagnostic methods up to molecular cytological diagnostics.

Methods

We present a report on the case of an 11-year-old boy complaining of weight loss despite having a good appetite.

Results

The blood test showed free T4 1.51 (0.81 - 1.35 ng/dL), free T3 6.04 (3.31 - 4.88 pg/mL), and TSH 0.01 (0.662 - 3.90 mU/L). During sonography, the left thyroid lobe was almost completely replaced by an isoechogenic circumscribed mass with multiple colloid cystic spaces. No suspicious microcalcifications or abnormal cervical lymph nodes were identified. A thyroid scan revealed the presence of a toxic autonomously functioning thyroid nodule in the left lobe. Methimazole and propranolol were prescribed, with subsequent left hemithyroidectomy on 10/21/2019.

Grossly, the left thyroid lobe was 3.4 x 2.5 x 2 cm. The sectioning revealed light brown homogeneous stroma with a well-defined yellow-tan nodule (1.1 x 1.1 x 1 cm) in the middle of the lobe. The specimen was entirely submitted for permanent fixation in formalin. Microscopically, an encapsulated nodule was seen with the follicular and focal papillary pattern; nuclear features strongly and multifocally suggested a diagnosis of papillary carcinoma. HBME1 and calcitonin immunostains were negative; CK19 immunostain was multifocally positive. Next-generation sequencing supported the diagnosis of toxic adenoma with atypical features.

Conclusion

Every case of thyroid neoplasm should be fully investigated using modern and high-tech technologies, regardless of the functioning state of the gland. Molecular testing is supportive, especially in ambiguous situations, which benefits the patient.
Endobronchial Mucus Gland Adenoma: A Case Report
Authors: Sandhu A D , Liu Y
Published: October 2020

Introduction/Objective

Mucus Gland Adenoma (MGA) is a rare benign epithelial tumor with few case reports. They arise from submucosal glands and ducts of large proximal airways, but have been reported peripherally and within lung parenchyma. MGAs form an exophytic mass that causes obstructive symptoms, occurring in all ages without gender predilection. MGAs have low to no malignant potential, but may be confused with more aggressive entities. Thus, MGA may present a diagnostic challenge on frozen section.

Methods

We present the case of a 66-year-old male with recurrent right pneumonia and empyema. Bronchoscopy revealed an obstructing mass in the right bronchus intermedius. Biopsies and cytology were insufficient showing only benign bronchial epithelium. Therefore, the patient underwent surgical sleeve resection of the right bronchus intermedius for diagnosis and treatment.

It was received in two pieces measuring 1.0 x 0.6 x 0.5 and 2.0 x 1.5 x 0.9 cm - a well-circumscribed, firm white nodule with a smooth exterior and pushing borders. Cut surfaces were mucoid, homogenous and rubbery, with cysts measuring up to 2 mm. Histology showed crowded mucus-filled acini and tubules lined by bland cuboidal to columnar cells without atypia or mitosis. The stroma showed smooth muscle bundles and lymphocytic infiltrate. Benign bronchial epithelium lined the surface. A preliminary diagnosis of “adenoma” was made, with final classification pending permanent section.

Results

It showed positivity for s100, CK5/6, and CAM5.2. DOG1 showed a luminal staining pattern. NapsinA was negative and TTF-1 was patchy. P63, P40, CK5/6 and calponin highlighted myoepithelial cells, underlining the benign nature of the process.

Conclusion

MGA may resemble adenocarcinoma, low-grade mucoepidermoid carcinoma, and other benign adenomas. It presents a diagnostic challenge on frozen section as its malignant differentials are more common. Thus, it is important to recognize and be aware of these rare, benign tumors.
Concurrently Presenting Endometrial And Ovarian Endometrioid Adenocarcinomas- A Clinicopathologic Study Of 52 Cases
Authors: Lahori M , Borazan N
Published: October 2020

Introduction/Objective

Concurrent presentation of endometrioid adenocarcinomas in endometrium and ovary is uncommon, but oft-noted. They may arise from ovarian metastasis of endometrial carcinoma, endometrial metastasis of ovarian carcinoma, or synchronous development of independent primary lesions. Scully and Young criteria have been widely used to differentiate the site of origin.1 Role of a field effect in the genesis of synchronous carcinomas is supported by increasing evidence that endometrioid ovarian carcinomas arise from endometriosis. 2–5

Methods

All cases of concurrent endometrioid adenocarcinomas of the endometrium and ovary between 2002 and 2019 in the Mount Sinai health system New York were included, using pathology database (Powerpath) and EMR database (Epic).

Results

52 cases of concurrent endometrioid adenocarcinomas of endometrium and ovary were identified between 2002 and 2019. Mean age at presentation was 54.07 years (24–80). 69.2% had synchronous origin, 21.15% had endometrial primary and 3.8% had an ovarian primary. Ovarian endometriosis was identified in 51.9% and complex atypical hyperplasia in 26.9%. Lower uterine segment involvement was seen in 26.9%, bilateral ovarian involvement in 40.3%, fallopian tube involvement in 23% and lymphovascular space invasion in 25%. Different histologic grade of ovarian and endometrial counterparts was noted in 25% cases. Synchronous endometrioid carcinomas had the following characteristics: mean age at presentation 50.6 years, associated with CAH in 33.3% and endometriosis in 66.6%, presentation at stage 1 in 63.8% and lower grade of differentiation (grade 1/2) in 80.5% cases.

Conclusion

In majority of cases, synchronous endometrioid carcinomas have a younger mean age at presentation, are lower grade tumors, present at stage 1 and have associated endometriosis. It can be inferred that the percentage of synchronous tumors with endometriotic foci would be even higher (with extensive sampling & assuming that the neoplastic process has replaced native benign endometriotic foci) – pointing towards the likely role of endometriosis in the genesis of these tumors.
Impact of the Cholangiocarcinoma Component of Combined Hepatocellular/Hepatocholangiocarcinoma on Patient Survival
Authors: Gubbiotti M , Furth E E , Fortuna D , Tondon R , Karasic T
Published: October 2020

Introduction/Objective

The radiopathologic correlation, overall prognosis, and best management of combined hepatocellular carcinoma/cholangiocarcinoma (HCC/CC) remains uncharted territory.

Methods

We studied whether the percentage (%) of the cholangiocarcinoma (CC) component of HCC/CC impacted patient survival. A retrospective analysis was performed including all cases (18) of HCC/CC in the pathology archives from 2011–2019. Tumor beds were submitted entirely in all but 2 specimens, which were representatively sampled.

Slides from these cases were reviewed to assess % of CC. Survival was calculated from the date of diagnosis to the date of demise and censored as the date last known alive at the time of the study.

Results

13 cases were liver explants, 2 were resections, and 3 were biopsies. 13 cases were from clinical stage II patients, 2 were clinical stage IVA, and 2 were clinical stage IVB. All but one patient in the study group were males. There was no predilection for any specific tumor site. The cases were divided into three groups related to CC percentage: 0–20 (n=5), 21–40 (n=6), and >40% (n=7). AFP was variably elevated in select cases, with the highest values found in the medium and high % groups. Though there was no significant difference in overall survival among the three groups, mean and median survival trended in a downward fashion with increased % CC. Interestingly, radiology read 12 cases as HCC, 1 as intrahepatic CC, and only 1 as cholangiocarcinoma/hepatoma, atypical for HCC.

Conclusion

We conclude that there is a trend for decreased survival as % CC increases in combined HCC/CC patients, with patients with >20% CC tending to have lower survival rates. Furthermore, incongruity exists between radiologic and pathologic diagnoses of combined HCC/CC. Additional study with a larger sample size will yield more information to understand better prognosis as well as guide more accurate diagnosis of these patients.
Checkpoint Inhibitor Colitis Masked by Multi-drug Effect
Authors: Davis J W , Canevari M , Shaw J C
Published: October 2020

Casestudy: The utilization of checkpoint inhibitors such as programmed cell death protein 1 (PD-1/PD-L1) inhibitors (nivolumab) and cytotoxic T-lymphocyte antigen 4 inhibitors (ipilimumab) for treatment of certain malignancies has steadily gained popularity. Medication related colitis is uncommon, with a reported incidence of 1–9% depending on the checkpoint inhibitor used, and the histologic features have been characterized in recent literature. Because of the immunomodulating effect of these drugs, infectious colitis is in the differential diagnosis of enteritis. Multi-drug therapy in many of these patients further complicates identification of the culprit drug. We present the case of a 63-year-old male with metastatic renal cell carcinoma being treated with both nivolumab and ipilimumab who presented with acute on chronic non-bloody diarrhea. His clinical course was complicated by hypotension, acidosis and coagulopathy. The clinical differential for his colitis was cytomegalovirus infection versus a checkpoint inhibitor colitis. Colonoscopy revealed continuous circumferential loss of vascularity and diffuse erythema throughout the colon. Histology showed acute colitis with prominent apoptosis, cryptitis, crypt abscesses, and rare ringed mitotic figures, but without architectural distortion. Occasional smooth purple crystals consistent with pill material were present in the mucosa, but without significant tissue reaction. No pathogenic organisms were identified, and a cytomegalovirus immunostain was negative. These histologic findings in concert with the clinical history are consistent with checkpoint inhibitor colitis and multi-drug effect. A review of the patient’s chart showed cholestyramine was added to the patient’s regimen during hospitalization, which was consistent with the morphologic appearance of the crystals. Given the acute complications of checkpoint inhibitor induced enterocolitis and potential for increased morbidity (rare cases of bowel perforation and subsequent resection), accurate diagnosis is imperative. Management of checkpoint inhibitor associated colitis ranges from initiation of immunosuppression to checkpoint inhibitor cessation. When these findings are masked by multi-drug effect, accurate diagnosis can be difficult.
Squamous Cell Carcinoma Of Pancreas: An Exceedingly Rare Entity In A Young Female
Authors: Arshi J , Rao D
Published: October 2020

Introduction/Objective

Squamous cell carcinoma(SqCC) of Pancreas is a vanishingly rare neoplasm with dismal survival. Only a handful of cases are ever reported as pure SqCC reportedly accounts for <1% of malignancies of exocrine pancreas. Although, few theories have been proposed in an attempt to explain origin of this tumor including the possibility of (1)common progenitor cell and (2)squamous metaplasia, none have been proven with concrete evidence.

Methods

Here, we are presenting a case of squamous cell carcinoma of pancreas in a 33-year-old female who presented with 2-year history of right upper quadrant abdominal pain and a palpable mass. The imaging showed a multi-lobulated cystic mass encasing cystic duct, portal vein, and superior mesenteric artery.

Results

Grossly the mass was 5.2 cm in the greatest dimension. The mass revealed solid and cystic areas and was filled with hemorrhagic debris. On microscopy, the cyst wall was infiltrated by malignant neoplasm composed of irregular tongues and cords of malignant cells with nests of central keratinization. The tumor was consistent with squamous cell carcinoma. Foci of high grade cells with oval to spindled hyperchromatic nuclei, with many prominent nucleoli were also noted. There was no evidence of glandular component despite adequate sampling. The differential diagnoses of pancreatoblastoma and metastatic squamous cell carcinoma were considered and excluded.

Conclusion

SqCC of Pancreas is an exceedingly rare neoplasm of Pancreas. The diagnosis is made after extensive work up, adequate sampling and ruling out other common primary tumors and the possibility of metastasis. It usually follows an aggressive course with resistance to conventional neoadjuvant therapy. During the recent years, survival rates have shown some improvement with respectability and low to intermediate grade emerging as favorable prognostic factors. However, to further validate such findings noted in published case reports of this rare entity, collaborative studies with pooled data are deemed necessary.
A Rare Case Of Solid Pseudopapillary Neoplasm (Spn) Of Pancreas In A Male Patient
Authors: Arshi J , Rao D
Published: October 2020

Introduction/Objective

SPN is a rare neoplasm of the pancreas with low malignant potential and unknown histologic origin. It has a strong preponderance in young females (Female:Male ratio = 9:1).

Methods

We present a case of a 32-year-old morbidly obese male, who presented at our institution with an incidental large heterogeneous mass in the distal pancreas on imaging. Distal pancreatectomy with splenectomy was performed.

Results

Grossly, the mass measured 8 centimeters in greatest dimension with a tan-brown variegated cut surface.

The microscopic sections revealed a well-encapsulated tumor comprised of solid and cystic components. The solid areas show sheets and nests of hyalinized vascular stroma surrounded by small uniform cells with eosinophilic cytoplasm and bland round-to-ovoid nuclei. The immunohistochemical (IHC) stains showed variable positive expression with CD10, beta-catenin, and progesterone receptors. We also stained for newer putative IHC markers including LEF-1, TFE-3, SOX-11, and AMACR. Among them, LEF-1 was the only marker that showed 100% strong and diffuse, nuclear positive expression while the other three showed variable positive expression. These novel results are noted for the first time and is in congruence with the emerging molecular diagnostic finding that LEF-1 expresses the β-catenin binding domain of Wnt/β-catenin signaling pathway involved in the histologic origin of this tumor.

Conclusion

We present a rare case of SPN in a male patient. Additionally, this is the first case to report the staining pattern of newer putative markers of LEF-1, TFE-3, SOX-11, and AMACR that may suggest the pathobiology of histologic origin of this tumor.
Mistaken Identity: A Rare Tumor Unexpectedly Identified in a Renal Transplant Recipient’s Obsolescent Native Kidney
Authors: Ibrahim D , Dominiak N
Published: October 2020

Casestudy: Multilocular cystic clear cell renal cell neoplasm of low malignant potential is a rare entity, comprising 1–2% of all renal tumors. This is mostly due to that the majority (90%) are incidentally found by radiologic exams performed for other reasons. Cystic lesions are not uncommon in patients over 50 years old and are difficult to assess surgically. Therefore, it is even more important to recognize this subtype of renal cell neoplasm histopathologically, as these tumors behave very differently from their other counterparts. We report a case of a 63- year-old female renal transplant recipient who subsequently presented with bilateral native nephrolithiasis and left flank pain. Imaging demonstrated the calculi, for which the patient underwent left nephrectomy to relieve her pain. On gross examination, the cut surface of the kidney revealed a well-circumscribed, well-encapsulated, multiloculated cystic lesion at the upper pole measuring 1.9 cm with thin fibrous septae. Microscopically, the lesion was composed of loculations and septations as were observed grossly. These spaces were lined by one to two layers of cells with clear cytoplasm, some of which were present within the septal walls. The nuclei were haphazardly distributed within the cytoplasm of the cells. They were grade 2 according to the International Society of Urologic Pathology grading scale. The tumor cells demonstrated CK7 positivity. To our knowledge, this is the first case of multilocular cystic clear cell renal cell neoplasm of low malignant potential in a transplant recipient’s native end stage kidney mistaken for renal calculi.
A Rare Case of Retroperitoneal Isolated Enteric Duplication Cyst with Malignant Transformation
Authors: Alhamar M , Alkamachi B , Jaratli H , Shah R
Published: October 2020

Introduction/Objective

Isolated enteric duplication cysts (IEDC) are rare congenital abnormalities that do not have a communication with the normal intestinal lumen. They are usually recognized before the age of 2 years. They are rarely encountered in adults and very seldom undergo malignant change. These cysts are predominantly located within the abdominal cavity. They histologically demonstrate gastrointestinal mucosal lining and smooth muscle in the wall.

Methods

We report a case of a 45-year-old African American female who was evaluated for a pain in the left-sided abdomen and pelvis. Magnetic resonance imaging revealed a large multilocular cystic retroperitoneal mass, extending into the left iliac fossa and anteriorly displacing the colon. No other mass lesion was radiologically identified. The main radiologic impression was sarcoma. A biopsy was performed, and a pathologic diagnosis of adenocarcinoma was established with a consideration of primary retroperitoneal mucinous cystadenocarcinoma. An en bloc surgical resection of the retroperitoneal mass with adjacent segment of the descending colon was accomplished. Gross examination revealed an 11 x 5 x 4 cm cystic mass, containing a necrotic fluid and adherent to a 4 cm long segment of descending colon. Microscopically, the mass was lined by neoplastic cells arranged into tubules, villi and glands. Areas of necrosis were present. The wall of the cystic mass showed extensive hyalinized fibrosis and focal invasion. The neoplastic cells had positive immunoreactivity for CK7, CK20 and CDX2, but were negative for PAX8, PR and ER. Desmin immunostain and trichrome special stain highlighted a focus of smooth muscle bundle within the wall of the mass. These findings led to the pathologic diagnosis of adenocarcinoma arising in retroperitoneal IEDC.

Conclusion

In conclusion, we present this case because of its unusual presentation and location. Recognition of this entity and its rare malignant potential is important as it can pose a diagnostic challenge to pathologists.
A Case of Small-Cell Neuroendocrine Carcinoma of the Gallbladder in a Background of High-Grade Biliary Intraepithelial Neoplasia
Authors: Alkamachi B , Sharaf Aldeen B , Alhamar M , Jaratli H
Published: October 2020

Introduction/Objective

Neuroendocrine carcinoma (NEC) of the gallbladder is a very rare neoplasia comprising 4% of all malignant gallbladder neoplasms. Most of NECs show molecular accumulation of TP53, while KRAS mutations are rare. Approximately 40% of Biliary intraepithelial neoplasia (BilIN) cases are associated by KRAS mutations as an early molecular event, whereas TP53 mutation appears to be a late molecular event.

Methods

We report a case of a 62-year-old male who presented to emergency department for evaluation of abdominal pain associated with vomiting. Imaging studies demonstrated a distended gallbladder with small amount of pericholecystic fluid along with 5 mm calculus at the gallbladder neck consistent with symptomatic cholelithiasis and acute cholecystitis. No mass lesion was radiologically identified. A laparoscopic cholecystectomy was performed.

Grossly, there was a thickened area of mucosa at the distal body-fundus, measuring 5.0 x 4.5 cm. Multiple calculi were present. On histology, thickened area showed sheets and nests of moulded small cells with hyperchromatic nuclei, brisk mitotic activity and confluent necrosis. A diagnosis of small-cell NEC is established, and confirmed by positive immunoreactivity to neuroendocrine markers (CD56, Synaptophysin) and epithelial markers (CK7 and CAM5.2). Multiple foci of high-grade BilIN were noted. Subsequent entire submission of the gallbladder revealed no adenocarcinoma present. The pathologic stage was pT2a pNX.

Conclusion

In conclusion, this rare gallbladder carcinoma is found incidentally in a patient with acute cholecystitis symptoms and no clinical proof of mass lesion. In addition, there is a background of high-grade BilIN, which shares the molecular pathway of small-cell NEC. Therefore, awareness of such coexistence of these two pathologic entities in the same gallbladder, is essential to alert pathologists to look for the poorly-prognosis small cell NEC, whenever BilIN is encountered in random section of a gallbladder.
Pirfenidone Alleviates Features of Well-Established Chronic Pancreatitis in Mouse Models
Authors: Palathingal Bava E , Tarique M , Iyer S , Sahay P , Dawra R , Saluja A , Dudeja V
Published: October 2020

Introduction/Objective

Chronic pancreatitis (CP) is a fibro-inflammatory disease of pancreas with no targeted therapy and is considered irreversible. Antifibrotic agent pirfenidone is FDA approved for idiopathic pulmonary fibrosis.

However, exact molecular mechanism of its action is not clear. The aim of this study was to evaluate pirfenidone as a therapeutic agent for CP.

Methods

Caerulein-CP was induced in C57BL/6 mice by caerulein injections (50ug/kgx7, i.p., hourly x twice weekly x10 weeks). At 11 weeks, animals were randomized and assigned to either saline or pirfenidone group (400 mg/kg/d by oral gavage for 5 weeks). Mice were euthanized at 17 weeks. L-arginine induced CP was induced by i.p. injections of L-arginine (4.5g/kg x2 hourly, once a week x 4) and treatment was started after 5 weeks of start. Mice were sacrificed at early time-points after starting treatment. Single-cell suspension of pancreata were used for flow- cytometry. Pancreatic atrophy, histology, fibrosis and cytokine mRNA profile were evaluated. In vitro studies were done on stellate cells.

Results

The treated caerulein-CP mice had improvement in pancreas/mouse weight ratio, (7.03±0.41 vs. 4.75±0.28; p<0.0001). Histology scores and fibrosis markers were reduced. Pancreatic atrophy and histology scores showed significant improvement by day 14 of treatment in L-arginine CP. Flow cytometry showed that by day 7 of treatment there was significant reduction in macrophage infiltration (1.09 ± 0.18 % vs 3.26 ± 0.4 %; p<0.001) and pro-fibrotic M2 macrophage markers [IL-4 (1.5 ± 0.1 % vs 2.8 ± 0.2%; p=0.007)], while M1 marker (MHC II) did not change. mRNA levels of pro-inflammatory and pro-fibrotic cytokines decreased, and of anti-inflammatory cytokines increased. In vitro study on stellate cells showed reduction in mRNA levels of pro-fibrotic and pro-inflammatory cytokines as well as fibrosis markers in treatment group.

Conclusion

Pirfenidone ameliorates well-established CP in mouse models by altering immune cells.