bluuebunny/crossref_metadata_2025 huggingface dataset:
Stop Waiting for Tomorrow: Early Disk Diffusion—An Accurate Method for Antimicrobial Susceptibility Testing With Reduced Turnaround Time
Authors: Webber Daniel , Wallace Meghan , Burnham Carey-Ann
Published: September 2019

Background

Disk diffusion is a slow but reliable reference method for measuring antimicrobial susceptibility. Our objective was to improve the turnaround time for this method by reducing the culture incubation period prior to disk diffusion testing (referred to as early disk diffusion [eDD] testing).

Methods

Clinical isolates (n = 13) and quality control (QC) strains (n = 8) of bacteria, including 6 Staphylococcus aureus, 3 Enterococcus faecium, 3 Enterococcus faecalis, 3 Escherichia coli, 3 Pseudomonas aeruginosa, 2 Klebsiella pneumoniae, and 1 Enterobacter cloacae, were inoculated on blood agar by quadrant streaking and were incubated at 35○C for 6 hours (eDD6), 10 hours (eDD10), or 24 hours (standard [sDD]) before disk diffusion testing was set up in accordance with CLSI guidelines using Mueller Hinton Agar (Hardy Diagnostics) and clinically appropriate antimicrobial agents (total: 24). Experiments were performed sequentially in triplicate with zones measured by two independent readers.

Results

Examination of 6-hour blood agar plates showed limited growth in the first 1 to 2 quadrants while 10-hour growth plates had 4-quadrant growth and individual colonies in most cases. Despite limited growth on 6-hour plates, there were adequate bacteria to produce a 0.5 McFarland standard for disk diffusion testing for all 126 eDD replicates. Results were evaluable for 1,206 of 1,206 (100%) of eDD and 603 of 603 (100%) of standard disk diffusion (sDD). A comparison of early vs standard disk diffusion showed that eDD6 had 3 of 154 (1.9%) very major errors and 6 of 449 (1.3%) major errors, whereas eDD10 had no very major errors and 3 of 449 (0.7%) minor errors. Very major errors in eDD6 included a 1-mm difference between eDD6 and sDD for cefoxitin inhibition of S aureus as well as 4- and 6-mm differences between eDD6 replicates and sDD for nitrofurantoin inhibition of E cloacae. There was similar categorical agreement of eDD6 (96.7%) and eDD10 (96.7%) with sDD. Overall, there was a very good correlation of eDD6 (r2 = 0.98) and eDD10 (r2 = 0.99) with sDD. When grouping results by bacterial species, there was no more than 1-mm difference in median antimicrobial inhibition between eDD6, eDD10, and sDD. Of note, 5 of 7 bacterial species had the same median zone size when comparing eDD6 or eDD10 with sDD. There was also very little difference between early and standard methods when examining bacteria-drug combinations, with a similar zone size (difference in mode <2 mm) in 67 of 69 (97%) eDD6 and 66 of 69 (96%) eDD10 compared to sDD. Test results for QC isolates agreed with the CLSI recommended ranges in 97 of 99 (98%) eDD6, 97 of 99 (98%) eDD10, and 96 of 99 (97%) sDD.

Conclusion

Early disk diffusion testing is a simple and accurate method of antimicrobial susceptibility testing that can reduce time to results by as much as 18 hours with no additional cost.
Effect of Long-Term Storage on Hematopoietic Progenitor Cell Transplant Product Quality
Authors: Mattis Aidas , Sempek Diane , Thibodeaux Suzanne
Published: September 2019

Hematopoietic progenitor cell (HPC) transplant product quality indicators after prolonged cryopreservation are variable. A recent study in Europe demonstrated wide variability of cryopreservation times, from 1 to >20 years, with most centers storing products for 5 or 10 years. Thawed HPC viability using various ex vivo means and in vivo by studying neutrophil and platelet engraftment has generally supported preservation of CD34+ viability with prolonged storage. However, sample size, methods, and timepoints varied, and clear guidelines currently do not exist regarding how long HPCs can be stored. This study’s objectives include an evaluation of HPC quality indicators over time and if HPC product age and/or viability correlates with HPC engraftment. Retrospective record review was conducted on 837 HPC products thawed between January 1, 2011, and December 31, 2018. HPC products were sampled and characterized at thawing by flow cytometry for total nucleated cell (TNC) recovery, CD34+ recovery, and CD34+ viability (by 7-AAD). Preestablished acceptability criteria for TNC recovery, CD34+ recovery, and CD34+ viability were >80%, >40%, and >60%, respectively. If available, products with ANC engraftment data were further analyzed to correlate data with time to HPC engraftment. HPC products were stored between 3 and 5,943 days; 816 products were infused, ranging from 3 to 5,273 days in storage. Most (81%) HPC transplants occurred within the first year, 47 infusions occurred after storage >5 years, and 4 infusions occurred after storage >10 years. CD34 viability and percent recovery of TNC and CD34 were not significantly different as time in storage increased. Given sample paucity, 19 samples stored for >10 years were analyzed in individual years and grouped. In total, 96.5% samples stored for <1 year and 68% in samples stored >10 years met acceptability criteria for >60% CD34+ recovery; 98.9% samples stored <1 year met the >60% CD34+ viability acceptability threshold versus 90% of samples stored for >10 years. The oldest sample infused after storage of 5,273 days (14.4 years) showed 42% TNC recovery, 19% CD34+ recovery, and 84% CD34 viability; ANC engraftment data were not available. Sixty-five samples containing ANC engraftment data showed that time to ANC engraftment ranged from 9 to 15 days. No clear trend was present for viability or CD34 recovery when compared with days to engraftment based on limited data. Although rare, infusion of HPC products of extended duration occurs. This study suggests that HPC product quality may decrease after extended cryopreservation based on preestablished acceptability criteria. The oldest sample infused had preserved CD34+ viability despite significantly less TNC and CD34+ recovery, suggesting thawing might select for more robust HPCs. More studies with older samples are needed to determine the clinical impact of cryopreservation and if modification of current quality indicators could be useful clinically.
Evaluation of Positive T- and B-Cell Gene Rearrangement Studies Among Patients Without a Definitive Diagnosis by Other Assays
Authors: Mendoza Hadrian , Tormey Christopher , Siddon Alexa
Published: September 2019

In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-cell receptor (TCR) gene rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytogenetic studies. The significance of positive rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that gene rearrangement studies may be predictive of an emerging B- or T-cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR gene rearrangement testing at the authors’ affiliated VA hospital between January 1, 2013, and July 6, 2018, were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytogenetic characterization of the tissue source were recorded from pathology reports. Gene rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive gene rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 gene rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG gene rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false-positive IG/TCR gene rearrangement studies later developed a lymphoproliferative disorder, although 2 patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR gene rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR gene rearrangement results may not indicate the need for closer surveillance.
Performance of the Procalcitonin Test in Diagnosing Pneumonia in Real-World Practice
Authors: Ayala-Lopez Nadia , Ghaedi Mahboobe , Peaper David , Harb Roa
Published: September 2019

Background

Procalcitonin (PCT) rises early upon bacterial infection and has a long-half life, making it useful in the diagnosis of infections and antibiotic stewardship. We sought to determine the utility of PCT in diagnosing pneumonia (PNU) in the patient population presenting to our hospital during real-world clinical practice.

Methods

PCT results from patients in 2015 were reviewed retrospectively. Patients were eligible for inclusion if all of following criteria were met: PCT in 2015 and a lower respiratory tract culture, respiratory virus testing, chest x-ray, and white blood cell (WBC) count within 1 day of the PCT. Patients who opted out of research and those with mycobacterial infections and culture-positive infections of body sites other than urine and lower respiratory tract were excluded from further analysis.

Results

A total of 400 patients remained with 413 eligible PCT results across the ED (109), ICU (134), and inpatient (167) and outpatient (3) areas with a mean (SD) age of 66.2 (18.1). PCT was higher in patients with multiple pathogens reported on their respiratory cultures, direct fluorescence antibody (DFA), or PCR-based tests (mean ± SD = 2.43 ± 0.74 ng/mL; N = 32), than those with no pathogens reported (3.25 ± 1.13 ng/mL; N = 224; P < .05). Patients were grouped for the presence or absence of clinically defined PNU, according to a modification of the Centers for Disease Control (CDC) PNU1 criteria incorporating (1) chest x-ray results, (2) altered WBC number/altered mental status/fever, and (3) respiratory/breathing signs. PCT was higher in patients with clinically defined PNU, and the high PCTs were consistent with positive chest x-rays (criterion 1), and positive criterion 2 but not criterion 3. Incorporation of an elevated PCT >0.1 ng/mL into the PNU score slightly improved the area under the ROC curve (AUC) for the algorithm’s detection of PNU against the final clinical diagnosis (0.73 without PCT vs 0.76 with PCT). Furthermore, higher PCT was associated with higher 30-day and 1-year mortality.

Conclusion

PCT results were largely consistent with other markers of PNU such as imaging and CDC criterion 2, which suggests that PCT can be useful in evaluating for the presence of PNU. However, the PCT may not add additional information to assist in decision making above the already commonly ordered tests.
Alveolar Soft Part Sarcoma Presenting as a Uterine Polyp
Authors: Gomez Mariangela , Whiting Kerry
Published: September 2019

Background

Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor, mainly localized in the extremities, occurring principally in adolescents and young adults. ASPS is uncommon in the female genital tract.

Case report

We here report a case of ASPS in a 20-year-old nullipara, presenting with vaginal bleeding and profound anemia requiring blood transfusions. Ultrasonographic examination revealed a polyp in the lower uterine segment. Surgical resection of the polyp was performed, and pathological evaluation showed the typical histological, immunohistochemical, and molecular features consistent with ASPS. At the time of this report, the patient was scheduled for total hysterectomy with promising results.

Conclusion

Given the infrequency of ASPS, pathological evaluation is or utmost importance in order to establish an accurate diagnosis. When presenting as a primary tumor, complete excision is fundamental in the treatment.
Tumors With Neuroectodermal Differentiation of the Uterus and Ovary: A Series of 12 Cases and Review of the Literature
Authors: Ge Li , Zhou Amy , Maksem John , Gennette Sarah , Schimp Veronica
Published: September 2019

Objectives

Primitive neuroectodermal tumors (PNETs) are a group of small round cell tumors most commonly found in the central nervous system, soft tissue, or bone. Such tumors arising in the uterus or ovary are rare. In this study, we describe the clinicopathologic features from a series of gynecological tumors with neuroectodermal differentiation.

Methods

In a retrospective review, 5 years of departmental archives were searched for gynecological tumors diagnosed at Orlando Health’s Department of Pathology. Clinicopathological information was analyzed, including age at diagnosis, tumor size, depth of invasion, other component, pathologic stage, FIGO stage, immunohistochemical stains, months of follow-up, and current disease status.

Results

Twelve fully staged tumors with neuroectodermal differentiation were identified. Eleven were of uterine origin and one was of ovarian origin. Ages at diagnosis ranged from 38 to 78 years (median 65). Neuroectodermal component was variable in morphology, including lymphocyte-like small cells in sheets, perivascular pseudorosettes, or cords; larger cells with prominent nucleoli with or without cystic change; and giant cells resembling megakaryocytes. Components other than neuroectodermal differentiation included carcinosarcoma, dedifferentiated endometrioid carcinoma, and high-grade serous carcinoma. Membranous and/or paranuclear dot-like CD99 immunoreactivity were in all cases. Ten patients were deceased due to disease at 1 to 33 months follow-up, while one patient was alive without evidence of disease after 61 months follow-up, possibly due to being able to tolerate a different therapeutic protocol for peripheral PNET.

Conclusion

Neuroectodermal differentiation may be found as components of other gynecological tumors, especially those with an aggressive phenotype and high-stage disease. The neuroectodermal component comprises a spectrum of cytohistological features. Because of its presentation in the shadow of other components, it may be more common than is generally assumed. Mortality remains high, but recognition of neuroectodermal differentiation in gynecologic tumors might introduce a different therapeutic approach and potentially improve clinical outcomes.
Loss of WT1 Expression After Chemotherapy in a Primary Peritoneal Serous Carcinoma: A Case Report
Authors: De Los Reyes Francia Victoria
Published: September 2019

Objectives

Primary peritoneal serous carcinoma (PPSC) is defined as a high-grade malignant neoplasm with widespread peritoneal involvement in the setting of normal-sized ovaries that contain small surface tumoral implants and no other identifiable source of malignant serous neoplasm elsewhere in the gynecologic tract.

Methods

The aim of this case report is to contribute to the understanding of tumor immunophenotype and describe the behavior of a primary peritoneal serous carcinoma in relation to the conversion of the tumor’s WT1 immunohistochemistry expression from positive to negative after chemotherapy.

Results

This is a case of a 72-year-old female that presented with a history of increasing abdominal girth of 12 months. She underwent biopsy of the omentum and was diagnosed to have metastatic carcinoma that was positive for WT1, PAX8, CK7, and ER. The patient was initially diagnosed and managed as a case of ovarian serous carcinoma with metastasis to the omentum. She underwent neoadjuvant platinum-based chemotherapy and en-bloc total abdominal hysterectomy with bilateral salpingo-oophorectomy and low anterior resection, with metastasis resection. The criteria of PPSC were fulfilled due to the normal-sized ovaries and minimal ovarian involvement with normal fallopian tubes.

Immunohistochemistry of the resection specimen showed negative WT1 and PAX8, and positive ER, CK, and p16 expression, with null p53 expression.

Conclusion

Following the concept that WT1 expression portends a poorer prognosis, the loss of WT1 expression may be a positive response to the chemotherapy and should be correlated with the time to recurrence. The patient was noted to be recurrence free for 1 year and still does not show signs of the disease at present.

This is the first documented case of a previously WT1-positive primary peritoneal serous carcinoma that converted to a negative WT1 expression. This may provide insight on the role of chemotherapy in silencing protein expression.
Microcystic Stromal Tumor of the Ovary: A Case Report With Unique Histologic Features
Authors: Derakhshandeh Roshanak , Newsom Jonathan , Mneimneh Wadad , Carter Elliot
Published: September 2019

Objectives

Microcystic stromal tumor (MST) of the ovary is an extremely rare subtype of sex cord-stromal ovarian tumor with characteristic microcystic features and stromal tumor immunophenotype. First described as a distinct ovarian neoplasm in 2009, fewer than 30 cases of MST have been reported worldwide.

Methods

We present a 65-year-old patient who underwent a hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma and an enlarged right ovary detected by an abdominal CT scan.

Results

Grossly, the 3.6-cm ovarian mass had a smooth, firm external surface and clear demarcation from the adjacent ovarian parenchyma. Sectioning of the mass revealed solid, tan-white cut surfaces. The gross appearance of the contralateral ovary was unremarkable. Microscopic examination of the hysterectomy specimen confirmed FIGO grade 1 endometrial adenocarcinoma, endometrioid type. Stromal hyperthecosis was present in both ovaries. Unique to our case, the ovarian mass was composed of a prominent hyalinized fibrous stroma with occasional scattered nodules of small to medium cells with vacuolated cytoplasm, bland chromatin, inconspicuous nucleoli, and sparse mitotic activity. Characteristic microcystic spaces were present. The cells within these microcystic nodules were positive for β-catenin (nuclear), CD10 (membranous), and cyclin D1 (nuclear). Immunohistochemical stains for calretinin, CD56, CD99, cytokeratin AE1/AE3, EMA, inhibin, and WT-1 were negative.

Conclusion

The combined histologic and immunohistochemical properties of this tumor are most consistent with MST of the ovary. While the clinical behavior of this new entity appears to be benign, reported cases are limited and further investigation is needed. This report highlights a histologically unique case of MST of the ovary.
Tumor-Infiltrating Lymphocytes and Programmed Death-Ligand 1 Expression in Salivary Duct Carcinoma
Authors: Chatzopoulos Kyriakos , Collins Andrea , Garcia Joaquin
Published: September 2019

Objectives

Salivary duct carcinoma is a rare high-grade salivary gland tumor, sharing common features with invasive ductal carcinoma of the breast—particularly apocrine type. Increased density of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in many solid tumors and has been correlated with elevated expression of programmed death-ligand 1 (PD-L1), a targetable molecule. We investigated the prognostic role of TILs and PD-L1 expression in salivary duct carcinoma.

Methods

Clinical records and archived surgical pathology material were evaluated from 28 patients with a diagnosis of salivary duct carcinoma at Mayo Clinic Rochester (between 1961 and 2007). TILs were evaluated on hematoxylin and eosin–stained slides and reported as continuous variables. Immunohistochemistry for PD-L1 (clone 22C3) was performed on unstained slides and evaluated using the Combined Positive Score (CPS). Fisher’s exact test was used to assess frequency distribution differences. Log-rank test and Cox proportional hazards model were used to assess the impact of the variables on survival.

Results

Twenty-eight patients had salivary duct carcinoma (age range 35-87, mean 61), and follow-up averaged 60 months (range 6-252 months). At the end of the follow-up period, 22 patients (79%) had died of salivary duct carcinoma, while remaining patients were alive (4.14%) or had died of other causes (2.7%). For the entire follow-up period, levels of TILs of 40% or more were associated with favorable overall survival (log-rank test, P = .01) and were predictors of better survival in univariate analysis (hazard ratio: 0.18, P = .02). PD-L1 expression was not significantly different between the high and low TIL groups (Fisher’s exact test, P = .67). Survival analysis regarding PD-L1 expression did not yield statistically significant results (log-rank test, P = .74; hazard ratio: 0.87, P = .74).

Conclusion

High TIL levels, but not PD-L1 expression as determined using the CPS, predict better survival in patients with salivary duct carcinoma.
Primary Smooth Muscle Tumor of Breast: An Unusual Case Presentation
Authors: Liu S Shawn , Patel Krutika , Dyess Donna Lynn , Kahn Andrea
Published: September 2019

Introduction

Primary smooth muscle tumors (SMT) of the breast are rare with leiomyosarcomas representing less than 0.1% of all malignant breast tumors.

Case Presentation

A 58-year-old female with no significant past medical history noted on screening mammography to have a circumscribed 6-mm nodule in the right breast, upper outer quadrant. Core needle biopsy showed a spindle cell neoplasm with smooth muscle differentiation. The excisional biopsy showed a 6-mm lesion composed of atypical hyperchromatic spindle cells in fascicles, marked nuclear pleomorphism, and 5 mitoses per 10 high-power fields. By immunohistochemistry, the spindle cells were positive for smooth muscle actin, desmin, and negative for S-100 and cytokeratin AE1/AE3. Positron emission tomography/computed tomography of head/neck, chest, abdomen, and pelvis did not identify other neoplasms. Despite the lesion size, findings were supportive of a leiomyosarcoma.

Discussion

Breast SMTs have nonspecific clinical or imaging features. Histologically, these present as spindle cell tumors with smooth muscle differentiation. Initial workup starts with distinction between benign and malignant neoplasms. The malignant SMTs are usually large tumors with cytologic atypia and mitotic activity used as diagnostic criteria. In addition, the distinction between primary and metastasis is important and frequently relies on clinical history and exclusion of other primary origins by radiographic survey. In the current case, although the tumor size is unusually small, the histological features and absence of other primary malignancies support the diagnosis of a leiomyosarcoma.

Conclusion

Primary leiomyosarcoma of breast is extremely uncommon with less than 70 cases reported in the literature. Although they are usually large tumors, this diagnosis should be included in the differential diagnosis when smooth muscle differentiation, significant atypia, and mitoses are encountered in a spindle cell tumor of the breast.
Lipomatous Metaplasia of the Thyroid Gland: A Clinicopathologic Review
Authors: Solarewicz Joanna , Reddy Vijaya , Bitterman Pincas , Ghai Ritu , Gattuso Paolo
Published: September 2019

Objectives

Lipomatous metaplasia involving the thyroid gland is uncommon in surgical pathology and the majority of published literature is confined to single case reports. We undertook a retrospective study to assess the frequency of fat metaplasia among benign and neoplastic thyroid lesions.

Methods

Surgical pathology files from 1992 to 2018 at our institution were searched for lipomatous metaplasia involving the thyroid gland. A total of 2,018 cases of thyroid lesions after lobectomy or total thyroidectomy with or without regional lymph node sampling were identified. Patient clinical and pathologic data were reviewed.

Results

The 2,018 thyroid cases reviewed included 828 papillary carcinomas, 33 medullary carcinomas, 26 anaplastic carcinomas, 25 follicular carcinomas, 262 follicular adenomas, 422 goiters, 373 Hashimoto thyroiditis, and 49 Grave disease. Lipomatous metaplasia was recorded in 17 cases (0.8%), which included 8 males and 9 females with a mean age of 67 years (range: 55 to 82). The most common lesion containing fat metaplasia was goiter (7/422 cases, 1.7%), followed by follicular adenoma (4/262, 1.5%), papillary carcinoma (4/828, 0.5%), Hashimoto thyroiditis (1/373, 0.3%), and Grave disease (1/49, 2%). When associated with papillary carcinoma, lipomatous metaplasia was located in the surrounding benign thyroid tissue in 2/4 cases and in malignant papillary structures metastatic to neck lymph nodes in the remaining 2/4 cases.

Conclusion

Lipomatous metaplasia of the thyroid gland is a rare phenomenon, present in only 17/2,018 cases (0.8%) in our study. It was more commonly seen in reactive processes (9/844 cases, 1.1%) and follicular adenomas (4/262 cases, 1.5%). Among the 912 cases of malignant tumors, fat metaplasia was only identified in papillary carcinoma (4/828, 0.5%), half of which showed metaplasia at the metastatic site. The presence of lipomatous metaplasia in reactive as well as neoplastic lesions cannot be used as a reliable histologic feature to exclude a neoplastic process.
A Rare Case of Hermansky-Pudlak Syndrome Involving Bilateral Lung: Histopathologic and Electron Microscopic Findings
Authors: Basu Atreyee , Seshan Surya , Angel Luis , Moreira Andre , Zhou Fang
Published: September 2019

Introduction

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive hereditary disorder characterized by oculocutaneous albinism and bleeding diathesis. Transplantation is often conducted to treat lung fibrosis, which is the most fatal complication of this disease. While the literature discusses the diagnosis of HPS based on genetic testing, radiology, and electron microscopic (EM) findings of platelet granules, there is a paucity of images in the literature illustrating the pulmonary histopathologic and EM features of HPS.

Case Report

Here we present striking histopathologic and EM images from a case of pulmonary fibrosis due to HPS in a 48-year-old female. The patient presented with restrictive lung disease and bilateral decreased breath sounds with diffuse crackles. She was clinically diagnosed with HPS and underwent bilateral lung transplant. On histopathology, both pneumonectomy specimens showed diffuse interstitial fibrosing and cellular pneumonitis with end-stage remodeling and type II pneumocyte (PC-II) hyperplasia. The PC-IIs had abundant foamy cytoplasm and compressed scalloped nuclei. Alveolar macrophages contained fine brown granules positive for PAS-D stain. EM analysis revealed that the PC-IIs contained numerous lamellated myelin bodies (so-called giant lamellar body degeneration) suggestive of surfactant admixed with lipid and luminal microvilli. The pigmented alveolar macrophages also contained lamellated myelin bodies, as well as clusters of single membrane-bound structures with varying size and electron density admixed with vacuolar and granular debris suggestive of ceroid deposits.

Conclusion

Based on light microscopy, histochemical analysis, EM, and clinical presentation, it was concluded that our findings were consistent with pulmonary changes as seen in HPS.
A Rare Epithelioid Sarcoma of the Jaw Mimicking Pleomorphic Rhabdomyosarcoma: Case Report and Literature Review
Authors: Brown Tupokigwe , Mlaga Salvatory , Vuhahula Edda
Published: September 2019

Background

Epithelioid sarcoma, a rare soft tissue malignancy, is clinically aggressive and commonly affects distal extremities. Proximal, fibroma-like, and angiomatoid variants are lightly outlined. The proximal variant is the most aggressive, composed of larger cells and rhabdoid features, characteristically captivating one’s attention to rhabdomyosarcoma. We present a rare epithelioid sarcoma that histologically mimicked pleomorphic rhabdomyosarcoma of jaw in a 31-year-old male.

Objectives

To discuss histopathological features of epithelioid sarcoma of rhabdoid features, distinguishing it from other histological mimics like rhabdomyosarcoma.

Methods

A 31-year-old male was admitted at Muhimbili National Hospital in October 2017 with a 4-month history of slow-growing tender ulcer on the lower right jaw and right-side facial swelling. Clinical impression was squamous cell carcinoma with differential of adenocarcinoma. Various laboratory investigations, imaging, routine staining, and immunohistochemistry were performed.

Results

CT scan revealed a heterogenous mass in the right submandibular region. Initial examination from incision biopsy showed large oval pleomorphic tumor cells with enlarged vesicular nuclei and abnormal mitoses. Wide excision biopsy followed after conclusion of poorly differentiated carcinoma. Its examination revealed a diffuse, nodular tumor with large, polygonal, round, spindle cells displaying abundant deeply eosinophilic cytoplasm, sometimes showing eccentric vesicular nuclei. Rhabdoid features were observed. Immunohistochemistry revealed strong positivity for wide-spectrum cytokeratin, vimentin, and CD99 and was negative for EMA and myogenin.

Conclusion

Morphology by routine stains suggested both epithelial and mesenchymal malignancy. Cells with rhabdoid features suggested pleomorphic rhabdomyosarcoma with differential of epithelioid sarcoma. Cytokeratin, vimentin, and CD99 confirmed the diagnosis of epithelioid sarcoma, proximal variant. This case adds information on this rare entity emphasizing application of diagnostic immunohistochemistry procedures in the platform for confirmation of diagnosis to assist in proper patient management.
Leiomyosarcoma: A Rare Tumor of the Vulva
Authors: Sameeta Fnu , Haque Monira , Akbar Shalla , Zotto Valeria Dal , Kahn Andrea
Published: September 2019

Objective

Primary sarcomas of the vulva are very rare malignancies, accounting for 1% to 3% of all gynecologic sarcomas. Leiomyosarcoma is the most common histologic type. They present with nonspecific symptoms, aggressive behavior, and high metastatic potential.

Methods

A 63-year-old female patient presented with a 6-month history of a slow-growing, painless vulvar mass at the right posterior fourchette. CT scan revealed an asymmetric, heterogeneous vulvar mass extending to the distal vagina, without lymphadenopathy or evidence of distant metastasis. Focal prominence of the uterus suggestive of leiomyoma was also noted, but primary uterine neoplasm with vulvar metastasis could not be excluded. The patient underwent wide local excision of the vulvar mass with hysterectomy and bilateral salpingo-oophorectomy.

Results

Gross examination of the vulvar specimen showed an ulcerated 2.1-cm solid white mass with irregular borders. Microscopically, the vulvar tumor consisted of a focally infiltrative spindle and pleomorphic neoplastic proliferation with interlacing fascicular pattern and increased mitotic activity up to 25/10 HPF, without necrosis or lymphovascular invasion. The tumor focally extended to resection margins. Immunohistochemically, the neoplastic cells were positive for SMA, ER, and desmin and negative for S-100 and cytokeratin AE1/AE3. These findings, in conjunction with the clinical presentation, were consistent with high-grade primary vulvar leiomyosarcoma. Radiation therapy was subsequently started.

Conclusion

Primary vulvar leiomyosarcomas are rare and secondary involvement by uterine primary should always be ruled out. In addition, these tumors can be mistaken clinically as benign processes such as Bartholin gland cysts, infectious granuloma, fibroma, or myoma. Hence, it is vital to consider vulvar sarcomas in the differential diagnosis of nonspecific vulvar lesions in order to avoid delay in diagnosis and treatment. The rarity of this diagnosis makes this case worth reporting.
Primary Mucinous Adenocarcinoma: The Critical Role of Morphology in a Rare Neoplasm
Authors: Williams Michael , de la Roza Gustavo
Published: September 2019

Objectives

Primary mucinous adenocarcinoma of the skin is a rare clinical entity derived primarily from sweat glands with reported sites mainly arising from the head and neck region. Difficulty then arises with distinguishing between these primary neoplasms and those with similar morphology in the breast and/or gastrointestinal tract.

Presentation of Case

We report a case of an 85-year-old female with a past medical history of endometrial cancer presenting to clinic with a slow-growing right temporal lesion that was excised and diagnosed as primary mucinous adenocarcinoma. Further clinical workup and imaging revealed an oral lesion diagnosed as squamous cell carcinoma after excision along with an enhancing right breast mass with biopsy and excision showing an invasive ductal carcinoma with papillary and micropapillary features. This unusual presentation of more than two malignancies provides a challenge to differentiate between primary versus metastatic disease, especially with a rare malignancy that is present.

Discussion

A review of the literature on primary mucinous adenocarcinoma of the skin is presented, discussing epidemiology, clinical presentation, morphology, and immunohistochemistry sets historically studied to aid in diagnosis, with our case relying on morphology to finalize our diagnosis.

Conclusion

This unusual case highlights the difficulty in differentiating between primary versus metastatic mucinous adenocarcinoma yet highlights the value of morphology to aid in arriving at a diagnosis to help guide correct clinical treatment and follow-up.
Characterization of an Unusually Aggressive Ovarian Malignant Sex Cord Stromal Tumor in an Adolescent Female With Peutz-Jeghers Syndrome
Authors: Benzi Eduardo , Patil Ninad
Published: September 2019

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder with mutations in SKT11 (19p13.3), mucocutaneous hyperpigmentation, gastrointestinal hamartomatous polyposis, and increased cancer predisposition. A PJS-associated distinctive ovarian tumor is sex cord tumor with annular tubules (SCTAT), which is multifocal, microscopic, bilateral, and almost always clinically benign. Non-SCTAT ovarian tumors with malignant behavior are exceptionally rare. We describe a malignant, multiply recurrent, widely metastatic sex cord stromal tumor in PJS.

Case Report: A 17-year-old female presented with new complaints of unintentional weight loss, alopecia, and abdominal fullness. She had a PJS diagnosis at age 7 with mucocutaneous pigmentation, gastrointestinal polyposis, and STK11 mutation. CT showed a 23-cm abdominopelvic mass with diffuse peritoneal metastases and malignant pleural effusion. CA-125 was elevated. CEA, CA 19-9, β-hCG, AFP, and LDH were normal. Laparoscopic biopsy pathology revealed a tumor composed of sheets and loose aggregates of mitotic spindled and round heterogenous eosinophilic and basophilic cells within fibromyxoid stroma. Rare tubules with eosinophilic cytoplasm and focal foamy cells were also seen. IHC was significant for inhibin, calretinin, CD56 and WT1 positivity, and cytokeratin and EMA negativity, consistent with poorly differentiated sex cord stromal tumor. Interestingly, EM showed neurosecretory dense core granules and neurite-like processes. After neoadjuvant therapy, the resected left adnexal mass was 25.5 cm, purple-gray/tan-red, heterogeneous, diffusely cystic, diffusely edematous, rubbery to spongy. In the left ovary were also found unassociated microscopic SCTAT foci. During adjuvant chemotherapy, the patient became pregnant. During the pregnancy, the patient developed liver and pelvic peritoneal recurrence and continued altered chemotherapy. She delivered a healthy late-preterm infant but also concurrently had diffuse peritoneal recurrence. She underwent two more cycles of adjuvant chemotherapy. Approximately 2 years after finishing adjuvant chemotherapy, she again developed peritoneal recurrences, which were resected, and partial chemotherapy response was seen on pathology. She is currently undergoing additional chemotherapy cycles 4 years since the initial diagnosis.
Lymphangioleiomyomatosis and Micronodular Pneumocyte Hyperplasia in a Patient With Tuberous Sclerosis Complex
Authors: Peter An , Aneja Amandeep
Published: September 2019

Lymphangioleiomyomatosis (LAM) is a rare progressive disease characterized by proliferation of smooth muscle–like cells in the lung, mediastinum, and abdomen. In the lung, it is seen with cystic destruction of the lung parenchyma, which occurs almost exclusively in premenopausal women. It occurs in about 1% of patients with tuberous sclerosis complex (TSC). MNPH is an extremely rare pulmonary manifestation of TSC, comprising type 2 pneumocytes in a pattern resembling bronchioloalveolar adenocarcinoma. We report a case of both pulmonary LAM and MNPH associated with TSC. A 35-year-old female with a past medical history of TSC with multiple complications was admitted with iatrogenic pneumothorax following nasopharyngeal intubation during a dental procedure. A blebectomy with wedge resection and mechanical pleurodesis was performed. On gross examination, the wedge specimens revealed multiple cysts in a random distribution. Microscopic examination of the lung parenchyma revealed prominent smooth muscle cells with focal nodule formation. Immunohistochemical stains for SMA and HMB-45 were found to be positive and corroborated these findings. Areas of localized nodular proliferation of benign cuboidal type II pneumocytes lining alveolar walls were also identified. These findings are consistent with LAM and MNPH. Clinicopathological correlation with surgical investigation is indispensable in diagnosing LAM and MNPH, especially when radiologic findings are not definitive in these entities.
How Does Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Compare to Encapsulated and Nonencapsulated Follicular Variants of Papillary Thyroid Carcinoma? An Examination Into Next-Generation Sequencing Molecular Profiles
Authors: Serrano Antonio , Sun Wei , Liu Cheng , Simsir Aylin , Cangiarella Joan , Brandler Tamar
Published: September 2019

Objectives

With the removal of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) from the follicular variant of papillary thyroid carcinoma (FVPTC) categorization, the question arises as to how the molecular profile of invasive encapsulated FVPTC (IEFVPTC) compares with NIFTP. Our study aimed to examine the molecular alterations associated with NIFTP, IEFVPTC, and infiltrative FVPTC (iFVPTC) to determine whether these entities are actually distinct at the molecular level.

Methods

Forty-five NIFTP cases, 12 IEFVPTC cases, and 8 iFVPTC cases from 1/2013 to 8/2016 were assessed for presurgical fine-needle aspiration ThyroSeq V2 next-generation sequencing results.

Results

The NIFTP cases displayed alterations in BRAF K601E/EIF1AX, BRAF T599_R603, NRAS x15 (two with additional PTEN and one with P53), KRAS x3, HRAS x11 (one with an additional TERT/EIF1AX), PAX8-PPARgamma x5, PTEN, THADA x3, MET x2, copy number alteration, EF1AX, and DICER1. The IEFVPTC displayed alterations in RAS x5 (1 NRAS/TERT, 2 HRAS, 2 NRAS), BRAF-K601E x2, and BRAF-pG469A with gene expression profile; PAX8-PPARgamma x2; THADA-IGF2BP3; and ETV6/NTRK3. The iFVPTC cases displayed alterations in RAS x2 (NRAS and HRAS), TERT x2, BRAF-V600E mutation, ALK, MET, and NTRK3.

Conclusion

NIFTP and IEFVPTC cases most commonly displayed RAS mutations (64.4% and 41.7%, respectively) and lacked aggressive BRAF-V600E mutations, whereas iFVPTC harbored aggressive mutations such as BRAF-V600E and TERT more commonly, with fewer RAS mutations. The possibility of NIFTP and IEFVPTC being on a premalignant to malignant continuum must be raised and these entities may be more similar to each other than to other entities such as iFVPTC.
Vascular Pseudoinvasion: A Case Report and Review of Literature
Authors: Agarwal Anupma , Wu Hueizhi
Published: September 2019

In the era of minimally invasive procedures, laparoscopic hysterectomy is preferred over total abdominal hysterectomy as the primary treatment of endometrioid cancer limited to the uterus. Lymphovascular invasion (LVSI) is an important prognostic indicator for this tumor. Studies have observed presence of vascular pseudoinvasion in the surgical specimen excised via laparoscopic hysterectomy. Some studies have reported no increase in LVSI after minimally invasive surgery, implying that there is no vascular pseudoinvasion. Here, we present a 59-year-old female with history of obesity, hypertension, diabetes mellitus, asthma, and biopsy-proven well-differentiated endometrioid adenocarcinoma who underwent total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and sentinel node dissection. An ill-defined friable mass (2.1 cm in maximum dimension) was present in the posterior lower uterine segment and had the morphology of endometrioid adenocarcinoma, grade 1 out of 3, invasive into the outer half of myometrium. There was no true vessel invasion but rather abundant contamination—smearing of tumor into vascular spaces. An immunostain for D2-40 identified no lymphatic invasion. Immunostains for CD31 and CD34 highlighted tumor cells present in vascular spaces consistent with pseudoinvasion. No regional lymph node metastasis was seen. Peritoneal fluid did not show malignant cells. After surgery, the patient received radiotherapy and had no evidence of recurrent disease. It has been proposed that the artifact of vascular invasion as seen in our case could be associated with the technique of laparoscopic hysterectomy. Substantial LVSI, in contrast to focal or no LVSI, has been shown to be the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis, and overall survival. Its presence is a deciding factor for the type of adjuvant therapy. Therefore, it is important to recognize vascular pseudoinvasion to avoid misdiagnosis of LVSI.
Parasitic Leiomyoma After Laparoscopic Total Hysterectomy and Bilateral Salpingo-Oophorectomy, a Mimicker of Pelvic Neoplasm
Authors: Song Weihua , Asuzu Ifeyinwa , Villanueva Jocelyn
Published: September 2019

Parasitic leiomyomas are rare occurrences that may mimic malignancy and thus present a diagnostic dilemma. They are thought to arise from a pedunculated subserosal leiomyoma that undergoes torsion and detaches from the uterus, surviving by revascularization from adjacent structures, or from iatrogenic implantation during surgery, more common with the clinical popularity of laparoscopic surgery and power morcellation. We report a case of parasitic leiomyoma with degenerative changes in a 57-year-old female who was initially found to have a 6.5-cm left adnexal mass and multiple submucosal and intramural masses consistent with leiomyoma by abdominal pelvic computerized tomography test (CT) 7 years prior to presentation. She experienced severe abdominal discomfort that persisted after total abdominal hysterectomy and a 7.8-cm mass was found in the left pelvic cavity on reevaluation. Grossly, the pelvic mass was a 6.5-cm tan-gray ovoid firm mass with a 4.0-cm cystic cavity. The cut surfaces of the solid areas/cyst wall were gray-white and firm with focal yellow streaks. Microscopically, there was central cystic degeneration, with cyst wall showing extensive granulation tissue. The solid portion also showed extensive hyaline degeneration, fibrosis, and perinodular hydropic degeneration. Smooth muscle differentiation was evident at the periphery of the mass, confirmed by strong staining with desmin and smooth muscle actin. This represents a parasitic leiomyoma left behind following the first procedure and it developed degenerative changes. In addition to the high index of suspicion for malignancy in assessing adnexal masses, degenerating parasitic leiomyomas should be included in the differential diagnosis of such mass lesions.
Mcl-1 Expression May Be Associated With Favorable Clinical Outcome in BRAF V600E–Mutated MMR-Deficient Colorectal Cancers
Authors: Zhang Xin , Findeis-Hosey Jennifer , Sharma Meenal , Gonzalez Raul , Amorese Rebecca , Gupta Elena , Foor-Pessin Caitlin , Frado Laura , Marino Danielle , DeCross Arthur , Yang Qi , Hiroshige Karina , Huber Aaron
Published: September 2019

Objectives

The BRAF V600E mutation is associated with treatment resistance and is a poor prognostic indicator in colorectal adenocarcinomas (CRAs). Prior studies have shown that the BRAF V600E mutation confers resistance to apoptosis by Mcl-1 gene upregulation. We evaluated the clinical effect of Mcl-1 expression on BRAF-mutated (BM) MMR-deficient (dMMR) CRAs.

Methods

Thirty-one BM dMMR CRAs were included in a tissue microarray. The intensity and extent of Mcl-1 expression were evaluated by immunohistochemistry. Staining intensity (0-3+) and percentage of cells with positive staining (none, <10% = 1, 10%-50% = 2, and >50% = 3) were determined. Cases were considered positive when the intensity score multiplied by the percentage category score was >4. Mcl-1 expression was correlated with clinicopathologic features.

Results

Positive Mcl-1 staining was identified in 13 (42%), among which 9 (69.2%) were well to moderately differentiated with lymphovascular invasion present in 4 (30.8%), lymph nodes metastases in 3 (23.1%), and AJCC stage pT3 or greater in 8 (61.5%). In contrast, 18 (58%) were Mcl-1 negative, among which 10 (55.6%) were poorly differentiated with lymphovascular invasion present in 12 (66.7%), lymph node metastases in 9 (50%), and AJCC stage pT3 or greater in 14 (77.8%).

Conclusion

Among 31 examined BM dMMR CRAs, cases that demonstrated Mcl-1 expression were associated with a lower grade, lower rate of lymphovascular invasion and lymph node metastasis, and lower AJCC stage. While Mcl-1 expression confers resistance to apoptosis, this study suggests that Mcl-1–positive tumors demonstrate pathologic features associated with a favorable clinical outcome.