bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomorphologic findings of SMARCA4-deficient thoracic sarcoma/carcinoma: Report of two cases
Authors: Abu-Salah A K , Segura S , Cramer H M 
Published: October 2021

Abstract

Introduction/Objective
SMARCA4-deficient thoracic sarcoma/carcinoma is a highly aggressive neoplasm characterized by SMARCA4 (chromatin remodeling complex) deficiency. It affects mostly smokers (85%) with a broad age range of presentation (mean age: 50 years). Most patients present with advanced disease and extensive involvement of thoracic structures. The cytomorphologic features of this entity have not been fully described.

Methods/Case Report
A 59-year-old female, former smoker, with a prior history of lung adenocarcinoma, presented with a new 2.8 cm right infrahilar nodule concerning for recurrence. The second patient, a 54-year-old male who is a smoker, presented with an 8.0 cm right perihilar mass extending into the right lung and mediastinum with encasement of the right main pulmonary artery. Cytologically, the smears from both aspirates were comprised of single cells and loosely cohesive clusters of ovoid to spindle cells with scant to moderate cytoplasm, stippled chromatin, and focally prominent nucleoli. Numerous mitotic figures were appreciated. Necrosis was present within the smear background. The cell block sections showed tumor cells arranged in glandular and focal papillary architecture with a myxoid background. In one case, intermediate to large-sized cells with focal cytoplasmic clearing and patchy extracellular metachromatic material were also noted. Rhabdoid morphology was not appreciated. Immunohistochemically, the tumor cells were at least focally positive for vimentin, TLE-1, SALL4, CK AE1/AE3 and TTF-1, while being negative for CK7, CK20, Napsin-A, SOX-10, p40 and neuroendocrine markers. Both tumors showed SMARCA4 (BRG1) loss of expression.

Results (if a Case Study enter NA)
N/A

Conclusion
While the cytomorphologic findings of SMARCA4-deficient thoracic sarcomas/carcinomas are not specific, the FNA diagnosis should be considered for any poorly differentiated neoplasm involving the lungs or mediastinum which should prompt an appropriate immunocytochemical work-up that includes SMARCA4/BRG1 assessment
Effusion tumor cell (ETC) detection from cytology samples following long-term storage
Authors: Libert D , Allard G , Zhu Y , Lowe A C 
Published: October 2021

Abstract

Introduction/Objective
Circulating tumor cells (CTCs) are shed from solid tumors into blood. The RareCyte CTC system involves multiplexed fluorescence whole-slide imaging of blood for antibody-based identification of EpCAM/cytokeratin-positive and CD45-negative CTCs. We have previously established an assay to detect carcinoma effusion tumor cells (ETCs) from remnant pleural fluid samples employing RareCyte, providing a potential avenue for tumor cell detection from any cytology sample. To facilitate this, our aim is to evaluate slide storage conditions. We hypothesize that long-term storage of pleural fluid ThinPrep slides at -20°C prior to RareCyte analysis will yield similar ETC numbers and characteristics to freshly-prepared slides.

Methods/Case Report
ETCs were identified and counted via RareCyte according to our previously established criteria (EpCAM mean fluorescence intensity (MFI) &gt; 100 arbitrary unit (a.u.), CD45 MFI &lt; 100 a.u., and cellular morphology). We analyzed 7 paired fresh-stored pleural fluid samples. Stored samples were maintained at -20°C for 154 or 385 days. ETCs counts between the fresh and stored conditions were compared using a Wilcoxon signed-rank test. Marker intensities from the 35 EpCAM-brightest cells across one paired fresh-stored sample were compared using a two-tailed independent t-test. The cutoff for significance is p&lt;0.05.

Results (if a Case Study enter NA)
The median (25%, 75%) number of cells detected in the 7 fresh and stored samples was 36 (14, 129) and 13 (5, 22), respectively, and was not significantly different (p=0.08). Although the MFIs for DAPI nuclear staining (p=0.12) and CD45 (p=0.82) were not significantly different between the fresh and stored 35 EpCAM-brightest cells, cytokeratin (p=0.02) and EpCAM (p&lt;0.00001) MFIs were significantly less in stored samples.

Conclusion
Detecting ETCs is possible after long-term storage at -20°C despite a significant decrease in EpCAM and cytokeratin MFIs in stored samples. In this small sample, paired ETC counts were not significantly different. These preliminary results provide a foundation for larger studies to define storage conditions.
Pleural Metastasis of High-Grade Endometrial Stromal Sarcoma With YWHAE Gene (17p13.3) Rearrangement, A Rare Case Report
Authors: Re A C , Enrique M , Ren S 
Published: October 2021

Abstract

Introduction/Objective
Endometrial stromal sarcoma (ESS), a rare malignant neoplasm of endometrial stroma, accounts for less than 1% of all uterine tumors. High grade ESS (HGESS) is aggressive and commonly relapses even after surgical and neoadjuvant therapy. Abdominal and pelvic regions are common sites of metastasis, however, distant metastases to the liver, lung, vertebrae, and brain have been reported.

Methods/Case Report
We encountered a 49-year-old female who presented with shortness of breath, found to have a left pleural effusion and multiple pleural masses. She initially presented three years ago with heavy irregular menses and left pelvic pain for one year. D&C revealed prominent small spindle cells for which a stromal nodule and low-grade or malignant process was probable. CT scan showed an enlarged uterus. Hysterectomy with bilateral salpingo- oophorectomy, bilateral pelvic and para-aortic lymph node dissection, and partial omentectomy were performed. The uterus revealed an intramural 7 cm mass with a serpiginous growth pattern and lymphovascular invasion. Tumor cells were plump to spindled with areas of high cellularity, rounded nuclei, increased atypia and mitosis. Atypical areas were positive for cyclin D1, focally positive for CD10, and negative for ER, PR, SMA, desmin, AE1/3 and CAM5.2. FISH studies showed rearrangement of YWHAE gene (17p13.3) and no rearrangement of JAZF1 or PHF1 gene regions. Findings supported the diagnosis of HGESS. The patient received post-operative chemotherapy. Biopsy of the current pleural lesion revealed a nonspecific malignant spindle cell neoplasm positive for BCL1, CD56, CD117, CD99, TLE1 and INI1, while negative for AE1/3, CAM5.2, EMA, ER, PR, CK5/6, calretinin, SMA, desmin and S100. The CD10 stain was inconclusive. FISH studies showed rearrangement of YWHAE gene (17p13.3) and no rearrangement involving JAZF1 or PHF1 gene regions. No rearrangement of the SS18 gene region was observed and synovial sarcoma was excluded. Overall findings support the diagnosis of metastatic HGESS.

Results (if a Case Study enter NA)
NA

Conclusion
HGESS, a rare tumor with a nonspecific immunostain profile, has the ability to metastasize to rare body sites, such as the pleura in our case. Display of spindle cell morphology is a nonspecific finding that raises broad differential diagnoses. In women, with or without a history of uterine neoplasm, HGESS is a clinically worthwhile diagnosis to be mindful of.
Choriocarcinoma Presenting as a Metastatic Pancreatic Mass: a Cytopathologic Diagnostic Challenge
Authors: Al-Attar M M , Zou T , Fischer A H , Cosar E F 
Published: October 2021

Abstract

Introduction/Objective
Choriocarcinoma is a malignant tumor of trophoblasts, with gestational choriocarcinoma as the most common type. It commonly presents with vaginal bleeding and uterine mass; occasionally, hemorrhage due to metastatic disease to the lung, liver, brain, and gastrointestinal tract may be the first presentation. We describe an unusual case of metastatic gestational choriocarcinoma presenting as a pancreatic head mass mimicking a pancreatic neuroendocrine tumor (PanNET). The concern for choriocarcinoma was raised by fine-needle aspiration (FNA) cytology.

Methods/Case Report
A 32-year-old woman, 16 months status-post caesarian delivery of healthy twins, presented with progressive right upper quadrant and epigastric pain, nausea, and marked elevation of Beta-hCG, lipase, ALT, and AST levels. Abdominal CT revealed a hypoenhancing 2.6 cm pancreatic head mass and multiple liver nodules, suggestive of PanNET with liver metastasis. Endoscopic ultrasound and FNA of the pancreatic mass revealed a poorly differentiated tumor composed of bizarre large malignant cells with marked cytologic atypia, focal spindle cell change, and rare multinucleated cells. By immunohistochemistry, the tumor cells were positive for pancytokeratin, CAM5.2, and CD56 (focally), while negative for synaptophysin, chromogranin, inhibin, P63 and P40. While pancreatic adenocarcinoma and PanNET couldn’t be completely ruled out, metastatic choriocarcinoma was also considered; however, inconclusive immunostaining warranted a tissue biopsy. Follow-up liver biopsy and FNA showed that tumor cells were positive for Beta-hCG and negative for SALL4, placenta lactogen, HepPar1, and TTF1 immunostains, compatible with choriocarcinoma. Molecular analysis using short tandem repeat supported a gestational origin of the tumor. The patient underwent chemotherapy with marked improvement in her status and beta-hCG levels.

Results (if a Case Study enter NA)
NA

Conclusion
Although highly aggressive, gestational choriocarcinomas show good treatment response, necessitating accurate diagnosis in cases of an atypical presentation. Choriocarcinoma presenting as metastatic pancreatic mass is extremely rare and poses a diagnostic cytopathologic and radiologic challenge that requires comprehensive correlation with clinical and laboratory data.
Laboratory Management for Cytopathology Fellows: Our Institution’s Curriculum
Authors: Mir F , Reynolds J , Chute D , Dyhdalo K 
Published: October 2021

Abstract

Introduction/Objective
The cytopathology laboratory is one of the most highly regulated clinical laboratories. The Accreditation Council for Graduate Medical Education (ACGME) milestones include competencies in laboratory management. Additionally, many cytology fellows will be involved in laboratory management after finishing training. Therefore, it is imperative to incorporate formal laboratory management training for cytology fellows. Our cytopathology department implemented a formal laboratory management curriculum this year, with emphasis placed on the milestones (1.0 and 2.0) provided by the ACGME.

Methods/Case Report
The curriculum is divided into seven modules extending throughout the fellowship year (August-April). The modules include hand-off communication, process improvement, laboratory accreditation (introduction, intermediate, advanced) and error management (introduction, intermediate). Each module has two components: self-study of assigned reading materials and online courses, followed by an interactive session with faculty and/or laboratory personnel. Several engaging, high-quality resources are used including Institute for Healthcare Improvement Open School, modules from professional organizations, PubMed articles, National Quality Forum, departmental committees and mock inspections. Each module is followed by an interactive session to review policies, procedures and/or checklists. The fellows also spend time in the cytology laboratory preparation area and participate in Quality Improvement meetings.

Results (if a Case Study enter NA)
The fellowship director discusses the educational expectations at the start of each module. Evidence of compliance is demonstrated by uploading all of the completed assignments to MedHub (a web- based training management system) at the end of the module. All of the modules include self-assessment questions that are reviewed by the fellowship director.

Conclusion
Our cytopathology laboratory introduced a structured laboratory management curriculum. This curriculum fulfills some of the laboratory management competencies put forth in the ACGME milestones. This curriculum will also help to prepare fellows to confidently participate in cytology laboratory management as they enter the workforce.
Cutaneous metastatic osteosarcoma – A rare case report
Authors: Sallagonda A , Henneberry J 
Published: October 2021

Abstract

Introduction/Objective
Osteosarcoma is an aggressive malignant primary bone tumor with common metastases to lungs via hematogenous spread. Other common sites of metastasis include bone and kidneys. Metastasis (excluding extraskeletal) to the skin is extremely rare. To date, roughly 12 cases of cutaneous metastasis have been reported in the literature.

Methods/Case Report
We report a 44-year-old female patient with a history of osteosarcoma of proximal tibia who underwent wide local excision in 2018 and subsequent chemotherapy. Approximately 2 years after her initial diagnosis, she presented with a painful mass in the left mid-thigh. Imaging studies revealed a 1.7 cm calcified nodule suspicious for metastatic osteosarcoma or a partially calcified granuloma. Fat necrosis and old hematoma were also considered in the radiographic differential, although less likely. An excisional biopsy was performed, which showed a high grade osteoid-producing tumor involving the deep dermis and subcutaneous adipose tissue confirming a metastasis of osteosarcoma. A new skin nodule developed at the same site six months later; though radiographic imaging studies were suggestive of subcutaneous fat stranding in the setting of cellulitis or vascular insufficiency. Given her prior history, another excisional biopsy was performed, which showed recurrent metastatic osteosarcoma.

Results (if a Case Study enter NA)
NA

Conclusion
Metastatic osteosarcoma to the skin is a rarely reported event in the literature. The prior clinical history and high index of clinical suspicion are essential in rendering the correct diagnosis. As the skin may be the first site of metastases it is important to include metastatic osteosarcoma in the differential in patients with a prior history of osteosarcoma who develops new skin or subcutaneous lesions. This case highlights the importance of providing history to the pathologist, as other tumors and non-neoplastic lesions can mimic osteosarcoma, particularly in small biopsy specimens. The easier access to the skin/ subcutis could also aid in obtaining tissue for molecular testing.
Giant Squamous Cell Carcinoma on The Scalp of A Young African American Male
Authors: Ding L , Yang B , Soofi Y , Slawinski G 
Published: October 2021

Abstract

Introduction/Objective
Skin cancer comprises 1-2% of all cancers in African American (AA) patients. Among all skin cancers, squamous cell carcinoma (SCC) is the most common one in AA, with an incidence of approximately 3 per 100,000. It mainly affects patients over 50-year-old. The most common locations of SCC (60-70% of cases) in AA were the sun-protected areas such as the lower limbs and anogenital region, rather than sun-exposed areas.

Methods/Case Report
We report a case of a 40-year-old AA male with longstanding folliculitis decalvans presenting with giant SCC. In 2016, the patient noted the enlargement of the atrophic hyperpigmented plaques on the right posterior scalp. They grew into a 10.5 x 10 x 4.5 cm exophytic, verrucous-like mass when the patient presented to the clinic in 2021. A skin biopsy of the giant mass showed pseudoepitheliomatous hyperplasia with cytologic atypia. CT scan ruled out underlying bone invasion. After that, the mass was resected with minimal 3-cm negative margins. Histological evaluation reveals a moderately differentiated keratinizing SCC with clear cell changes in a background of severe acute and chronic inflammation, folliculitis, and scar. No lymphovascular invasion is noted. An over 10-cm SCC arising within folliculitis decalvans on the scalp of a young AA patient is rare. To our knowledge, this the first report of such a case. Despite the limited data available, chronic scarring process and inflammation, instead of sun damage, are believed to be the most important risk factors for SCC development in the AA population. SCC greater than 4cm in chronic inflammation/scar is strongly associated with a poor prognosis. Therefore, early diagnosis, treatment, and close follow-up are critical.

Results (if a Case Study enter NA)
NA

Conclusion
Our report emphasizes (1) biopsy has limitations in diagnosing giant cutaneous neoplasms due to inadequate sampling; (2) the need for growing awareness, earlier diagnosis, and skin cancer treatment in people of color.
Immunohistochemical diagnosis of onychomycosis by monoclonal antibodies detection of dermatophyte T. rubrum
Authors: Audon P , Sigurdarson H , Guzman Y , Hua C , Bach M , Bach D , Villaluz S 
Published: October 2021

Abstract

Introduction/Objective
Onychomycosis is one of the most common nail infection disorders, caused predominantly by T. rubrum. Currently, PAS stain is the gold standard for histological onychomycosis detection. However, it does not differentiate between the types of fungi. In addition, PAS stains will only provide a positive or negative result. This leaves physicians to prescribe medications that may be ineffective in treating the root cause of the infection. By discerning the causative specie, physicians can provide a more targeted and effective anti-fungal therapy. A novel monoclonal antibody can be utilized to improve histological findings of T. rubrum. Our study takes a step forward to bring the monoclonal antibody into histological application. We have developed a new monoclonal antibody stain which binds to T. rubrum in vitro. For our project, we will perform in vivo staining on clinical nail samples using the novel monoclonal antibody. Developing a new applicable technique will benefit patients with onychomycosis as well as promote research in targeted identification of other infectious pathologies.

Methods/Case Report
Data from Bach Dx’s collaboration demonstrate isolation and validation of mice monoclonal antibody candidates for T. rubrum. Isotype IgG1/kappa 17B6 had the highest binding pair signal to the analyte. Direct ELISA of 17B6.1E3 shows immunoreactivity to T. rubrum. HRP and AP conjugates to 17B6 mice monoclonal antibody are produced (Rockland Immunochemicals Inc. Gilbertsville, PA). Histology slides analyzed for routine onychomycosis analysis at Bach Diagnostics are subject to secondary analysis. 220 retrospective, unstained nail slides from 55 patients will be stained using the 17B6 stains. 40 patients were known to have tested for onychomycosis caused by T. rubrum, 5 by Candida albicans, 5 by T. interdigitale, and 5 tested negative. All samples were confirmed by histology and molecular tests. H&E, PAS, and naked antibody stains will serve as controls. HRP and AP conjugated 17B6 monoclonal antibody stains will be optimized to Quantum Hdx (StatLab Lodi, CA) on July 12th, 2021 when the stains are scheduled to arrive. Images will be captured by light microscopy, and analyzed quantitatively and qualitatively.

Results (if a Case Study enter NA)
We hope to show preferential staining of antibody stains to positive T. rubrum cases by end of July 2021.

Conclusion
Conclusion pending based on results.
Primary Cutaneous Cryptococcosis of Nasal Ala with Extensive Tissue Destruction
Authors: Nishiyama-Fujita Y , Xu Y , Kondapi D S , Parkerson G R 
Published: October 2021

Abstract

Introduction/Objective
Primary cutaneous cryptococcosis (PCC) is rare and shows skin lesion(s) confined to a circumscribed body region mostly in immunocompromised host, with no sign of simultaneous dissemination condition. PCC usually presents as non-specific skin lesions such as cellulitis, nodules, and ulcers, and can be misdiagnosed in biopsy. We present a case of PCC with extensive tissue destruction.

Methods/Case Report
A 43-year-old male, with a history of human immunodeficiency virus infection 17 years ago, presented with complaint of his nose slowly “being eaten away” over the past 5 years after a bike accident. Physical examination showed most of the left nasal ala was completely destroyed, with visualizable septum. The biopsy of the left nasal ala showed the dermis has numerous yeasts with marked variation in size and shape, in foamy stroma with little inflammation. The capsules of the yeasts were highlighted by Mucicarmine stain. Grocott methenamine silver stain showed budding yeasts. The diagnosis of cutaneous cryptococcosis, gelatinous type, was rendered. Primary cutaneous cryptococcosis was considered based on no disseminated disease found, positive serum cryptococcus antigen with low titer (1:20), the culture of the nasal lesion positive for Crptococcus Neoformans, and the history of skin injury. The patient received appropriate treatment for PCC subsequently.

Results (if a Case Study enter NA)
NA

Conclusion
We have demonstrated a very rare case of undiagnosed/untreated PCC causing extensive destruction of skin and underlying nasal tissue. Identification of the histological features of cutaneous cryptococcosis, shown in this case, is the key for making the correct diagnosis.
NTRK3-rearranged thyroid carcinoma, clinical and pathologic features
Authors: Skibiel C , Ren S , Reid L 
Published: October 2021

Abstract

Introduction/Objective
NTRK3 gene encodes a transmembrane protein receptor of the tropomyosin receptor kinase (Trk) family. Gene fusions involving NTRK3 result in a constitutive activation or overexpression of Trk receptor, potentially leading to oncogenesis. NTRK targeted therapies show a promising activity in varied cancer types with NTRK fusions. The aim of this case review is to describe the clinical and pathologic findings of thyroid neoplasm with NTRK3 gene fusions.

Methods/Case Report
The cytology fine needle aspiration (FNA), molecular testing results and pathology of surgical resections are reviewed in 220 cases of total and hemithyroidectomy from January 2018 to May 2021.

Results (if a Case Study enter NA)
Three cases with NTRK3 gene fusions are identified by Thyroseq or Afirma GSC from FNA of thyroid nodules with later surgical intervention. No other mutations or gene fusions were identified. Each case had total thyroidectomy. Case 1 is a 41-year-old female with FNA diagnosis of suspicious for papillary thyroid carcinoma (PTC) and ETV6/NTRK3 fusion found by Afirma GSC. Pathology diagnosis is PTC classic type, two tumor nodules 1.1cm and 1.0cm, lymphovascular invasion not identified, three lymph nodes not involved by tumor and pathologic stage pT1b(m) pN0. Case 2 is a 49-year-old female with FNA diagnosis of atypia of undetermined significance and ETV6/NTRK3 fusion detected by Thyroseq. Pathology diagnosis is infiltrative PTC follicular variant, 2.0cm, angioinvasion present, no lymph nodes submitted and pathologic stage pT1b(m) pNX. Case 3 is a 28-year-old female with FNA diagnosis of suspicious for follicular derived neoplasm and NTRK3/RBPMS fusion is detected by Afirma GSC. Pathology diagnosis is infiltrative PTC follicular variant, 1.5cm, 9 of 11 lymph nodes positive for metastatic carcinoma and pathologic stage pT1b pN1b.

Conclusion
Thyroid neoplasm with NTRK3-rearrangement is rare. Cases 1 and 2 with common ETV6-NTRK3 fusion show PTC classic type and infiltrative PTC follicular variant with angioinvasion. Case 3 with less common NTRK3/RBPMS fusion shows infiltrative PTC follicular variant and significant lymph node involvement. Our limited cases of NTRK3-rearranged thyroid carcinoma demonstrate infiltrative growth, diverse phenotypes, one case with angioinvasion and no lymph nodes submitted and one case with multiple lymph node metastasis. This suggests aggressive behavior of thyroid cancer with NTRK3 gene fusion and patients may benefit from targeted NTRK therapy.