bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMARCA4 Deficient Thoracic Sarcoma Presenting with a Pathologic Fracture of Proximal Tibia and L5 Vertebral Body: a Case Report and Review of Literature
Authors: Elzamly S , Murzabdillaeva A , Taha H , Shitawi M , Zhu H 
Published: October 2020

Abstract

Introduction/Objective
SMARCA4 (BRG1) is a central component of the Switch/Sucrose-Non-Fermentable (SWI/SNF) chromatin remodeling complex which plays a critical role in the initiation, progression and dedifferentiation of a variety of cancers arising in different anatomical sites. The recently discovered SMARCA4-deficient thoracic sarcoma (DTS) can present as a mediastinal, pleural or pulmonary mass and constitutes a unique and highly lethal entity.

Methods
Here we present an interesting case of a 66-year-old, smoker male with past medical history of COPD, polysubstance abuse, hepatitis C virus, and alcoholic cirrhosis who presented with left proximal tibia pathological fracture, L5 vertebral body lytic lesion, left leg cellulitis and hypercalcemia. Imaging studies, tibia biopsy, thoracocentesis, histopathological examination, and immunohistochemical stains were performed.

Results
Imaging studies revealed a 3.1 cm, right upper lobe speculated lung mass along with multiple other lung nodules. Numerous arterially enhancing hepatic masses up to 2.8 cm were also identified. The patient underwent intramedullary nail, cementation and tibia biopsy followed by thoracentesis a month later.The histological sections revealed sheets of poorly differentiated malignant epithelioid cells showing high nuclear pleomorphism, prominent nucleoli, eosinophilc cytoplasm with extensive necrosis, and high mitosis (Ki-67 around 100%). The tumor cells lacked the expression of SMARCA4 (BRG1), cytokeratin, SALL4, CD34, TTF-1, P40, S100, HMB45, pan melanoma, desmin, CD31, ERG, CD30, CD56, chromogranin, CD38, CD45, CD3, ALK-1, myeloperoxidase, glypican-3, hepatocyte, and inhibin with mixed kappa and lambda. Tumor cells expressed SATB2 and focal synaptophysin, consistent with SMARCA4 deficient thoracic sarcoma metastasizing to the bone. The patient’s condition rapidly deteriorated and he died within two months.

Conclusion
An accurate diagnosis of these tumors is paramount and can be challenging. However, recognizing SMARCA4-DTS from other types of epithelioid tumors that involve the thoracic region is clinically relevant, as targeted therapies for SMARC-deficient tumors are currently being investigated and new clinical trial data show therapeutic benefit.
A Diagnostically Challinging Case of Primary Thyroid Kappa-restricted Plasma Cell- Rich Hematolymphoid Neoplasm with Focal Plasmablastic Differentiation
Authors: Haleema S O , Akbar S , Rowley E , Polski J M , Mneimneh W 
Published: October 2020

Abstract

Introduction/Objective
Most low-grade B-cell lymphomas of the thyroid are extranodal marginal cell lymphomas (MZL) and may exhibit focal plasma cell differentiation (PCD). PCD could occasionally be extensive, mimicking a true plasma cell neoplasm (PCN). PCN of the thyroid are extremely rare, representing either a component of plasma cell myeloma (PCM), or a primary thyroid extraosseous plasmacytoma (EOPC). We present a case of primary thyroid plasma cell (PC)-rich neoplasm with considerable diagnostic challenge.

Methods
A 46-year-old male underwent total thyroidectomy for hypothyroidism and compressive symptoms. Microscopically, sheets and nodules of PC with focal plasmablastic features were demonstrated in a background of fibrosing chronic thyroiditis. One benign perithyroidal lymph node was seen. The differential diagnosis included B-cell neoplasm with extensive PCD (ie, MZL or lymphoplasmacytic lymphoma) and PCN.

Results
Immunohistochemically, the PCs were positive for CD79a, MUM1, BCL2 and IgM with Kappa light-chain restriction and partial CD138 expression, and negative for CD20, PAX5, HHV8, Cyclin-D1, SOX11, CD117 and IgG. EBER was negative. Rare reactive-appearing B-cell aggregates with associated T-cells were noted. FISH for API/MALT1-fusion t(11;18) and PCR for MYD-88 mutation were negative. However, polysomy 18 (seen in 15–33% of B-cell lymphomas, including MZL) was detected. Serum proteins and PCM workup were negative.
The findings were consistent with primary thyroid Kappa-restricted PC-rich neoplasm. While the absence of detectable B-cell neoplastic component was suggestive of EOPC, the diagnosis of MZL with extensive PCD was favored due to the thyroid involvement in a background of thyroiditis, absence of lymph node involvement, detection of polysomy 18, and absence of MYD-88. Follow-up of the patient was thought to be most reasonable.

Conclusion
Plasma cell-rich hematolymphoid neoplasms of the thyroid may cause a considerable diagnostic challenge. Differentiating between B-cell lymphomas with extensive PCD and PCN may be difficult or even impossible by morphology alone. Additional ancillary tests may be necessary.
Case Report: Coexistence of Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix
Authors: Tran T T , Bhuyan R , Peng S 
Published: October 2020

Abstract

Introduction/Objective
Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are very rare tumors, accounting for less than 1% of all cervical adenocarcinomas. ACC is an aggressive neoplasm and has poor prognosis while ABC has a favorable prognosis. Coexistence of ACC or ABC and squamous intraepithelial lesion/invasive squamous cell carcinoma in the uterine cervix has been reported in the literature; however, coexistence of ACC and ABC in the uterine cervix is very rare.

Methods
Case presentation: Here we present a case of coexistence ACC and ABC in a 66-year-old woman who suffered from heavy bloody vaginal discharge for one year with weight fluctuations. The cervical exam and CT scan showed a friable mass at the uterine cervix, measuring up to 5.5 cm, and cervical mass punch biopsy was performed. Histopathological examination of the specimen revealed an intact nonkeratinizing stratified squamous epithelium overlying proliferation of nests punctuated by small round spaces, resembling cribriform pattern in the stroma. The tumor cells were small and basaloid with hyperchromatic nuclei and scant cytoplasm. Palisading of tumor cells at the peripheral of the tumor nests were observed in some areas. Mitotic figures and necrosis were not seen.
Immunohistochemical stains were performed and showed two distinct patterns of ACC and ABC. ACC tumor cells were positive for CD117, focally positive for CAM5.2 and S100, and negative for p63. ABC tumor cells were positive for p63 and EMA and negative for CD117 and S100. Both ACC and ABC components were positive for p16, Sox 10, BCL-2 and vimentin and negative for CK7, p40, CEA and ER. PAS stain showed positive staining in the basement membrane-like material in ACC component. A final pathologic diagnosis of coexistence of ACC and ABC of the uterine cervix were made.

Conclusion
Literature review revealed that this was an exceedingly rare case of coexistence of ACC and ABC in the uterine cervix. It is extremely important to correctly diagnose ACC and ABC as there is very poor prognosis in the former and good prognosis in the latter.
Urinary Bladder Transitional Cell Carcinoma with Chordoid Features-A Rare Entity
Authors: Kozman D , Heneidi S , Ullah A , Ghleilib I , Vemavarapu L , Dykes T 
Published: October 2020

Abstract
Casestudy: Invasive urothelial carcinoma is heterogenous entity and show variant morphologic patterns, of which squamous differentiation is the most common. Other variants have been widely recognized and studied.
Invasive urothelial carcinoma with chordoid features is a rare entity with only 16 reported cases to date in English literature. It has a significant morphologic overlap with other vesical and non-vesical myxoid neoplasms, including extra-skeletal myxoid chondrosarcoma and chordoma, which necessitate an extensive workup to reach an accurate diagnosis.
To the best of our knowledge we report the 17th case of urothelial carcinoma with chordoid features in a 76-year-old male who underwent a cystoprostatectomy and bilateral pelvic lymph node dissection with confirmed diagnosis of high-grade invasive urothelial carcinoma on biopsy. Grossly, bladder showed a 4.2 x 3.4 x 0.6 cm firm white tumor entirely replacing the anterior wall, extending into perivesicular fat, and invading the prostate gland and seminal vesicles.
Microscopically, tumor showed urothelial carcinoma in-situ transitioning into high-grade invasive carcinoma with chordoid features. The tumor characterized by round to elongated epithelial cells and eosinophilic cytoplasm arranged in a single file/complex cord-like architecture, in a prominent myxoid stromal background. No conventional high-grade spindle cell morphology was identified. Pelvic lymph nodes were positive for metastatic disease. Tumor cells were positive for GATA3, Pan-cytokeratin, 34BetaE12, and p63, while negative for AMCAR, supporting the urothelial origin of this tumor and confirming the diagnosis.
Invasive urothelial carcinoma with chordoid features is a rare entity, generally present at high stage disease, that can be mistaken for other prominent myxoid stromal neoplasms and requires careful assessment. Although, it can demonstrate similar demographic, clinical and immunohistochemical staining pattern as of conventional urothelial carcinoma, special attention should be given to exclude sarcomatoid features which is an aggressive variant of urothelial carcinoma.
Granular Cell Tumor Confined To The Muscularis Propria Of The Appendix: A Case Report
Authors: Allison D , Rao D 
Published: October 2020

Abstract

Introduction/Objective
Granular cell tumors (GCTs) are exceedingly rare soft tissue tumors that are usually benign and are thought to arise from Schwann cell origin. GCTs most commonly occur in the skin, subcutaneous tissue, and oral cavity. However, they can involve any organ, including the gastrointestinal (GI) tract, of which esophagus is most common, followed by large intestine. We report a case of a 58 year old female who presented with acute
appendicitis, followed by an appendectomy to reveal an incidental GCT.

Methods
This report is a retrospective study of an appendiceal GCT in which we reviewed the case and the histology. In addition, a brief literature review of gastrointestinal GCTs was performed to further elucidate the incidence, location, histopathology, and differential diagnoses for this lesion.

Results
Histological analysis of the tumor nodule reveals nests of epithelioid cells with abundant granular eosinophilic cytoplasm. The nuclei are bland, small, and round to oval, with rare spindled morphology.
Immunohistochemistry for S-100 protein shows diffuse strong cytoplasmic and nuclear positivity, which is suggestive of Schwann cell origin. In the GI tract, GCTs are routinely confined to the mucosa, submucosa, or both; however the tumor nodule in our case is contained within the muscularis propria.

Conclusion
It is estimated that 5–11% of GCTs occur in the gastrointestinal tract, while only 13 GCT cases of the appendix have been reported. In addition to the previously stated rarity, is the limited involvement of the muscularis propria, with which GCTs typically are not associated. To our knowledge, this is the first confirmed GCT of the appendix that solely involves the muscularis propria, in English medical literature.
PD-L1 Expression in Anal Intraepithelial Neoplasia Versus. Invasive Squamous Cell Carcinoma
Authors: Monsrud A , Avadhani V , Mosunjac M , Krishnamurti U 
Published: October 2020

Abstract

Introduction/Objective
Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal lesions. In this study we compare PD-L1 expression in anal squamous intraepithelial lesions (SIL/AIN) with that in invasive squamous cell carcinoma (ISCC)

Methods
After IRB approval, formalin-fixed paraffin embedded sections from 84 patients (51 with ISCC and 32 without ISCC), from 2010–2018, were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). These included 15 cases with normal mucosa, 60 cases with low grade squamous intraepithelial lesion (LSIL/AIN 1), 52 cases with high grade intraepithelial lesion (HSIL/AIN2-3), and 51 cases of ISCC. Overall tumor proportion score of &gt; 1% tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +).

Results
PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases of ISCC. Staining was heterogenous in all PD-L1 positive cases, with invasive foci that were negative to 100% positive. Tumor proportion score ranged from 1% to 50%. No PD-L1 membrane positivity was seen in any of the normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3. Even in cases of microinvasive or invasive carcinoma, PD-L1 positivity was seen only in the invading malignant cells and not in the overlying or adjacent HSIL. One case showed aberrant nuclear staining in 10% of cells in LSIL and HSIL. About 25% of cases showed non-specific basal granular cytoplasmic staining in normal mucosa, LSIL, and HSIL, that correlated with the presence of melanin. Cases with normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3, were equally distributed between cases with no invasive carcinoma, PD-L1 positive ISCC, and PD-L1 negative ISCC.

Conclusion
No PD-L1 positivity (membrane staining) was present in normal mucosa or anal squamous intraepithelial lesion/anal intraepithelial neoplasia in our study. Any nuclear staining or granular cytoplasmic staining should not be interpreted as PD-L1 positivity. PD-L1 was only positive in a subset (35%) of invasive squamous cell carcinoma. The expression of PD-L1 is likely to be associated with an invasive malignant process and is a potential target for therapy with PD-L1 inhibitors.
A Case Report Of A Spindle Cell Sarcoma With Ntrk-3 Rearrangement And A Novel Gene Fusion Partner (Ntrk3-Eif2s2)
Authors: Shalaby A , Alhussain A , Al Hmada Y , Bernieh A 
Published: October 2020

Abstract

Casestudy
A group of spindle cell tumors with characteristic morphologic features, co-expression of CD34 and S100 and recurrent gene rearrangements in RAF-1, BRAF, and NTRK has recently been described. These tumors were found to be previously labeled as malignant peripheral nerve sheath tumor, infantile fibrosarcoma or unclassified spindle cell sarcoma. We describe a case of a 25-year-old female who presented with a right thigh mass. She underwent an ultrasound-guided biopsy showing a spindle cell tumor with co-expression of CD34 and S100 and subsequently underwent resection of the mass. Gross examination showed a 7.5 cm multi-lobulated, tan-pink, hemorrhagic and fleshy mass. Histologically, the tumor was relatively well-demarcated and consisted of spindle cells with moderate to high cellularity in a patternless architecture. The spindle cells showed moderate to marked pleomorphism, pale amphophilic cytoplasm, ovoid-to-elongated nuclei with vesicular chromatin, and occasional prominent nucleoli. Areas of prominent perivascular and stromal hyalinization were seen. Mitotic activity was brisk with up to 33 mitoses per 10 high power fields. Necrosis representing approximately 5% of the mass was identified. On immunohistochemistry, the tumor cells showed strong and diffuse positivity for CD34 and S100 and were negative for SOX10, broad-spectrum cytokeratin, EMA, SMA, Desmin, STAT6, MUC4, TLE1, and H3K27me3 (retained nuclear expression). EIF2S2-NTRK3 fusion gene was detected using next generation sequencing analysis.

Conclusion
A few cases of NTRK3 spindle cell sarcomas, other than classic infantile fibrosarcoma, have been previously reported in the literature with fusion genes involving ETV6, EML4, and STRN, among others. A gene fusion involving NTRK3 and EIF2S2 has not been previously reported. NTRK3-fused sarcomas typically show high-grade morphology and aggressive clinical behavior. Identification of NTRK-fused sarcomas is clinically important, as these advanced tumors are potentially amenable to NTRK inhibition. In our case, patient received adjuvant post-operative radiation therapy and returned with lung metastasis 5 months after surgery.
A Rare Presentation of Pseudomembranous Colitis in a COVID-19 patient
Authors: Jabbar A , Rana T , Ilyas G , Baqir A , Emechebe D , Agaronov M 
Published: October 2020

Abstract

Introduction/Objective
Recent reports suggest that though COVID-19 is predominantly a respiratory pathogen, one of its presenting features can be gastrointestinal symptoms. We hereby present a case of a female with COVID-19 infection whose hospital course was complicated by colonic pseudo-obstruction caused by pseudomembranous colitis resulting in an emergent hemicolectomy.

Methods
A 59-Year-old female with history of hypertension, diabetes, and breast cancer post mastectomy presented with pneumonia and was confirmed to be COVID-19 positive. She was admitted to the hospital and was treated with Azithromycin for 6 days. Patient developed constipation on day six of hospitalization and started having abdominal pain on day eight with elevated WBC count. Imaging showed distension of cecum and proximal colon. She underwent exploratory laparotomy which revealed a necrotic appearing cecum that was massively dilated and had a serosal tear. These findings prompted emergent hemicolectomy with loop ileostomy. Grossly cecum was black/green, dilated, thin walled with a 5 x 5 cm yellow green raised plaques. Microscopy of the plaques revealed focal erosion of colonic mucosa with overlying acute inflammatory cells, fibrin deposits, mucus, and necrotic epithelial cells consistent with pseudomembranous colitis.

Conclusion
Review of literature shows no reported cases of intestinal pseudo-obstruction due to pseudomembranous colitis in a COVID-19 patient. Not only this, but there are also only a limited number of case studies of pseudomembranous colitis presenting as intestinal pseudo-obstruction without diarrhea. Though this patient’s presentation could be from Clostridium difficile infection secondary to Azithromycin, it is not a common antibiotic to cause this. Also, one of the known causes of pseudomembranous colitis is ischemia. Given that COVID-19 infection is a pro-thrombotic condition, possible ischemia secondary to COVID-19 infection related coagulopathy should also be a consideration.
Hirschsprung’s Disease: Two Cases of Total Intestinal Aganglionosis
Authors: Ramachandran V , Nguyen J , Caruso C , Rao D 
Published: October 2020

Abstract

Introduction/Objective
Hirschsprung’s disease is a disorder associated with an absence of ganglion cells in a segment of the bowel. Total colonic and small bowel aganglionosis occurs in less than 1% of all Hirschsprung’s disease patients. Even rarer is the finding of Haddad syndrome, the coexistence of congenital central hypoventilation syndrome and Hirschsprung’s disease. Congenital central hypoventilation syndrome has approximately 1,000 reported cases, with colonic aganglionosis being associated with 15-20% of those cases. The prevalence of Hirschsprung’s disease with congenital renal anomalies may be another underreported finding.

Methods
Here, we report two rare cases of Hirschsprung’s disease with significant extension in the small bowel. One case involves a 38-week gestational age male infant admitted for apnea and another case involves 39-week gestational age female infant admitted for vomiting.

Results
Both infants had rectal suction biopsies confirming the absence of ganglion cells. The male infant had mapping biopsies which histologically showed hypertrophic nerve fibers and an absence of ganglion cells in the colon extending up to 70 cm proximal to the ileocecal valve. Calretinin immunostaining confirmed aganglionsis. Genetic testing showed a PHOX2B gene mutation carrying 32 polyalanine repeat mutations, confirming a diagnosis of congenital central hypoventilation syndrome coexisting with Hirschsprung’s disease. The female infant had intraoperative frozen sections that identified ganglion cells throughout the colon. On permanent sections, there was an absence of ganglion cells in the upper rectum extending up to 65 cm proximal to the ileocecal valve. She also was noted to have agenesis of the left kidney and a urachal remnant. Genetic testing was negative for RET mutations.

Conclusion
Overall, these cases provide further information on a rare variant of Hirschsprung’s disease that includes significant portions of the small bowel. Additionally, this study adds to the documented reports of Haddad syndrome and the connections between renal anomalies with Hirschsprung’s disease. Last, this series alludes to the difficulties of frozen section diagnosis of this disease.
Russell Body Duodenitis In A Patient With Duodenal Adenoma And High-Grade Dysplasia
Authors: Sun L , Allison D , Yin F 
Published: October 2020

Abstract

Introduction/Objective
Russell bodies are nondegradable, condensed immunoglobulins accumulated in the overstimulated plasma cells, and the plasma cells filled with Russell bodies are called Mott cells. Russell body gastroenteritis is a rare entity that is mainly occurs in stomach and is associated with Helicobacter pylori infection.
However, Russell body duodenitis is very rarely seen, so far only about four cases have been reported. Here we report a case of Russell body duodenitis within concurrent large duodenal adenoma with high-grade dysplasia in a 66- year old female.

Methods
Formalin fixed, paraffin embedded tissue was examined stained with H&E and PAS-Alcian blue stain. Immunohistochemical stains (IHC) with appropriate controls were performed with the following antibodies: H. pylori, CD138, kappa and lambda light chains.

Results
A 66-year old female had symptoms of difficult swallowing and decreased food intake. Upper GI endoscopy was performed to reveal a 7 cm multilobulated mass at the junction of the duodenal bulb and second portion of the duodenum, which involved the ampullary orifice. A biopsy for the mass showed a duodenal adenoma with high grade dysplasia. Numerous Mott cells were diffusely distributed within the lamina propria that was characterized by bright eosinophilic cytoplasmic globules with eccentric nuclei. The Mott cells were confirmed by IHC stains with positive CD138, PAS-Alcian blue, and polytypic expression of kappa and lambda light chains. The Helicobacter pylori immunostain was negative.

Conclusion
Although the etiology is unknown, most of the Russell body gastroenteritis are seen in benign conditions. It is mainly found in stomach associated with Helicobacter pylori infection. To our knowledge, this is the first reported case of Russell body duodenitis with concurrent duodenal adenoma with high-grade dysplasia. Further studies should be conducted on Russell bodies associated with high-grade dysplasia or carcinoma in gastrointestinal tract.