bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroidogenic acute regulatory (StAR) protein is a useful marker for sex-cord-stroma tumors and normal/neoplastic adrenocortical tissue
Authors: Lennartz M , Amirzada D , Blessin N C , Gorbokon N , Hube-Magg C , Sauter G , Simon R , Kluth M , Bernreuther C , Steurer S , Krech T 
Published: November 2023

Abstract

Introduction/Objective
Steroidogenic acute regulatory (StAR) protein is a mitochondrial transport protein with a critical regulatory role for steroid hormone production. As its expression is limited to few normal tissues, the immunohistochemical analysis of StAR was proposed to be diagnostically useful.

Methods/Case Report
To comprehensively evaluate the diagnostic utility of immunohistochemical StAR expression analysis, a tissue microarray containing 19,202 samples from 152 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). Melan-A “cross-reactive” data were available from a previous study for comparison.

Results (if a Case Study enter NA)
StAR immunostaining occurred in 198 (1.2%) of the 17,135 analyzable tumors. StAR expression was observed in 27 of 152 tumor categories, 9 of which included at least one strongly positive case. The highest rate of StAR positivity occurred in Leydig cell tumors of the testis and the ovary (100%), steroid cell tumors of the ovary (100%), adrenocortical carcinomas (93%) and adenomas (87%), Sertoli-Leydig cell tumors (67%) and granulosa cell tumors of the ovary (56%) as well as in seminomas (7%). As compared to Melan A, StAR was more often positive in adrenocortical neoplasms and in Leydig cell tumors while StAR (but not Melan-A) was negative in Sertoli cell tumors.

Conclusion
Our data provide a complete overview on the patterns of StAR immunostaining in human tumors and suggest a diagnostic utility of StAR immunohistochemistry for supporting a diagnosis of Leydig cell tumors or of normal or neoplastic adrenocortical tissue. In contrast to Melan A, StAR appears to be more sensitive for these tumors while StAR is always negative in malignant melanoma, a frequent source of adrenal metastasis.
PD-L1 Expression Spatial Heterogeneity in Colorectal Adenocarcinoma
Authors: Jaramillo C , Hwang J , Brady R , Clifton G 
Published: November 2023

Abstract

Introduction/Objective
PD-L1 expression on colon cancer cells is associated with a worse prognosis[CGTLUMB(1] and may be an important selection marker in colon cancer patients for developing or combination immunotherapies in the future. A patient is eligible for targeted therapy if they demonstrate PD-L1 expression on a representative section, with different positivity threshold percentages used in different indications. However, little is known about the spatial heterogeneity of PD-L1 expression within tumors or how sampling bias may impact patient care. Here we report the results of a single institution retrospective study of PD-L1 heterogeneity in colorectal cancer to test the hypothesis that PD-L1 staining is homogenous throughout the tumor microenvironment.

Methods/Case Report
Long-term tissue storage at a single tertiary care center was queried for all cases of resectable (stage I-IV) colonic adenocarcinoma between 1 Jan 2014 and 1 Oct 2020. Cases with at least 4 formalin- fixed paraffin embedded blocks with tumor were selected; exclusion criteria included neoadjuvant therapy and absence of residual tumor on resection. 8 patients were identified meeting inclusion criteria (mean age 68 17 years,
5:3 M:F). PD-L1 (5H1 monoclonal antibody) immunohistochemistry was performed on corresponding tissue. Percent tumor cells expressing PD-L1 in a representative 1mm2 area at invasive margin and central tumor was quantified for
each section on digital slide images acquired on an Aperio CS2 Digital Slide Scanner (Leica Biosystems, Wetzlar, Germany) using QuPath (Version: 0.4.3).

Results (if a Case Study enter NA)
The mean ± SD of PD-L1 staining was 2.7±4.4% at invasive margin and 0.2±0.25% within central tumor; no statistically significant difference between regions was identified (paired t-test, p=0.15). Notably, 2 of the 8 cases demonstrated ranges at the invasive margin (0-36% and 1.3-35%) that span the cutoff for several commercially available anti-PD-1/PD-L1 agents.

Conclusion
These findings demonstrate that PD-L1 quantification can vary significantly within the same tumor depending on where counts are performed. This has significant clinical implications as PD-L1 positivity and patient eligibility for targeted therapy is most often assessed in a single location. Our current clinical methods of assessing PD-L1 expression do not account for the spatial complexities of the tumor microenvironment and could contribute to inaccuracy of small volume biopsies.
Beta-Catenin Nuclear Expression in Squamoid Morules in Colorectal Adenomas: Clinicopathologic Study of Fifteen Cases
Authors: Centeno B , Ghayouri M , Jiang K , Lauwers G , Nakanishi Y , Perez D , Wu T , Bhalla R 
Published: November 2023

Abstract

Introduction/Objective
Squamoid morules are an intriguing finding rarely seen in colorectal adenomas, mimicking foci of microinvasion or neuroendocrine differentiation. Previous observations include mostly case reports and small series, with few examining the squamoid morules in detail.

Methods/Case Report
We identified fifteen colorectal adenomas with squamoid morules and collected clinicopathological data including age, sex, procedure, location, pathologic diagnosis, and size. A representative block was chosen for immunohistochemistry in each case. The expression of p40, p63, CK5/6, beta-catenin, synaptophysin, chromogranin, and Ki-67 in squamoid morules were examined immunohistochemically.

Results (if a Case Study enter NA)
The fifteen patients comprised thirteen males and two females ranging in age from 45 to 85 years (average: 60.6 years old). The adenomas were removed by endoscopic resection (n = 7) or surgical resection (n = 8). Nine adenomas were found in the rectosigmoid colon, one in the descending colon, and five in the right colon. Eleven adenomas were tubulovillous adenomas (average: 3.8 cm, ranging 1.0 to 6.0 cm) and four were tubular adenomas (average: 2.6 cm, ranging 1.6 to 3.0 cm). Seven adenomas contained invasive adenocarcinoma. Squamoid morules were randomly distributed in adenomas. All foci of squamoid morules showed beta-catenin nuclear positivity and most (more than 90 %) showed CK5/6 expression. Squamoid morules were focally positive for p63 in three adenomas and focally positive for p40 in one adenoma. In one adenoma squamoid morules are positive for both synaptophysin and chromogranin. In all fifteen adenomas squamoid morules were negative for Ki- 67.

Conclusion
Squamoid morules are characterized by strong male predominance, association with large adenoma size, beta-catenin nuclear positivity, CK5/6 expression, and no Ki-67 expression. Beta-catenin nuclear expression is helpful in distinguishing squamoid morules from foci of microinvasion.
Challenges in Diagnosis of Steatohepatitic Hepatocellular Carcinoma on a Biopsy Specimen
Authors: Amin S E , Elzamly S , Ibrahim N , Zhang H 
Published: November 2023

Abstract

Introduction/Objective
Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Steatohepatitic hepatocellular carcinoma (SH-HCC) is a subtype that is associated with metabolic syndrome and alcoholic hepatitis. Diagnosing SH-HCC can be extremely challenging on a biopsy specimen, given that steatohepatitis-like changes can be seen in focal nodular hyperplasia and hepatic adenoma. Herein, we present a very challenging case of SH-HCC that was initially diagnosed as a well-differentiated lesion after multi-institutional consultations.

Methods/Case Report
A 54-year-old female with past medical history of diabetes and hypertension presented with flank pain and a 2.7 cm liver mass in a background of diffuse hepatic steatosis by CT scan, concerning for malignancy. Viral hepatitis serology workup was negative.

Results (if a Case Study enter NA)
The liver core biopsy reveals a well-differentiated hepatic lesion with areas of steatosis, fibrosis, and features of steatohepatitic changes including ballooning hepatocytes and Mallory-Denk bodies. No significant cytological atypia is identified. No definitive loss of reticulin is seen by reticulin stain. The cytological or architectural atypia was insufficient in isolation to diagnose HCC. The lesion cells are positive for HepPar-1 and Arginase-1, while negative for Glypican. Diffuse sinusoidal CD34 staining is present. Ki-67 proliferative index is approximately 2%. These changes did not permit a confident diagnosis of hepatic adenoma or hepatocellular carcinoma. The case was sent for consultation by multiple institutions with a consensus diagnosis of well-differentiated hepatic lesion/neoplasm. A follow-up liver wedge resection shows a hepatic neoplasm with areas of loss of reticulin staining. Focal stromal invasion is present. The neoplastic cells are positive for HepPar-1, Arginase-1, glutamine synthetase and Glypican (patchy). Final diagnose was rendered as SH-HCC.

Conclusion
The diagnosis of SH-HCC requires high level of suspicion on a biopsy specimen, especially in a background of steatohepatitis. A reticulin stain and immunohistochemical stains may not be helpful. Clinical- radiological correlation should always be considered.
Pathologic examination of ectopic pancreatic tissue in the gallbladder: A case report
Authors: Demetrious M G 
Published: November 2023

Abstract

Introduction/Objective
Ectopic pancreatic tissue (EPT) is an entity defined by the presence of pancreatic tissue at its non-physiological site, while co-existing with original tissue in its correct anatomical location. While EPT is a rare process in locations such as the stomach, duodenum, and esophagus; it is even more uncommon for it to occur in the gallbladder. To our knowledge, fewer than thirty cases of EPT in the gallbladder have been reported. The following case report presents a 47-year-old woman with ectopic pancreatic tissue in the gallbladder.

Methods/Case Report
A 47-year-old female presented to our emergency department with her third episode of colicky right upper quadrant pain. Ultrasound imaging demonstrated cholelithiasis with additional ill-defined findings of the gallbladder wall, which included but were not limited to acute emphysematous cholecystitis and chronic cholecystitis with features of porcelain gallbladder. Laparoscopic cholecystectomy was performed without complications.
Pathologic evaluation of the specimen demonstrated a cystic structure at the fundus of the gallbladder with coexisting EPT, fundic-type adenomyomatosis, and cholelithiasis.

Results (if a Case Study enter NA)
NA

Conclusion
Ectopic pancreatic tissue is a rare incidental finding which is often confused for a malignant process. While it is more commonly seen in the gastrointestinal tract from the esophagus to the duodenum, it can present in other sites such as in this case. Currently, there is no specific imaging method to determine the presence of EPT. Ultrasonography is nonspecific and EPT can be confused for a number of conditions ranging from benign to malignant. Gross examination is fairly unremarkable, however microscopic examination is a straightforward diagnosis. While it is a benign process, malignant transformation can occur and pathologists should be aware of this possibility. For this reason, additional sections may be recommended to rule out occult malignancy.
Comparison of INSM1 immunostaining with established neuroendocrine markers Synaptophysin and Chromogranin A in over 14,000 neuroendocrine and non-neuroendocrine tumors
Authors: Möller K , Gorbokon N , Hube-Magg C , Fraune C , Lennartz M , Blessin N C , Sauter G , Simon R , Minner S , Krech T , Marx A H 
Published: November 2023

Abstract

Introduction/Objective
INSM1 is a transcription factor protein which is increasingly used as an immunohistochemical marker for neuroendocrine differentiation.

Methods/Case Report
To determine the prevalence of INSM1 expression in tumors and its expression pattern in normal tissues, tissue microarrays containing 14,908 samples from 117 different tumor types/subtypes as well as 76 different normal tissues were analyzed by immunohistochemistry.

Results (if a Case Study enter NA)
INSM1 was positive in 89.2% of 471 neuroendocrine neoplasms (NEN) and in 3.5% of 11,815 non-neuroendocrine neoplasms that were successfully analyzed. INSM1 positivity occurred in 59 non- neuroendocrine tumor entities, of which 15 entities contained at least one strongly positive case. Comparison with synaptophysin and chromogranin A revealed that in NEN, synaptophysin showed the highest sensitivity (93.3%), followed by INSM1 (89.2%) and chromogranin A (87.5%). In neuroendocrine carcinomas (NEC), sensitivity was highest for INSM1 (88.0%), followed by synaptophysin (86.5%) and chromogranin A (66.4%). The additional use of INSM1 increased the sensitivity for detecting neuroendocrine differentiation in NEN from 88.2% (synaptophysin and chromogranin A) to 91.2% (synaptophysin, chromogranin A and INSM1).

Conclusion
Our study shows that INSM1 is a useful additional marker for neuroendocrine differentiation that shows a particularly high sensitivity in NEC. The additional use of INSM1 results in a higher sensitivity for the identification of a neuroendocrine differentiation than what can be obtained by using only synaptophysin and chromogranin A.
A Case of Recurrent Gastrointestinal Stromal Tumor with Chondroid Differentiation
Authors: Le P , Monika F , Kovar J 
Published: November 2023

Abstract

Introduction/Objective
Gastrointestinal stromal tumors (GIST) comprise 0.1% to 3% of gastrointestinal neoplasms but are the most common mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and most frequently arise in the stomach. However, chondroid differentiation of GIST is extremely rare with less than ten cases reported in the literature. We present a case of a 58-year-old female with recurrent GIST post-imatinib therapy.

Methods/Case Report
The patient was originally diagnosed with GIST seven years prior when she visited the Emergency Department after a syncopal episode and was incidentally found to have a 11 x 8.5 x 7 cm gastric mass based on abdominal CT scan. She underwent biopsy that showed spindle cell lesion staining positively for DOG1 and CD117 and negatively for desmin, consistent with GIST. She subsequently underwent partial gastrectomy with pathology showing high grade spindle cell type GIST with focal bizarre epithelioid cells and necrosis. Molecular testing identified the tumor to have a c-KIT mutation. Based on large tumor size and risk of recurrence, she was treated with imatinib for three years. Two years after completion of imatinib therapy, her surveillance imaging showed a mass compatible with recurrence measuring 11.8 x 11.7 x 6.7 cm. Additionally, imaging identified a mass in her mid abdomen that was biopsied and showed metastatic GIST supported by immunophenotype.
The patient undewent a second partial gastrectomy and the mass on gross examination showed a heterogeneous cut surface displaying some solid and necrotic areas that appears to have invaded adjacent adipose tissue.
Histomorphological features showed a spindle component with necrosis and a focus of chondroid differentiation. Tumor cells were immunopositive for DOG1 and CD117. The chondroid component did not stain for either marker.

Results (if a Case Study enter NA)
NA

Conclusion
There have been few reported cases of GIST with chondroid differentiation. Moreover, a previous study found three of 35 patients who showed phenotypic alteration post-imatinib therapy with changes ranging from tubulopapillary to epithelioid morphology. However, there has been no case with chondroid differentiation after imatinib therapy reported. This case illustrates the variable response of GIST to imatinib and its possible transformation because of the therapy. To better understand the prognosis of GIST with chondroid differentiation, more cases should be identified, reported, and monitored closely.
Synovial Sarcoma of the Descending Colon: Report of a Rare Case and Review of the Literature
Authors: Khan A , Rishi A , Chang C , Vitkovski T , Savant D , Soundararajan S , Thomas R , Torrence D , Zhao Y 
Published: November 2023

Abstract

Introduction/Objective
Synovial Sarcoma is a mesenchymal malignancy that occurs primarily in the deep soft tissue near large joints of the extremities in young adults. Synovial sarcoma of the gastrointestinal tract is extremely rare. There is not enough literature to establish a consensus on management and treatment for colorectal synovial sarcoma.

Methods/Case Report
An 85-year-old male preresented with a positive cologuard test and the colonoscopy revealed a 12 mm polyp in the descending colon. Polypectomy was preformed. Histological examination exhibits spindle cell proliferation with fascicular growth pattern and with small nucleoli. There are collagen deposition, variable size of thick wall vessels and mixed inflammatory cells including lymphocytes, eosinophils and neutrophils in the background.
Mitosis are identified. Immunohistochemical stains show tumor cells are negative for CD34, S100, DOG1, CD117, STAT6, Bcl-2, Desmin, and AE1/AE3, and focal positive for EMA, SMA and ALK. Immunohistochemical stain for SS18-SSX fusion protein is positive. Archer fusionplex targeted RNA sequencing (M23-1377) showed SS18:SSX2 fusion. A structural genomic alteration between the SS18 and SSX2 genes is detected [t(18;X)(q12.1;p11.22)]. These findings confirmed the diagnosis of synovial sarcoma.

Results (if a Case Study enter NA)
NA

Conclusion
Here we report a rare case of descending colon primary synovial sarcoma. Synovial sarcoma is generally considered as an aggressive and high-grade lesion with metastatic potential and its management is different from other colorectal neoplasms. This case report emphasies a wide differential diagnosis for colorectal lesions and prompt diagnosis and early management is important for better patient outcome.
Russell body gastritis: a case series and review of literature
Authors: Arackal A , Sonawane S S , Guzman G 
Published: November 2023

Abstract

Introduction/Objective
Russell body gastritis is considered a rare finding characterized by Russell body-containing plasma cells in the lamina propria. Patients typically present with nonspecific findings. In this study, clinical and histopathological features of 3 cases with incidental findings of Russell body gastritis (RBG).&lt;quillbot-extension- portal&gt;&lt;/quillbot-extension-portal&gt;

Methods/Case Report
The Epic SlicerDicer tool was used to identify institutional cases between April 2022 to April 2023 using the keyword “Russell Body”.
Using the PubMed database, we searched for articles published between January 2003 and April 2023, with the keyword "Russell body gastritis". Studies that described novel RBG cases were included.&lt;quillbot-extension- portal&gt;&lt;/quillbot-extension-portal&gt;

Results (if a Case Study enter NA)
The three cases were female with a mean age of 47 (42-51). Two patients were presented with chronic dyspepsia and one patient was being evaluated for right upper quadrant pain. The endoscopic finding for one patient was significant for multifocal erythematous gastric mucosa and the other two patients had unremarkable findings. Biopsies from the three patients revealed active gastritis in 2 cases and inactive chronic gastritis in 1 case. A dense accumulation of plasma cells with Mott cells and Russell bodies were identified in the lamina propria. Helicobacter pylori was identified on H. pylori stain in one case. Upon further investigation, CD138 highlights the plasma cells and kappa and lambda ISH demonstrated polyclonal plasma cells and cytokeratin AE1:AE3 was negative for a carcinoma
A review of 64 previously reported cases of RBG shows that the average age of presentation is 63. Half of the cases were associated with Helicobacter pylori infection. Other associated conditions include multiple myeloma (3%) and HIV (6%). There have been 12 cases with monoclonal plasma cells with 10 cases of kappa-type monoclonality (including one case of duodenitis) and 1 case of lambda-type monoclonality.&lt;quillbot-extension-portal&gt;&lt;/quillbot- extension-portal&gt;

Conclusion
Most cases of RBG have been linked with helicobacter pylori. However, the underlying etiology is not well understood. Differentials include plasmacytoma, MALToma, and signet ring carcinoma. The clinical significance and its long-term effect remain unknown. Our report is the largest review of RBG. With its wide range of clinical presentations, additional cases are to define this entity better.&lt;quillbot-extension-portal&gt;&lt;/quillbot-extension-portal&gt;
Colonic Malakoplakia in Renal Transplant Patient: Case Report and Literature Review
Authors: Garzon S , Arackal A , Zaidi A , Abdalla S 
Published: November 2023

Abstract

Introduction/Objective
Malakoplakia is a relatively rare inflammatory condition defined by histiocytic infiltration with pathognomonic intracytoplasmic inclusions known as Michaelis-Gutmann bodies. The lesion has been strongly associated with immunosuppressed states. Although the exact mechanism is unknown, an infectious component, such as impaired bactericidal activity in macrophages is highly implicated which leads to deposition of calcium and iron on residual bacterial glycolipid. Although commonly identified in the genitourinary tract, malakoplakia has been found in virtually all organ systems.

Methods/Case Report
We hereby present a 44-year-old male with a history of renal transplantation, presenting with a history of chronic diarrhea for one year. Colonoscopy was performed which identified diverticulosis in the sigmoid colon and a 5 mm sessile rectal polyp. Histopathological examination of the polyp biopsy demonstrated chronic active colitis, histiocyte aggregates and numerous intracellular, basophilic, concentric, laminated and targetoid calcified structures that were highlighted by Von Kossa and iron stains. These structures are known as Michaelis-Gutmann bodies which are pathognomonic of malakoplakia. A literature review of 45 cases was completed by utilizing the PubMed database. The cases reviewed included involvement of the allograft, host kidney, bladder, colon, prostate, thyroid, submandibular gland, lung, and testicles. Many of the patients were managed with either long term antibiotics, reduction of immunosuppression, or excision of the lesion with improvement in symptoms and/or renal function.

Results (if a Case Study enter NA)
NA

Conclusion
Our case highlights the importance of diagnosing this benign entity on histology examination to allow early treatment and improvement in symptoms.