bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver Metastasis Masking as Neuroendocrine Carcinoma (NEC) Predates Discovery of Intra/Peri-Thyroid Thymic Carcinoma (ITTC)
Authors: Agyapong Y O , Zaidi A , Sonawane S S , Guzman G , Sheikh U 
Published: October 2024

Abstract

Introduction/Objective
Intrathyroidal thymic carcinoma (ITTC) also known as Carcinoma showing Thymus-Like differentiation (CASTLE) is a rare malignancy comprising 0.1 to 0.15% of thyroid cancers. The WHO 5th Edition emphasizes that these tumors may also occur outside the thyroid typically at the lower pole

Methods/Case Report
Our aim is to show that NEC is a mimic of ITTC; that CD5, c-KIT (CD 117), p40, CK5/6 expression distinguishes ITTC from NEC, and that ITTC may at times express NE markers. Briefly, a 51-year-old man presented with hoarseness left neck mass and a PET avid liver lesion in 2016. Biopsy of the neck and liver masses revealed an infiltrating poorly differentiated “NEC” with similar morphology; positive for p53, chromogranin, and synaptophysin; negative for cam5.2, thyroglobulin, TTF-1, CD20, Pax5, CD3, CD5, S-100, calcitonin, CD56, p16, p63, c-KIT (CD117), AE1/3; and 100% staining for Ki-67. The patient underwent chemotherapy, responded well, remained under surveillance, and was symptom-free in the interim. A new 2.1 x 2.0 cm nodule appeared at the left thyroid lower pole after 6 years. The tumor was positive for CD5, CD117, p40, CK5/6, with &gt; 95% Ki67 expression. Chromogranin, synaptophysin, CD56, thyroglobulin, calponin, TTF1, and Epstein Barr virus were negative and was overall diagnostic of ITTC

Results (if a Case Study enter NA)
NA

Conclusion
This shows the diagnostic dilemma of distinguishing ITTC from NEC which may share expression of neuroendocrine (NEC) markers and that positivity for CD5, c-KIT (CD117), p40, and CK5/6 are key diagnostic features of ITTC.
Teratoid hepatoblastoma with small cell undifferentiated histology in polysplenia patient: a case report
Authors: Tran T M , Mohamed R , Saulino D M , Bui C M 
Published: October 2024

Abstract

Introduction/Objective
Hepatoblastoma (HB) with teratoid is a uncommon variant of mixed epithelial and mesenchymal components. Conversely, HB with small cell undifferentiated (SCUD) is extremely rare, with only nine documented cases showing retained INI-1 expression in the literature. The prognosis of SCUD remains debatable. In this report, we describe the first case of combined teratoid HB with a SCUD component that preserved INI-1 expression with a favorable outcome.

Methods/Case Report
A 2-year-old girl with polysplenia syndrome presented with a right liver mass detected during ultrasound screening. The alpha fetoprotein levels were significantly elevated to 148,000. MRI revealed a 7.2 cm lesion, staged as Pre-Treatment Extent 2 (PRETEXT) in the right anterior liver. She underwent cholecystectomy and right hepatectomy. Resection specimen revealed a mixed neoplasm comprising epithelial components (fetal and embryonal) and mesenchymal components. Additionally, notable findings include small cell component and teratoid features, characterized by melanin pigment and neuroectodermal elements. All the neoplastic cells showed reactivity with CD34, reticulin, SALL4, beta-catenin, GPC-3, arginase-1, chromogranin, and glutamine synthetase. Notably, the teratoid area only displayed positivity for CD56 and NSE, while vimentin highlighted capillaries, vessels and focally staining small cells. Furthermore, CK19 highlighted the small cell components and the bile ducts in the background liver. Importantly, INI-1 staining was retained in all tumor cells, including the small cell component. Synaptophysin and Prussian blue were negative in all lesional cells. After a 2-year follow-up, no recurrence was observed.

Results (if a Case Study enter NA)
NA

Conclusion
This case underscores the diagnostic challenge posed by small cell undifferentiated (SCUD) hepatoblastoma. Moreover, it contributes to the understanding of this rare variant of hepatoblastoma and suggests a potential favorable prognosis associated with retained INI-1 staining in the SCUD component.
Gastric Epithelial Neoplasm of Fundic-Gland Mucosa Lineage: Showed the Same Genetic Lineage and Ki67 May Help in Their Identification
Authors: li H 
Published: October 2024

Abstract

Introduction/Objective
Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare form of gastric tumors that encompasses oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the clinicopathologica and molecular characteristics of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms.

Methods/Case Report
The NGS and immunohistochemical staining were performed on 37 cases diagnosed with GEN-FGMLs with a thorough histological evaluation. Gene alternations were analysed and compared across histological subtypes. we used an artificial intelligence approach for the recognition of the Ki67 immunohistochemistry stained.

Results (if a Case Study enter NA)
The patient’s ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified.
Histopathological similarities exist between GEN-FGMLs. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view (p&lt;0.05) and had larger sizes (p&lt;0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA (p&lt;0.0001). The heterogeneity of mutational signatures, somatic mutations, and copy number variations was revealed across histological subtypes. The top five mutational signatures in OGA were ROS1, CTNNA1, GNAS, BRCA2, and ZFHX3. The top five mutational signatures in GA-FG and GA-FGM were GNAS, MLL3, BRAF, MSH3, and EGFR. GNAS were both found in OGA, GA-FG and GA-FGM. Compared with well-differencent gastric adenocarcinoma, The top five mutational signatures in GEN-FGMLs were GNAS, BRAF, ROS1, MLL3, and MSH3. Recurrently mutated key signaling pathways across tumor types in GEN-FGML were Wnt signaling pathways.

Conclusion
GEN-FGMLs are a group of well-differentiated gastric tumors with favourable biological behaviours. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. GEN-FGMLs showed the same genetic lineage, the Wnt signalling pathway plays a role in the development and progression of GEN-FGMLs.
Expression of human epidermal growth factor receptor 2 (HER2) in colorectal cancer and its correlation with clinicopathological characteristic among Jordanian patients
Authors: Sughayer M A , Atieh Z , Obeidat M 
Published: October 2024

Abstract

Introduction/Objective
Human epidermal growth factor receptor 2 (HER2/neu) is a well-established therapeutic target in breast and gastric cancers. Currently HER2 expression is being considered in other solid tumors including colorectal cancer (CRC). We aimed to investigate HER2 expression in CRC among Jordanians and its association with clinicopathological variables.

Methods/Case Report
Formalin-fixed, paraffin-embedded tissue blocks of 69 CRC cases were retrieved with their clinicopathological data. Tissue microarray (TMA) were constructed and immunostained using anti-HER2/neu 4B5 monoclonal antibody (Ventana, Tucson, AZ). HER2 scoring was performed by two experienced pathologists using the HERACLES criteria (HER2 positivity: cases of (3+) in ≥10% of cells and FISH-positive equivocal cases). Fisher’s exact/Chi-square test was used to investigate the association between HER2 s and clinicopathological data such as age, gender, histological differentiation, node and metastasis (NM) stage, and tumor site. Survival analysis was evaluated using Kaplan–Meier curves.

Results (if a Case Study enter NA)
Any degree (score) of HER2/neu expression was seen in 43.5 % of the cases. In 25 (36.2%), 4 (5.8%) and 1 (1.5%) the HER2 score was 1+, 2+ and 3+ respectively. The rest of the cases, 39 (56.5%) were scored as 0. Two of the four cases with a score (2+) required ISH testing to confirm amplification which was not performed. No significant association was found between HER2/neu expression and clinicopathological parameters or with survival. However, survival analysis showed that combined 2+/ 3+ group tend to have worse overall (OS) and event -free survival than the (0/1+) group.

Conclusion
The prevalence of HER2 overexpression in CRC is low among Jordanian patients, with only 1.5% of the study sample exhibiting definite HER2 overexpression. This rate is lower than the 3-5% rate reported in general, however the small sample size and lack of FISH confirmation might have contributed to this low rate. There was a trend towards worse OS and EFS in HER2 positive cases
The umblicus says it all
Authors: Bandara K , Facile E , Lankachandra K , Galbraith R 
Published: October 2024

Abstract

Introduction/Objective
Umbilical nodules can be divided into benign and malignant. Malignant lesions of the umbilicus are very rare. They can arise from primary tumors or secondary to abdominal and pelvic malignancies. Literature review suggests that these umbilical lesions can present as primary tumor in 38% of the cases, endometriosis in 32%, and metastatic lesions in 30%. Umbilical metastasis is one of the main characteristic signs of extensive neoplastic disease and is known as Sister Mary Joseph’s nodule (SMJN). It is a very rare finding and the incidence of SMJN is 1- 3% in people diagnosed with intra-abdominal or pelvic malignancies.

Methods/Case Report
A 31-year-old male with no past medical history presented to the emergency room with 3 months history of umbilical nodule and 60 pounds weight loss. He experienced early satiety, abdominal pain, nausea and generalized fatigue. CT abdomen showed hepatomegaly with numerous hypoattenuating lesions throughout the liver with peripheral enhancement, and hypoattenuating mass within the pancreatic tail and body measuring approximately 2.1 x 5.8 cm that appears contiguous with hilar splenic lesion. CT chest showed multiple pulmonary metastases with prominent precarinal and subcarinal lymph nodes. Serologic tests revealed elevated Alpha fetoprotein, ALP, ALT, and CA19-9. Patient underwent umbilical nodule core biopsy and right liver core biopsy.
Microscopic evaluation of the specimens revealed pancreatic acinic cell carcinoma with two different morphological variants. Umbilical nodule with glandular pattern and liver lesion with trabecular pattern. Immunohistochemical stains were performed with tumor cells positive for CK 7, Trypsin and BCL-10 and negative for Glypican 3, CK 20, AFP and CD56. The prognosis is poor, with an average survival time of about 19 months. After the diagnosis patient underwent chemotherapy.

Results (if a Case Study enter NA)
NA

Conclusion
Umbilical nodules can be diagnosed with careful clinical and histopathological evaluation. The prognosis of patients presenting with SMJN is generally poor as it is a sign of advanced malignancy. Sometimes it may be the first and only sign of an internal neoplasm. Therefore, this is an important differential diagnosis to consider.
Navigating the HER2 Frontier: Advancing Gastrointestinal Adenocarcinoma Diagnosis through Updated NCCN Guidelines
Authors: Kumar D , Kiran F , Rao D 
Published: October 2024

Abstract

Introduction/Objective
HER2-status is routinely tested in breast and upper-gastrointestinal (GI) cancers. Studies have shown the importance of anti-HER2 therapy with HER2 being a negative predictive marker in advanced colorectal cancer (CRC). Thus, recent NCCN-guidelines recommend screening for HER2-status in such cases. To increase compliance with the NCCN recommendations, we performed a quality assurance project to screen for HER2 status by immunohistochemistry (IHC) in GI adenocarcinomas.

Methods/Case Report
We conducted a validation of HER2 IHC for GI adenocarcinomas. Surgical pathologists were informed via email discussing the criteria and significance of HER2 IHC in GI adenocarcinomas. A total of 50 GI adenocarcinoma cases were evaluated in our surgical-pathology service, from June to December 2023. Pathologists were periodically reminded, either through email or in-person meetings, to ensure HER2 IHC assessment, especially for cases initially missed.

Results (if a Case Study enter NA)
Out of 50 GI adenocarcinomas, HER2 IHC was performed on 27 out of 50 cases (54%) without any reminder. The pathologists were reminded to perform HER2 IHC on the remaining 23 cases, resulting in the IHC performance on an additional 22 cases, giving a yield of 98%. Of 49 cases, HER2 was negative in 46 cases and was positive (3+) in one case, and equivocal (2+) in two cases. Subsequent HER2 FISH analysis of equivocal cases showed HER2 amplification in one case. Thus, HER2 expression/amplification was present in 2 out of 50 cases (4%) including one case each in upper and lower GI tracts.

Conclusion
While we have long recognized importance of HER2 Status in upper GI adenocarcinomas, it’s now clear that understanding HER2 status is crucial in CRC too. New evidence highlights how anti-HER2 therapy can make a difference, especially for advanced cases. By screening for HER2 early, clinicians can enroll such patients in appropriate clinical trials and also guide them on the appropriate treatment options, offering hope and targeted care.
Crashing into Discovery: Nesidioblastosis in Adult, Unmasked post-Motor Vehicle Accident - A Case Study and Literature Review
Authors: Mohammed I , Rao D 
Published: October 2024

Abstract

Introduction/Objective
Nesidioblastosis, characterized by pancreatic duct-derived B-islet cell proliferation, typically manifests with hypoglycemic symptoms. While more common in newborns, it can rarely affect adults. Here, we report an incidental finding of nesidioblastosis in a 37-year-old female following abdominal trauma due to a motor vehicle crash (MVC).

Methods/Case Report
A 37-year-old female with no notable medical history presented with blunt abdominal trauma following an MVC. The emergency evaluation revealed a grade 4 traumatic splenic laceration and severe hemoperitoneum. Preoperative lab results showed decreased hemoglobin, elevated white cell count, prolonged prothrombin time, and reduced calcium and magnesium levels. The patient underwent a splenectomy along with a distal pancreatectomy. While grossly unremarkable, microscopic examination revealed maintained acinar architecture with focal hyperplasia around pancreatic ducts. Enlarged acinar cells with pleomorphic nuclei and prominent nucleoli were consistent with focal nesidioblastosis.

Results (if a Case Study enter NA)
NA

Conclusion
Multiple studies have documented the first reported case of nesidioblastosis in adults was in 1975. While its exact incidence is uncertain, most sources suggest a relative frequency of 0.5 – 7% of persistent hyperinsulinemic hypoglycemia, with estimated overall an annual rate of around 9 per 100,000, with a higher occurrence among females. This unusual incidental discovery of nesidioblastosis in an asymptomatic patient undergoing pancreatic resection for unrelated reasons highlights the likelihood of underestimating the actual prevalence of this disease.
Characterizing POLE Mutation-Associated Colorectal Carcinoma: Clinical and Pathologic Insight
Authors: Mohammed I , Rao D 
Published: October 2024

Abstract

Introduction/Objective
Colorectal carcinoma (CRC) is one of the most common cancers and a leading cause of cancer-related death in the United States. Pathogenically, colorectal carcinoma is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alteration. Identification of DNA polymerase mutation leads to the characterization of a new molecular pathway of carcinogenesis named the POLE pathway.

Methods/Case Report
Utilizing the cBioportal platform and Cancer Genome Atlas (TCGA) Firehouse Legacy data, we identified 118 cases of CRC with mutations in the POLE gene. We evaluated the various clinical and pathologic features of POLE mutation-associated CRC.

Results (if a Case Study enter NA)
Within the cohort of 118 cases linked to mutations in the POLE gene, gender distribution reveals that 63 individuals, comprising 53.8% of the sample, are male, while 42 individuals, accounting for 35.9%, are female. Ethnicity breakdown showcases a predominantly White population, with 92 cases (78.6%), followed by 8 cases (6.8%) attributed to Asian-Far East/Indian Subcontinent descent, 5 cases (4.3%) categorized as Asian, and 4 cases (3.4%) each identified as Black and Black or African American. Additionally, one case (0.9%) has an unknown ethnicity, while 4 cases (3.4%) have unspecified racial backgrounds.
The average age at diagnosis is recorded at 48.5 years, with ages ranging from 25 to 85, signifying a broad age spectrum within the affected population. Delving into cancer subtypes, the majority of cases, constituting 64 instances (54.2%), manifest as colon adenocarcinoma, while 38 cases (32.2%) present as rectal adenocarcinoma. Moreover, 9 cases (7.6%) are characterized as colorectal adenocarcinoma, 6 cases (5.1%) are classified as mucinous adenocarcinoma of the colon and rectum, and one case (0.8%) manifests as medullary adenocarcinoma of the colon. This detailed elucidation provides a comprehensive understanding of the demographics and clinical presentation within the cohort affected by POLE gene mutations.

Conclusion
In summary, our research has meticulously examined 118 instances of colorectal carcinoma (CRC) intricately linked to mutations in the POLE gene. Within this cohort, a predominant demographic emerges, with a notable prevalence among individuals of White ethnicity. Delving deeper into the pathological spectrum, colon adenocarcinoma emerges as the prevailing subtype, exemplifying the intricate interplay between genetic aberrations and cancer manifestation.
The Great Mimicker: Goblet Cell Adenocarcinoma of the Appendix Mimicking Mammary Carcinoma in a Patient with a History of Metastatic Breast Cancer
Authors: Zhou X , Du W , Husson M 
Published: October 2024

Abstract

Introduction/Objective
Goblet cell adenocarcinoma of the appendix is a rare and aggressive malignancy with high- grade histological patterns that pose diagnostic challenges due to their resemblance to other tumors. Previous reports have indicated that high-grade goblet cell adenocarcinoma may exhibit similarities to well-differentiated neuroendocrine tumors, and metastatic high-grade goblet cell adenocarcinoma can manifest diverse histologic growth patterns within a single section.

Methods/Case Report
We present a case of an 82-year-old female with a known history of breast cancer with sacral metastasis, presenting with a left upper quadrant “pinching” sensation. Histopathological examination following colectomy showed features of metastatic mammary carcinoma with mixed lobular (pleomorphic and partial signet ring cell type) and ductal features (Figure 1); Notably, different histologic patterns were observed in two tumor deposits, highlighting the complexity of the diagnosis (Figure 2). However, further investigation of the tip of the appendix revealed goblet-like mucinous cells arranged in a tubular growth pattern (Figure 3). Immunohistochemical stains were performed with adequate controls, revealing positive staining for CK20, SATB2, and CDX2, while showing negativity for BRST2, SATB2, GATA3, CK7, PR, ER, and HER2 (Figure 4). These findings corroborate the diagnosis of goblet cell adenocarcinoma.

Results (if a Case Study enter NA)
NA

Conclusion
In our case, we observed morphological features of goblet cell adenocarcinoma that overlapped with those of established mammary carcinomas. This scenario underscores the diagnostic challenges posed by rare tumors and emphasizes the significance of identifying the low-grade component of goblet cell adenocarcinoma, particularly in patients with a history of metastatic breast cancer.
An unusual liver tumor with challenging morphologic features and immunophenotype: A case report of metastatic HPV-driven basaloid anal squamous cell carcinoma
Authors: Beeter M C , Dhingra S , Amrikachi M , Thrall M 
Published: October 2024

Abstract

Introduction/Objective
Basaloid squamous cell carcinoma (BSCC), a rare subtype of squamous cell carcinoma, occurs most commonly in esophagus, lungs, and head and neck. Anal BSCC is extremely rare and has a 10-20% rate of metastasis. High-risk HPV (HR-HPV) is the main causative agent. BSCC occurrence in an atypical site without a known primary tumor, and with atypical immunoprofile can be a diagnostic challenge.

Methods/Case Report
We report an 83-year-old female with history of breast carcinoma who presented for worsening chest pain. Imaging studies showed pulmonary nodules, 1.8 cm hepatic mass, and pelvic nodules. Liver biopsy showed infiltrating nests of carcinoma with solid and cribriform patterns and luminal necrosis. Some tumor nests had basaloid features with peripheral palisading. Tumor was positive for CK7 and pankeratin; and negative for ER, SOX10, GATA3, GCDFP-15 (Breast markers), CDX2 (GI marker), P63 and P40 (squamous markers), INSM1, Synaptophysin (Neuroendocrine) and TTF1 (lung adenocarcinoma). There was microfocal staining with CK20 and SATB2. Tumor morphology and immunophenotype were not entirely specific to the site of origin. Further search into patient’s medical history showed a recent anal mucosal biopsy revealing a high-grade squamous epithelial lesion with diffuse P16 reactivity. The slides for the anal lesion were reviewed and showed morphologic features similar to the liver biopsy. Additional studies showed both tumors were positive for HR-HPV ISH, P16 (diffuse), and CK5/6 (patchy); and negative for P63. The morphologic features and immunoprofile were supportive of metastasis from HPV-driven BSCC of anus. Subsequent PET Scan revealed a rectal/anal mass.

Results (if a Case Study enter NA)
NA

Conclusion
For tumors with unusual morphology and immunophenotype, complete medical history review, and communication with clinician are important tools in achieving correct diagnosis. HR-HPV ISH is a new tool that can be very useful in reaching correct diagnosis in metastatic anogenital or oropharyngeal squamous carcinomas with basaloid features.