bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPS1 is a highly sensitive marker for breast cancer: A tissue microarray study evaluating more than 19,000 tumors from 152 different tumor entities
Authors: Lennartz M , Blessin N C , Hube-Magg C , Sauter G , Simon R , Dum D , Minner S , Clauditz T S , Bernreuther C , Steurer S , Lebok P
Published: November 2023

Introduction/Objective

TRPS1 (Trichorhinophalangeal syndrome 1) is a nuclear protein expressed in breast epithelial cells. TRPS1 immunohistochemistry (IHC) has thus been suggested as a marker for breast cancer. However, reports on TRPS1 positivity in other cancer types are piling up.

Methods/Case Report

To comprehensively determine the diagnostic utility of TRPS1 IHC, tissue microarrays containing 19,201 samples from 152 different tumor types and subtypes were analyzed. GATA3 IHC data were available from 11,891 of these tumors from a previous study.

Results (if a Case Study enter NA)

TRPS1 positivity occurred in 86 of 152 tumor categories of which 36 contained at least one strongly positive case. TRPS1 staining predominated in various types of breast carcinomas (51%-100%) and was also seen in various subtypes of soft tissue tumors (up to 100%), salivary gland tumors (up to 46%), squamous cell carcinomas (up to 35%), and gynecological cancers (up to 40%) as well as in other tumors. TRPS1 positivity occurred in only 1.8% of 1,083 urothelial neoplasms. Positivity for both TRPS1 and GATA3 occurred in 47.4%-100% of breast cancers, up to 30% of salivary gland tumors, but in only 29 (0.3%) of 9,835 tumors from 134 other cancer entities.

Conclusion

Although TRPS1 expression can be seen in many different tumor types, TRPS1 Immunohistochemistry has high utility for the identification of cancers of breast or salivary gland origin, especially in combination with GATA3. The virtual absence of TRPS1 positivity in urothelial neoplasms is useful for the distinction of GATA3 positive urothelial carcinoma from breast cancer.
Proposed New Cutoff Value for Troponin in the Diagnosis of Acute Myocardial Infarction (AMI) in Patients with Congestive Heart Failure (CHF) and/or End Stage Renal Disease (ESRD)
Authors: Gabutan E , Minkowitz J , Guzman J C , Steimetz E , Seydafkan S , Pincus M R
Published: November 2023

Introduction/Objective

In a recent publication, we assessed the efficacy of two serum biomarkers for AMI, cardiac Troponin I (cTnI) and creatine kinase-MB (CK-MB), for patients presenting to our emergency department (ED) with acute chest pain. We found that two conditions, CHF and ESRD in 85 patients, caused a significant number of false positive results that resulted in lowering the specificity and positive predictive value of both tests, which were already reduced by the low prevalence of AMI in our patient population. Removal of these patients resulted in significant increases in the two latter parameters. In this study, we focus on cTnI to determine if changing the cutoff value can increase the sensitivity and specificity of diagnosing acute MI in patients with CHF and ESRD.

Methods/Case Report

A cohort of 380 patients who presented with acute chest pain in the ED and worked up for acute MI were included, 85 of whom had CHF and/or ESRD. A total of 47 patients (15.4% prevalence) were definitively diagnosed with AMI. An initial serum cTnI sample was collected for each patient. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were then compared using the routine cutoff cTnI value (0.05 ng/mL) and the higher cutoff of 0.2 ng/mL.

Results (if a Case Study enter NA)

Using the original cutoff of 0.05 ng/mL for cTnI in the patients with CHF or ESRD, the sensitivity and NPV were both 100%, while the specificity and PPV were low at 40.3% and 23%, respectively.

Interestingly, when the cutoff was raised from 0.05 to 0.2 ng/mL, the sensitivity decreased by about 8% to 92.3 (12 out of 13 patients with AMI), and the specificity increased almost two-fold to 76.4%. The PPV increased to 40.4% and NPV was 98.2%. These values are comparable with the sensitivity, specificity, PPV and NPV of the total population at 85.3%, 82.4%, 38.7% and 97.7%, respectively.

Conclusion

The original cutoff value for cTnI in patients with ESRD and CHF produces a very low specificity and PPV. The results of this study suggest that an acceptable cutoff for cTnI to rule-out AMI patients who have CHF and or ESRD is 0.2 ng/mL which is four times higher than the original, but has comparable specificity, sensitivity, PPV and PPV to the total patient population. We note that this study must be regarded as a pilot study since the numbers of patients are small. We recommend a larger study to determine the validity of these conclusions.
Green Synthesis of Bioconjugated Magnetic Nanoparticles (MNPs) By Punica granatum And Its Applications As Anti-microbial Agent
Authors: Abdelmonem M , Wasim H , Eldaly R , Abdelmageed M
Published: November 2023

Introduction

In recent years, the development of efficient green chemistry methods for synthesizing metal nanoparticles has become a major focus of many researchers. Nanoparticles produced by plants are more stable, and the rate of synthesis is faster than in the case of microorganisms.

Methods/Case Report

Objectives: Synthesis of (MNPs) by Punica granatum, confirming the formation that it exists, and studying their antibacterial activity effects.

Materials and methods

By using the Pomegranate plant, drying the plant 200 g (hot oven/sun), grinding the plant (powder form), dissolving in methanol 800 ml, leaving it overnight, filtration with filter paper, then collecting the filtrate, and adding equal volumes of iron solution in a beaker. We observed color change due to nanoparticle formation. By using UV - visible spectroscopy, we proved the presence of nanoparticles manufactured using pomegranate. After that, we studied its antibacterial effect by using several concentrations to determine the least effective (MIC) concentration against the bacteria Staphylococcus aureus on Mueler Hinton agar media.

Results (if a Case Study enter NA)

The nanoparticles were formed strongly and remarkably, and the color quickly changed to an intense black color, even before using the magnetic mixer. The UV - visible spectroscopy characterizes the synthesized Fe3O4 (MNPs). The peak was at 410 nm, and the black color was developed to indicate the presence of (MNPs). Then we performed antibiotic testing on Staphylococcus aureus by using several concentrations. The nanoparticles were highly effective by using the full concentration and effective by using 1/2, 1/4, 1/8 concentrations. But it was inactive when the concentration was 1/16.

Conclusion

Nanotechnology is a modern technique to perform an accurate and reliable method for diagnosing and treating many diseases. The magnetic nanoparticles coated with the active ingredients of pomegranate extract facilitate its use the use of them as an antibacterial agent.
Assessing the Efficacy of a Modified Triple Drug Regimen Supplemented with Mastic Gum in the Eradication of Helicobacter pylori Infection
Authors: Addissouky T A , Khalil A A , El Agroudy A E
Published: November 2023

Introduction/Objective

Helicobacter pylori (H. pylori) is a bacterium that infects the stomach and small intestine. It is known to be the main cause of gastritis and peptic ulcers. The infection is common worldwide, with a prevalence rate of 50% in many countries. Eradication of H. pylori infection is crucial, as failure to do so can lead to serious complications such as gastric cancer. Treatment for H. pylori infection involves a combination of antibiotics, proton pump inhibitors (PPIs), and bismuth compounds. However, due to the emergence of antibiotic resistance, there is a need for alternative treatments.

Methods/Case Report

This study had been a randomized controlled trial involving 180 patients with H. pylori infection. The patients had been divided into two groups: Group A received the standard triple-drug regimen (clarithromycin, amoxicillin, and omeprazole), while Group B received the triple-drug regimen along with mastic gum. The treatment duration was 14 days for both groups. Baseline demographics and clinical characteristics had been collected for all patients. The presence of H. pylori infection had been confirmed by a urea breath test and fecal antigen test.

Results (if a Case Study enter NA)

This study has investigated the effects of mastic gum on H. pylori infection. In a randomized controlled trial of 180 H. pylori-positive patients, mastic gum was found to be effective in eradicating the bacteria in 83 of 90 patients (92.2%) who received the supplementation Group B received the triple-drug regimen along with mastic gum, compared to only 57 of 90 patients (63.3%) in the group A (p < 0.001). Thus, a randomized controlled trial of 90 patients with H. pylori infection found that combination therapy of mastic gum and a triple-drug regimen resulted in a significantly higher eradication rate (92.2%) compared to a triple-drug regimen only (63.3%).

Conclusion

The current study investigated the adding mastic gum to the standard triple-drug regimen can improve the eradication rate of H. pylori infection. This could potentially offer an alternative treatment option for patients with H. pylori infection, especially those with antibiotic resistance. Applying the mastic gum has approved its effectiveness, and it could reduce the reliance on antibiotics and minimize the risk of resistance development.
Metastatic micropapillary cervical adenocarcinoma presenting as a cystic neck mass: a diagnostic pitfall that can be mistaken with metastatic papillary thyroid carcinoma
Authors: Samiei A , Mesa H , Segura S , Cramer H M
Published: November 2023

Introduction/Objective

Micropapillary endocervical adenocarcinoma is a rare aggressive variant of cervical adenocarcinoma with a high propensity for lymphovascular spread and poor outcomes. A 69-year-old woman presented with bilateral neck masses for 6 months. Imaging showed multiple multilocular cystic lateral neck masses. Fine needle aspiration was non-diagnostic. A core biopsy showed a papillary adenocarcinoma positive for TTF-1, Napsin-A, and PAX-8 immunostains, and negative for thyroglobulin, interpreted as metastatic papillary carcinoma of possible lung or thyroid origin. Further imaging of the head, neck, and thorax did not reveal a clear primary, but there was extensive involvement of the neck and mediastinal lymph nodes. Given the disease distribution and prominent cystic change in the nodal metastases, the patient underwent total thyroidectomy, bilateral neck, and mediastinal dissections for a presumed thyroid primary. No tumor was found in the thyroid gland. On follow-up the patient was noted to have normal serum thyroglobulin and retroperitoneal lymphadenopathy on PET/CT scan, prompting the search for a pelvic source. Additional immunostains performed in existing samples showed strong estrogen and progesterone receptor expression suggesting a gynecologic primary. At reevaluation, it was found that the patient had postmenopausal bleeding for a year. The colposcopy examination was normal, but a pap smear showed adenocarcinoma. An endocervical biopsy confirmed a micropapillary variant of endocervical adenocarcinoma.

Methods/Case Report

case report

Results (if a Case Study enter NA)

NA

Conclusion

Micropapillary carcinomas occur at multiple sites and are associated with the prominent lymphovascular spread and poor outcomes. The association of prominent neck and mediastinal lymphadenopathy, papillary architecture, cystic metastases, and coexpression of TTF-1, Napsin-A, and PAX-8 led to an erroneous presumption of a thyroid primary. This case highlights how overlapping immunomorphological features between thyroid and gynecologic tumors with papillary architecture, anchoring and confirmation biases, and suboptimal anamnesis can lead to an erroneous diagnosis.
Acalabrutinib-Related Dermal Toxicities: A Next-Generation Diagnostic Challenge
Authors: Platero Portillo T M , Dhaliwal D , Krishnan B
Published: November 2023

Introduction/Objective

Bruton's tyrosine kinase (BTK) inhibitors represent an advance in treating multiple hematologic malignancies. Next-generation BTK inhibitors, acalabrutinib, have been designed to optimize BTK inhibition and decrease the potential of associated side effects.

Methods/Case Report

A 74-year-old male presented with generalized weakness and shortness of breath. Radiological examination revealed bilateral pleural effusions, lymphadenopathy, and hepatosplenomegaly. Evaluation of the pleural fluid showed a low-grade lymphoma. A lymph node and bone marrow biopsy revealed B-cell lymphoma with lymphoplasmacytic differentiation, with bone marrow involvement. MYD 88 mutation was identified, and it was consistent with Waldenstrom's macroglobulinemia. Acalabrutinib therapy was started, with good response. Two weeks later, he presented with two distinct rashes. 1)Blanching erythematous macules and papules coalescing to patches on the upper thighs and hypogastric region. Punch biopsy of this rash showed superficial perivascular dermatitis with predominantly T-cells and mild lobular panniculitis consistent with BTK inhibitor toxicity. 2)Red-brown erythematous plaques with induration on the central chest. The biopsy of this rash showed cutaneous involvement by the known B- cell lymphoplasmacytic lymphoma.

Results (if a Case Study enter NA)

NA

Conclusion

Cutaneous involvement by Waldenstrom Macroglobulinemia is uncommon. It can be due to 1) nonspecific rashes secondary to the hyperviscosity or cryoglobulinemia 2) cutaneous involvement by the lymphoma, called cutaneous macroglobulinosis.

We present uncommon simultaneous cutaneous involvement of Waldenstrom’s Macroglobulinemia and BTK inhibitor toxicity. BTK-inhibitors-induced rashes present with a relatively non-specific and varied clinical presentation, often in chronically ill patients taking additional medications. Next-generation BTK inhibitors present a more selective binding to BTK. However, they are still associated with similar dermatological toxicities. A high index of suspicion is needed for diagnosis and treatment.
HIV Associated Kaposi’s Sarcoma with Visceral Involvement and Rectal Bleeding
Authors: Salehiazar S , Mirzaei Baboli K , Salahi W , Qing X
Published: November 2023

Introduction/Objective

Kaposi’s sarcoma (KS) is one of the complications of advanced HIV disease and human herpes virus 8 (HHV-8) is the etiological agent. Most cases of KS are cutaneous and resolved with HIV treatment, few cases of KS present with visceral involvement and have a poor prognosis. Any part of the gastrointestinal tract (GIT) may be affected by KS, however visceral involvement without cutaneous lesions is extremely rare. KS has metastatic potential and can be fatal if treatment is not initiated immediately.

Methods/Case Report

A 29 years old homosexual man with a history of multiple sexually transmitted diseases and HIV infection (CD4: 331 cell/μL, CD4/CD8: 0.2, HIV RNA: 10542 copies/mL) presented to the emergency department in a hypovolemic state with hemoglobin of 6 g/dl. He received HAART 3 years ago but discontinued it due to the COVID pandemic. He had a history of recurrent and intermittent rectal bleeding which was exacerbated during the past 3 months. On physical examination, a bleeding rectal mass and bilateral inguinal adenopathy were noted. An imaging study was performed and showed a 14 cm anorectal mass extruding through the anal canal, with bilateral axillary, inguinal, pelvic side walls, iliac chains, and periaortic lymphadenopathy. Flow cytometry of the fresh biopsy tissue revealed a T cell-predominant lymphoid population with reversed CD4/CD8 ratio, compatible with the patient's known history of HIV, with no immunophenotypic evidence of lymphoma. Histopathologic examination of an excisional biopsy of the rectal mass showed mild to moderate atypical spindle cells arranged in vague fascicles and separated by slit-like vessels and extravasated red blood cells. Immunohistochemical (IHC) stain revealed the atypical spindle cells were positive for HHV-8, CD31, CD34, D2-40, BCL2, Vimentin, and Ki-67 (35%-highly proliferative) whereas these cells were negative for AE1/AE3, CK5/6, P40, CD45, Desmin, and S100. A diagnosis of KS was made.

Results (if a Case Study enter NA)

NA

Conclusion

We present a case of visceral KS without cutaneous involvement, which may pose a difficulty in diagnosis. The GIT, lungs, and lymph nodes are the relatively common sites that are affected by visceral KS. KS manifests various histopathological and clinical pictures, and a delay in diagnosis can cause a worse prognosis. The treatment options for KS are depending on the clinical presentation and the extension of the lesions. A combination of HAART, chemotherapy, and radiotherapy could be an effective treatment in the early stage of the disease.
Carcinoembryonic antigen (CEA) expression in human tumors: A tissue microarray study on 15,413 tumors
Authors: Jansen K , Kornfeld L , Lennartz M , Blessin N C , Dwertmann Rico S , Kind S , Büscheck F , Menz A , Sauter G , Simon R , Bernreuther C
Published: November 2023

Introduction/Objective

Carcinoembryonic antigen (CEA; CEACAM5) is a cell surface glycoprotein which constitutes an attractive therapeutic target and serum CEA is used for cancer monitoring. CEA is overexpressed in various cancers, but the reported prevalence data vary considerably for many tumor types.

Methods/Case Report

To comprehensively determine CEA expression in normal and neoplastic tissues, a tissue microarray containing 15,413 samples from 120 different tumor types and subtypes as well as 76 different normal tissue types were analyzed by immunohistochemistry.

Results (if a Case Study enter NA)

CEA positivity occurred in 65 of 120 tumor categories including 49 entities with at least one strongly positive case. CEA positivity was most common in colorectal carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1%-80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), squamous cell carcinomas of various sites (30.2%-69.1%), and small cell carcinomas of the lung (64.3%), the urinary bladder (38.9%), and the prostate (50.0%). High CEA expression was linked to high grade (p<0.0001) and invasive growth (p<0.0001) in urothelial carcinoma. Reduced CEA expression was associated with mismatch repair deficiency (p<0.0001) but not with pT and pN stage in colorectal cancer.

Conclusion

In summary, CEA is abundantly expressed in a broad range of epithelial neoplasms. Our data thus identify various tumor entities where CEA positive cancers might best benefit from CEA serum monitoring and anti- CEA therapies.
GAD2 is a highly specific marker for neuroendocrine neoplasms of the pancreas
Authors: Lennartz M , Dünnebier N B , Blessin N C , Höflmayer D , Dwertmann Rico S , Kind S , Büscheck F , Sauter G , Simon R , Minner S , Bernreuther C
Published: November 2023

Introduction/Objective

Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin-producing β-cells of pancreatic islets. The limitation of GAD2 expression to normal brain and pancreatic islet cells makes GAD2 a potential immunohistochemical diagnostic marker.

Methods/Case Report

To evaluate the diagnostic utility of GAD2 immunohistochemistry (IHC), a tissue microarray containing 19,202 samples from 152 different tumor entities and 608 samples of 76 different normal tissue types was analyzed. Data on progesterone receptor (PR) expression were available on 15,232 tumors from a previous study.

Results (if a Case Study enter NA)

GAD2 positivity occurred in 20 of 152 tumor categories including 5 tumor categories with at least one strongly positive case. GAD2 positivity was most frequent in neuroendocrine carcinomas (58.3%) and neuroendocrine tumors (63.2%) of the pancreas, followed by granular cell tumors (37.0%) and neuroendocrine tumors of the lung (11.1%). GAD2 in <10% of cases occurred in 16 other tumor entities including paraganglioma, medullary thyroid carcinoma, and small cell carcinoma of the urinary bladder. In a cohort of 95 pancreatic and 380 extra-pancreatic neuroendocrine neoplasms, GAD2 had a sensitivity of 64.2% and a specificity 96.3% for pancreatic tumor origin while PR had a sensitivity of 56.8% and a specificity of 92.6%.

Conclusion

GAD2 IHC is a highly useful diagnostic tool for the identification of pancreatic origin in case of neuroendocrine neoplasms with unknown site of origin. The particular strength of GAD2 is its high specificity for pancreatic origin. For the distinction of a pancreatic tumor origin, both sensitivity and specificity is higher for GAD2 than for PR. The combination of PR and GAD2 further increases sensitivity and specificity.
Mucocele of the Anorectal Pouch: Mucinous Cystic Neoplasm with Low-Grade Dysplasia Simulating Low- Grade Appendiceal Mucinous Neoplasm (LAMN)
Authors: Aydin H B , Faraz M , Qiu H , Lee H , Chismark A D
Published: November 2023

Introduction/Objective

We present the second case of colonic mucocele with dysplasia. To date, only five cases of colonic mucocele have been reported, all in the setting of a pouch or bypass, with only one of them showing dysplasia. The exceptional rarity of the lesion provides unique insight into etiology of mucocele.

Methods/Case Report

A 44-year-old male with complex surgical history including pull-through procedure for imperforate anus at birth, and later proctectomy with end colostomy due to poor anorectal function, presented with worsening low back pain radiating down to his left leg. An abdominal CT scan revealed a large pelvic cyst, causing compressive neuropathy. Multilocular cystic mass (17.5 cm) was resected, which was partially filled with mucinous material. Mucin was not seen on the cyst surface. On microscopic examination, the cyst was largely denuded however was partially lined by markedly attenuated ano-rectal type mucosa and focally by dysplastic glandular epithelium.

Similar to LAMN, pools of acellular mucin dissecting stromal tissues were noted, associated with degenerative changes, calcifications and fibrosis. No invasive carcinoma or high-grade dysplasia was seen. Given the lack of extra- cystic mucin or evidence of overt malignancy, it was reported as mucinous cystic neoplasm with uncertain malignant potential. The patient has been followed for 16 months without evidence of recurrence or peritoneal disease.

Results (if a Case Study enter NA)

NA

Conclusion

Extended stasis within a bowel segment appear to contribute to the development of mucoceles. The blind-ended anatomy of the appendix renders it highly susceptible to this phenomenon, explaining the relatively high incidence of LAMN. Conversely, such prolonged stasis rarely occurs elsewhere in colon unless a pouch or bypassed segment is surgically created, particularly placing patients with a complex surgical history at the highest risk.

Therefore, close follow-up is indicated in this patient group to screen for mucocele that may progress to develop dysplasia and mucinous neoplasm.
Histologic findings in Ogilvie’s syndrome
Authors: Usman A , Sami F I , Lack M , Hamza A
Published: November 2023

Introduction/Objective

Ogilvie Syndrome also known as acute colonic pseudo-obstruction is a rare condition characterized by massive dilation of the colon in the absence of a mechanical obstruction. Leading risk factors include critically ill or hospitalized patients with electrolyte disturbances, in the setting of surgery or trauma. It can be managed conservatively, but if unrecognized and untreated, can lead to life-threatening complications such as ischemic colitis.

The purpose of this report is to describe a case with this complication and its relevant histopathological findings.

Methods/Case Report

A 79-year-old male who had recently undergone radical cystoprostatectomy for urothelial carcinoma presented with significant abdominal distention and unstable vital signs. CT scan showed severe cecal dilation with pneumatosis and portal venous gas concerning for ischemia and perforation. The patient subsequently underwent total colectomy. Grossly, the segment of colon showed areas of mucosal sloughing with a hyperemic and indurated serosal surface.

Microscopically, the sections showed surface erosions, acute inflammatory exudate

(pseudomembranes), attenuated crypts, crypt cytoplasmic mucin loss and vascular congestion, compatible with ischemic changes. In the absence of recent major surgery and critical condition pointing towards Ogilvie's syndrome, these findings can elicit the differential diagnosis of infectious colitis, drug-mediated injury, and inflammatory bowel syndrome.

Results (if a Case Study enter NA)

N/A

Conclusion

This case highlights that Ogilvie’s syndrome can histologically manifest as ischemic colitis and emphasizes that in absence of clinical impression of this syndrome a broader differential diagnosis should be entertained.
Coexistence of Low Grade Appendiceal Mucinous Neoplasm and Endometriosis of the Appendix
Authors: Aryal V , Jum'ah H , Loeffler A , Rayes-Danan R
Published: November 2023

Introduction/Objective

Mucinous neoplasms of the appendix are rare malignancies, and most are found incidentally during surgery and subsequently diagnosed upon pathological examination. The prevalence is about 0.2-0.7%, and approximately one-third (3-34%) are low-grade mucinous neoplasms (LAMNs). Endometriosis is relatively rare in the appendix, accounting for 2.8% with prior history of endometriosis and 0.3% found incidentally in resected specimens. Rare cases of LAMN co-existing with endometriosis have been described in the literature. We report this case of a childbearing age female with the coexistence of LAMN and endometriosis with scarring of the appendix found intraoperatively during the laparoscopic removal of the endometriosis.

Methods/Case Report

A female of childbearing age presents to the hospital with complaints of heavy menses, dysmenorrhea, dyspareunia, and dyschezia during menstruation. The patient has a past medical history of endometriosis. With unsuccessful conservative treatment, the patient was advised to undergo laparoscopic excision of endometriosis. Incidental intraoperative sclerotic small appendix and fibrotic surrounding area was identified, leading to the suspicion of appendicitis likely due to previous recurrent episodes of endometriosis. The surgery was then extended to laparoscopic appendectomy. Histologically, the sections from the appendix showed areas of endometriosis surrounded by endometrial stroma (CD10 positive), also there was atypical glands in the muscularis layer with extra-appendiceal mucin. The glands were lined by cells with elongated nuclei, apical mucin and low-grade nuclear atypia. The patient was diagnosed with low-grade appendiceal neoplasm, extending to the mesoappendix with endometriosis.

Results (if a Case Study enter NA)

N/A

Conclusion

The coexistence of the LAMN and endometriosis is a rare entity. Intestinal metaplasia has been reported in some cases of endometriosis, and this may mimic LAMN. It is important to keep intestinal metaplasia of endometriosis in mind when diagnosing LAMN in an appendix with endometriosis. In our case, the presence of dysplasia, the absence of extensive decidualization, the extracellular mucin helped with the diagnosis.
Uterine Inflammatory Myofibroblastic Tumor with ALK Polysomy: Challenging Case Report and Review of Literature
Authors: Belogrivtseva Y , Yin J , Hennawy R , Taraif S
Published: November 2023

Introduction/Objective

Inflammatory myofibroblastic tumor (IMT) is a distinct neoplastic process with specific molecular alterations. Given its low likelihood of local recurrence and metastasis, it is currently regarded as a neoplasm with intermediate biological potential. IMTs of the uterus variably express CD10 and smooth muscle markers, which present a diagnostic challenge and make it difficult to distinguish from mesenchymal neoplasms of smooth muscle and endometrial stromal origin.

Methods/Case Report

We present a case of a 46-year-old woman who underwent a hysterectomy due to abnormal menstrual bleeding. Grossly, a 5.0 cm tan, firm, well-circumscribed subendometrial nodule was identified at the fundus, which had a fleshy, soft-cut surface with no hemorrhage or necrosis. Microscopically, the nodule is composed of somewhat tightly packed spindle cells arranged in a fascicular pattern, with little-to-no myxoid stroma and dense lymphoplasmacytic infiltrate forming scattered aggregates. Immunohistochemical stains show lesional spindle cells are positive for SMA, desmin, and vimentin with patchy staining for ER while negative for S100, CD10, ALK-1, STAT6, and CD34. CD68 highlights scattered histiocytes in the background. Ki-67 highlights background lymphoid cells. RNA next-generation sequencing detected no fusions involving ROS1, PDGFR-β, or ETV6, which were previously described in a subset of ALK-negative IMTs. The FISH assay did not reveal rearrangements of the ALK or ROS1.

However, extra intact ALK fusion signals were observed, suggesting polysomy for the ALK region.

Results (if a Case Study enter NA)

NA

Conclusion

To our knowledge, this is the first report of a uterine IMT with ALK polysomy. The significance of additional ALK copies in our case is not clear but highlights the need for further molecular studies investigating genetic alterations in ALK-negative IMTs. Detecting these rearrangements may be of diagnostic value and help guide future targeted therapies.
DICER1-Mutant Thyroid Carcinoma of Unusual Morphology: A Follicular Carcinoma with Bizarre Nuclei or a Novel Entity?
Authors: Monroe H , El Naili R
Published: November 2023

Introduction/Objective

DICER1 mutations are associated with a host of benign and malignant neoplasms, of which the thyroid ranks among those with the highest prevalence. We present a case of a DICER1-mutant thyroid carcinoma with unusual morphologic features not described in the existing literature.

Methods/Case Report

A 29-year old 33 weeks pregnant female presented with swelling of the left neck. The patient subsequently underwent an ultrasound, which revealed a thyroid lesion measuring 6.2cm in greatest dimension. Labs including TSH and free T4 wree within normal 3rd trimester limits. Following an unremarkable delivery, FNA revealed loosely clustered cells with marked hyperchromasia and nuclear pleomorphism and variable microfollicular architecture in a colloid-containing background. Though definitively malignant, the anomalous cytomorphology of this neoplasm prompted molecular testing by Afirma Genomic Sequencing Classifier and Xpression Atlas next-generation sequencing, which was significant for a DICER1 hotspot mutation (p.E1705K c.5113G>A).

Follow-up total thyroidectomy was pertinent for a tan-red, nodular mass involving 95% of the thyroid. Histomorphology revealed a neoplasm of primarily macrofollicular architecture with scattered microfollicles and intervening zones that appeared poorly-to-undifferentiated. Cells demonstrated bizarre hyperchromatic, pleomorphic nuclei with multinucleation and Azzopardi effect. Capsular invasion was identified. Inconsistent with a poorly-differentiated or anaplastic carcinoma, the mitotic rate and Ki-67 index were low at < 1/2mm2 and 1-2%, respectively. The tumor was consequently theorized to represent a follicular carcinoma with bizarre nuclei or other entity associated with DICER1 mutations not previously described. To date, no recurrence or metastasis has occurred.

Results (if a Case Study enter NA)

NA

Conclusion

We report an enigmatic morphology of a thyroid cancer associated with a DICER1 mutation. DICER1 mutations have been hitherto described in follicular carcinoma, papillary carcinoma, poorly-differentiated carcinoma and thyroblastoma, none of which are consistent with the present case. Thus, we conjecture that this morphomolecular profile may constitute a "follicular carcinoma with bizarre nuclei" or other novel entity not previously reported. Further investigation should be pursued to determine the nature of this entity, its pathophysiology, epidemiology, possible association with germline DICER1 syndrome, and relationship between morphology and prognosis in patients with DICER1 mutations.
Adenoid Ameloblastoma- A very rare, odontogenic tumor variant with less than 20 reported cases in the literature: Report of two cases and literature review
Authors: Jabbar M , Amer S , Belogrivtseva Y , Lazim A , Proca D , Kuklani R
Published: November 2023

Introduction/Objective

We describe two cases of Adenoid Ameloblastoma (AA), a very rare, hybrid variant, of two of the most common odontogenic neoplasms (Ameloblastoma and adenomatoid odontogenic tumors). AA is a benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. The lesion tends to recur, and sometimes, only correctly diagnosed after recurrence.

Methods/Case Report

Adenoid Ameloblastomas were identified after a review of the Temple University, Department of Pathology archive from 2012-2022. A total of four specimens (two patients) were identified.

Results (if a Case Study enter NA)

Case# 1 22-years-old female

Biopsy

Location/ size: Mandible, left, 2.1 cm.

Microscopic: Neoplastic proliferation composed of odontogenic epithelium in a plexiform pattern with the formation of pseudo glandular structures of variably sized cystic spaces, the peripheral epithelial cells are palisaded with reversed polarity. The central cells have clear cytoplasm and resemble stellate reticulum with occasional tight whorls of cells noted. Hemorrhage and giant cells are present in granulation tissue. The lesion was incompletely excised.

Diagnosis: Benign odontogenic tumor.

Case#2 (1st occurrence):

-49-years-old male

-Biopsy

-Location and size of lesion: Maxilla-left anterior, 0.9 cm.

-Microscopic: Cyst lined by loosely arranged epithelial cells with a basal cell layer having hyperchromatic and palisaded nuclei. Knots of squamous cells are present within the cyst lining. The luminal layer is flattened to cuboidal and nonkeratinized. Duct-like openings are present within the epithelium and contain myxoid stromal tissue. Focally the epithelium extends into the connective tissue as thin anastomosing strands surround the myxoid tissue.

-Diagnosis: Benign odontogenic tumor.

Case#2 (2nd occurrence):

-Biopsy

-Diagnosis: Benign odontogenic tumor

Case#2 (3rd occurrence):

-Excisional biopsy

-Diagnosis: AA

Conclusion

AA is a rare, aggressive odontogenic tumor variant with morphologic overlap with other odontogenic lesions; therefore, oral pathologists and clinicians should be familiar with this entity to achieve an accurate diagnosis and prompt management.
Inflammatory pseudotumor of frontal sinus mimicking an aggressive malignancy: a rare case with diagnostic challenge on fine needle aspiration
Authors: Shaheen M , Saeed O A , Hou T
Published: November 2023

Introduction/Objective

Inflammatory pseudotumor (IPT) of sinonasal tract is a rare disease that sometimes mimicks malignancy in radiographic findings. Diagnosis of IPT on fine needle aspiration (FNA) is challenging due to limited cellularity and lack of architectural evaluation.

Methods/Case Report

Patient is a 59-year-old female presented with left front head swelling, facial pain and pressure. Imaging demonstrated a 3.0 cm hypermetabolic frontal sinus mass with osseous erosion through the calvaria table and deviating the adjacent dura, suspicious for malignancy. Also, an incidental 6.8 cm renal mass was identified and was proven to be clear cell renal cell carcinoma. FNA from frontal sinus showed loosely cohesive atypical cells with prominent nucleoli and occasional mitotic activity mixed with lymphoplasmacytic inflammation and eosinophils. Extensive immunostains showed that the lesional cells were only weakly stained for CD10 and desmin. Because of prominent cytologic atypia and radiological concerning for malignancy, FNA was diagnosed as malignancy not further classified. The patient underwent frontal sinus resection and the surgical specimen showed spindle cell proliferation surrounded by reactive woven bone with plump osteoblasts in a myxocollagenous stroma containing mixed lymphoplasmacytic cells and eosinophils. The spindle cells are positive for actin and calponin, negative for ALK. The spindle cells and plump osteoblasts corresponded to the atypical cells observed on FNA. The overall finding is consistent with IPT, although inflammatory myofibroblastic tumor cannot be completely ruled out. During follow up, the patient developed metastatic renal cell carcinoma in lung. Her frontal sinus lesion was stable for 17 months after surgery.

Results (if a Case Study enter NA)

NA

Conclusion

IPT of sinonasal tract is a rare lesion that sometimes demonstrate aggressive radiologic features. FNA from IPT poses a diagnostic challenge and can be misinterpreted as malignancy due to prominent cytologic atypia. Being aware of this rare entity helps avoid misdiagnosis and triggers the request for core biopsy during onsite evaluation.
Not all hematological malignancies in the gastrointestinal tract are lymphoma
Authors: Cortes P , Patel R , Freeman J
Published: November 2023

Introduction/Objective

Myeloid sarcoma (MS) is a rare entity that may develop in patients with acute myeloid leukemia (AML). Presentation of MS in the gastrointestinal (GI) tract is uncommon. We describe two cases of MS involving unusual sites: the stomach and appendix.

Methods/Case Report

A 64-year-old female consulted for fatigue and abdominal pain. A CT scan of abdomen/pelvis revealed appendicitis and CBC showed 76% blasts. An appendectomy was performed. Histologic examination demonstrated the appendiceal wall infiltrated by malignant cells, ultimately demonstrated to be positive for MPO and weak/variable CD117.

In the second case, a 50-year-old male presented to the emergency department for nausea, vomiting, and elevated amylase. Esophagogastroduodenoscopy with endoscopic ultrasound demonstrated pancreatic inflammatory changes and a subepithelial nodule in the gastric fundus. Biopsy of the nodule revealed gastric epithelium infiltrated by sheets of malignant cells, ultimately demonstrated to be positive for CD34, myeloperoxidase and CD43.

Results (if a Case Study enter NA)

NA

Conclusion

MS is defined as a tumor of myeloid blasts forming outside the bone marrow. Overall, it is an uncommon entity that can occur in patients with known AML, and rarely, as the first sign of AML. Presentation of MS in the GI tract is infrequent (10%), involving primarily the small intestine (63%). The differential diagnosis includes lymphoma, poorly differentiated carcinomas, and melanomas. A review of the clinical history for AML or other myeloproliferative neoplasms should raise suspicion of MS. Expression of lymphoid markers and scant tissue for IHC studies can be diagnostic challenges, rendering B cell lymphoma as the most common misdiagnosis of MS in up to 40-47% of cases. Our two MS cases presented exclusively with GI symptoms without previously known AML and involved unusual GI sites. IHC for myeloid lineage, monocytic or myelomonocytic differentiation should be considered in specific cases. In patients without prior AML diagnosis, especially without hematologic findings, MS is a diagnostic challenge.
EBV positive plasmacytoma in immunocompetent patients: A diagnostically challenging rare entity
Authors: Khan A I , Kataria N , Khan A , Hanan A , Edappallath S , Khattar P , Bedi P
Published: November 2023

Introduction/Objective

Epstein-Barr Virus (EBV)-positive plasmacytoma is a rare entity that shows morphological and immunophenotypic overlap with plasmablastic lymphoma and can cause a diagnostic dilemma. Here we discuss a unique case of EBER-positive plasmacytoma arising from nasal polyps.

Methods/Case Report

A 61-year-old immunocompetent male presented with nasal polyps, right maxillary sinus lesions, and an enlarging sternal lesion. Multiple biopsies were obtained which revealed a diffuse infiltration by atypical plasma cells, that were positive for CD138, MUM1, CD79a, CD56, lambda-in situ hybridization, and Ki67- proliferation index of 20-30%. In situ, hybridization for EBV-encoded viral RNA (EBER) was positive in the neoplastic cells. B- and T- cell markers were negative. The flow cytometry studies detected monotypic lambda-restricted CD38/CD138 positive plasma cells with an aberrant expression of CD56 and CD117. Molecular studies for B-and T- cell gene rearrangement were also negative. A final diagnosis of EBER-positive plasmacytoma was made. The patient was treated with cyclophosphamide, vincristine, doxorubicin, and carboplatin followed by four cycles of RVD, and is doing well.

Results (if a Case Study enter NA)

NA

Conclusion

EBER-positive plasmacytoma poses a diagnostic challenge with plasmablastic lymphoma, specifically in immunocompetent individuals. The useful differentiating clues pointing towards EBER positive plasmacytoma could be a spectrum of morphology ranging from mature to anaplastic, low Ki67 proliferation index, aberrant CD56 and CD117 positivity, and high M- spike on protein studies. Comprehensive clinical, morphologic phenotypic, and genetic investigations are necessary to make a specific diagnosis as the two entities differ in their management.
Epidemiology and Clinical Characteristics of Adult Astrovirus Gastroenteritis in Metropolitan Washington DC, USA: 2016-2023
Authors: Mehdipour Dalivand M , Yee R
Published: November 2023

Introduction/Objective

Astrovirus gastroenteritis is commonly studied in children but not adults. Detection of astrovirus on PCR panels allows for characterization of infected patients. Here, we investigate the epidemiology and clinical characteristics of adult astrovirus infections at our institution.

Methods/Case Report

Stool specimens tested between 01/2016-03/2023 on a gastrointestinal PCR panel (BioFire Diagnostics, Salt Lake City, UT) were analyzed. Chart abstraction was performed to collect patient demographics, laboratory results, clinical presentation and management for patients positive for astrovirus. Fisher Exact Test and 95% Confidence Intervals were calculated where appropriate.

Results (if a Case Study enter NA)

Overall positivity rate of astrovirus was 0.6% (34/5053) with highest (1.02%) in 2018 and none in 2020. The mean age was 32 years old (range:18-52 yo) with majority being Caucasian (56%) and female (56%). Symptoms included diarrhea (100%), abdominal pain (92%), vomiting (47%), and fever (35%).

Comparing patients in age group 30-39 years versus other age groups, vomiting (21% vs 65%, p=0.0173) and fever (40% vs 67%, p=0.717) were less prevalent. More females had abdominal pain (95% vs 87%, p=0.6) while more

males had fever (47% vs 26%, p=0.3) although insignificant. Average period of diarrhea was 3 days (range:1-10 days). 23.5% of patients had increased monocytes (CI 0.29-1.92 x 103/µl), and 29.4% showed decreased lymphocytes (CI 0.29-1.10 x 103/µl). Peak seasons were late winter to spring (February-April). All patients were

immunocompetent except one (HIV+). Gastrointestinal co-infections included toxigenic E. coli (12%), C. difficile (6%), Campylobacter (3%), Norovirus (3%), Salmonella (3%) and Stronglyloides (3%). In all 34 patients, clinicians acknowledged detection of astrovirus and discharged patients without antibiotics.

Conclusion

To our knowledge, this is the first case series on adult astrovirus infections from the D.C. area. We report novel findings about adult astrovirus gastroenteritis that are different from observations in children. PCR can rapidly diagnose viral gastroenteritis and can reduce inappropriate antibiotic administration.
Usefulness of Liquid Biopsy for Veteran Patients with Metastatic Lung Cancer
Authors: Dalal S , Petersen J M , Jhala D , Allbee A
Published: November 2023

Introduction/Objective

The National Comprehensive Cancer Network (NCCN) non-small cell lung cancer (NSCLC) Guidelines Panel strongly advises the use of broad molecular tumor profiling to identify rare driver mutations in patients with advanced or metastatic disease. This testing could either be performed on the tumor sample itself or from liquid biopsy with next generation sequencing. Liquid biopsy presents a minimally invasive opportunity to obtain molecular information from circulating tumor cells (CTC) that may impact treatment. However, the literature of metastatic lung cancers targeted by liquid biopsies and the mutations found is sparse, particularly for the veteran population.

Methods/Case Report

A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a Veteran Affairs Medical Center (VAMC) from November 26th, 2019, to March 3rd, 2023, to exa mine those

patients with metastatic lung cancer. Information on mutations detected was collected.

Results (if a Case Study enter NA)

There were a total of 35 patient specimens with a history of metastatic lung cancer, from which 34 cases had an available liquid biopsy report. The first liquid biopsy for a patient with metastatic lung cancer was sent on November 26th, 2019. Some of the more common mutations identified through the liquid biopsy included KRAS (7/34), TP53 (15/34), and TERT promoter (3/34). 5 of these 34 cases had no reportable genomic alterations detected.

Conclusion

Liquid biopsies are a non-invasive, powerful diagnostic tool that is highly useful for broad molecular tumor profiling for precise management and for appropriate counseling of patients on treatment as per the standard of care clinical practice guidelines (such as from the NCCN).
Malignant Melanoma with Atypical Phenotype and RAC1 Mutation
Authors: Vail E , Gayhart M , Azimpouran M
Published: November 2023

Introduction/Objective

Melanoma, a highly invasive form of skin cancer associated with high mortality rates, poses significant challenges in diagnosis and treatment. RAC1, a member of the RHO family of GTPases, plays a crucial role as a molecular switch in cellular processes. A specific mutation in RAC1, caused by C > T transition induced by UV radiation, leads to P29S alteration, activating the SRF/MRTF pathway and triggering a phenotypic switch towards a mesenchymal phenotype.

Methods/Case Report

We present a case of a 74-year-old male patient who presented with a six-week history of right neck swelling. Ultrasonography revealed an enlarged lymph node in the right posterior triangle of the neck. PET scan showed a well- defined, moderately metabolically active lesion measuring 1.4x1.7cm. Initial biopsy indicated a diagnosis of malignant metastatic sarcomatous neoplasm. To establish a definitive diagnosis and determine the appropriate treatment plan, excision of the lymph node was performed. Histological examination revealed lymph node involvement by large, highly atypical cells exhibiting prominent nucleoli and frequent mitotic figures. Immunohistochemical analysis demonstrated positive staining for SOX10 and S100, while Melan-A and HMB45 were negative. Epithelial markers were also negative, although focal keratin positivity was observed. Further investigations were conducted to identify a primary or extranodal site. Routine dermatology visits had previously shown no evidence of primary cutaneous melanoma.

Results (if a Case Study enter NA)

Genomic profiling through next-generation sequencing (NGS) identified multiple alterations, including BRAF (G469R- exon 11, missense alteration), TP53 (R248W, missense alteration in TP53), RAC1 (P29S, missense alteration), TERT (Promoter Site Variant; chr5:g.1295228G>A c.-124C>T), and NF1 (Q1815, nonsense alteration). The tumor exhibited a high tumor mutational burden (TMB) and an ultraviolet (UV) signature characterized by C > T transitions.

Conclusion

Diagnosing melanoma with RAC1 mutation poses significant challenges due to its potential to induce phenotypic switching. Understanding the role of RAC1 mutations in driving melanoma progression can help improve diagnostic accuracy and guide targeted therapeutic strategies.