An Incidental Malignant Gastrointestinal Neuroectodermal Tumor of the Stomach: A Rare Case Report and a Literature Review.

Gastrointestinal neuroectodermal tumors (GNETs) are malignant tumors frequently arising within the muscularis propria of the gastrointestinal tract and often extend into the submucosa and subserosa. The stomach is the second most common site of incidence of GNETs after the small intestine. The most important differential of GNET is the clear cell sarcoma-gastrointestinal (CCS-GI). Both share similar morphological as well as molecular features and show S100 positivity; however, the lack of melanocytic differentiation in GNET distinguishes it from CCS-GI. Both typically show rearrangements of the EWSR1 gene, with t(12;22) (q13;q12) EWSR1-ATF1 or t(2;22) (q34;q12) EWSR1-CREB1 fusions. We present a case of a 71-year-old man with an incidentally discovered GNET in the gastric cardia and fundus.

The diagnostic accuracy of intraoperative frozen section biopsy for diagnosis of sentinel lymph node metastasis in breast cancer patients: a meta-analysis.

Sentinel lymph node (SLN) sampling is important for evaluating the nodal stage of breast cancer when the axillary nodes are clinically free of metastasis. The intraoperative frozen section (IFS) of SLN is used for lymph node assessment. This meta-analysis aims to provide evidence about the diagnostic accuracy and the applicability of IFS of SLN in breast cancer patients. Data were collected by searching PubMed, Cochrane, Scopus, and Web of Science electronic databases for trials matching our eligibility criteria. The statistical analysis included the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and pooled studies' diagnostic odds ratio outcomes. The analyses were conducted using the Open Meta-analyst software. This meta-analysis pooled the results of 110 studies. The overall sensitivity of IFS for SLN metastasis was 74.7%; 95% CI [72.0, 77.2], P < 0.001. It was 31.4% 95% CI [25.2, 38.3], P < 0.001 for the micro-metastasis, and 90.2%; 95% CI [86.5, 93.0], P < 0.001 for the macro-metastasis. The overall specificity was 99.4%; 95% CI [99.2, 99.6], P < 0.001. The overall positive likelihood ratio was 121.4; 95% CI [87.9, 167.6], P < 0.001, and the overall negative likelihood ratio was 0.226; 95% CI [0.186, 0.274], P < 0.001. The overall diagnostic odds ratio of IFS for diagnosing SLN metastasis was 569.5; 95% CI [404.2, 802.4], P < 0.001. The intraoperative frozen section of SLN has good sensitivity for diagnosing breast cancer macro-metastasis. However, the sensitivity is low for micro-metastasis. The specificity is very satisfactory.

A Rare Case of Granular Cell Tumor in the Right Upper Lung of an Adolescent Patient.

Granular cell tumors (GCTs) are rare neoplasms of neuroectodermal origin characterized by large polygonal cells with abundant eosinophilic and granular cytoplasm. GCTs rarely affect the lungs, with only a few cases reported in the literature. The pathophysiology of this Schwann cell-derived condition is not well understood but is thought to be due to recurring genetic mutations. GCTs have been linked with Noonan syndrome. Here, we report the case of a 17-year-old caucasian male who presented with partial upper airway obstruction due to a GCT. This case promotes awareness among pathologists and clinicians for this condition in the workup of patients presenting with upper airway obstruction.

A Rare Case of Sarcoidosis Involving Male Breast Tissue.

Sarcoidosis is a multisystem, inflammatory granulomatous disease that rarely involves breast tissue. The pathophysiology of this chronic granulomatous condition is not well understood but is thought to be multifactorial, involving environmental influences causing an amplified immune response. A key histomorphology feature in sarcoidosis is the presence of non-necrotizing granulomas. In this case, we report a 41-year-old African-American man with a known history of sarcoidosis of the lung who presented with gynecomastia and bilateral breast tenderness with palpable nodules. Subsequent biopsy and microscopic examination of the breast nodules revealed diffuse involvement with non-necrotizing granulomas in both breasts. A final diagnosis of extensive sarcoidosis involving breast tissue was rendered after excluding other causes of non-necrotizing granulomas. The patient underwent a bilateral mastectomy to remove the breast nodules. This case discusses sarcoidosis involving an unusual site.

Efficacy and Safety of Pectoral Nerve Block (Pecs) Compared With Control, Paravertebral Block, Erector Spinae Plane Block, and Local Anesthesia in Patients Undergoing Breast Cancer Surgeries: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to compare the safety and efficacy of pectoral nerve block (Pecs) I and II with control or other techniques used during breast cancer surgeries such as local anesthesia, paravertebral block, and erector spinae plane block (ESPB). METHODS: We searched 4 search engines (PubMed, Cochrane Library, Scopus, and Web of Science) for relevant trials, then extracted the data and combined them under random-effect model using Review Manager Software. RESULTS: We found 47 studies, 37 of them were included in our meta-analysis. Regarding intraoperative opioid consumption, compared with control, a significant reduction was detected in Pecs II (standardized mean difference [SMD]=-1.75, 95% confidence interval [CI] [-2.66, -0.85], P=0.0001) and Pecs I combined with serratus plane block (SMD=-0.90, 95% CI [-1.37, -0.44], P=0.0002). Postoperative opioid consumption was significantly lowered in Pecs II (SMD=-2.28, 95% CI [-3.10, -1.46], P<0.00001) compared with control and Pecs II compared with ESPB (SMD=-1.75, 95% CI [-2.53, -0.98], P<0.00001). Furthermore, addition of dexmedetomidine to Pecs II significantly reduced postoperative opioid consumption compared with Pecs II alone (SMD=-1.33, 95% CI [-2.28, -0.38], P=0.006). CONCLUSION: Pecs block is a safe and effective analgesic procedure during breast cancer surgeries. It shows lower intra and postoperative opioid consumption than ESPB, and reduces pain compared with control, paravertebral block, and local anesthesia, with better effect when combined with dexmedetomidine.

The Rarest of the Rare: A Case of Primary Cardiac Osteosarcoma With a Review of the Literature.

A 54-year-old female presented with shortness of breath and cyanosis. Work up with chest X-ray and subsequent echocardiogram revealed an intracardiac bi-atrial mass leading to emergent cardiothoracic resection. Pathology was consistent with a primary cardiac high-grade osteosarcoma. Post-resection staging positron emission tomography-computed tomography (PET-CT) showed hypermetabolic mixed lytic and sclerotic lesion of T10 concerning for metastasis. She received five cycles of adriamycin and ifosfamide chemotherapy before discontinuation due to systolic dysfunction. Nine months later, she developed a high tumor burden with progressive disease and was treated with second-line gemcitabine/docetaxel with disappointing results. She is currently on treatment with cyclophosphamide and topotecan as third-line treatment with an excellent clinico-radiographic response. Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Fewer than 50 cases of primary cardiac osteosarcomas have been reported in the literature. Even though complete resection can be achieved in some cases, long-term results are usually poor. No standard therapy has been established.

Medullary Carcinoma of the Colon: A Histopathologic Challenge.

Medullary carcinoma (MC) of the colon is a rare and unique histologic subtype of colorectal cancer. It is commonly associated with deficient mismatch repair proteins and has a strong association with Lynch syndrome. Diagnosis is challenging as it does not have the usual immunohistochemical stains on pathology seen in colorectal adenocarcinoma. Here, we discuss an interesting case of MC of the colon that was metastatic on presentation and constituted a diagnostic challenge.

Anti-Lan Antibodies: A Rare Etiology of Severe Blood Transfusion Reaction.

Lan is a high prevalence red blood cell antigen present in the majority of the populations that belong to the Lan (Langereis) blood group system. Anti-Lan antibody is an immunoglobulin G (IgG) antibody that is known to cause delayed hemolytic transfusion reactions in adults as well as hemolytic disease in fetuses and newborns, however with variable clinical significance ranging from mild to severe. We present a 58-year-old woman with diffuse abdominal pain and a large gastric ulcer causing gastric outlet obstruction. She underwent antrectomy and Billroth I reconstruction surgery without complications. The patient's hemoglobin upon presentation was 10g/dL and dropped acutely post-operatively to 6.4 g/dL requiring blood transfusion. The patient developed acute respiratory distress within minutes of starting a packed red blood cell (pRBC) transfusion, requiring discontinuation. Laboratory testing demonstrated pan-reactivity with additional reference testing demonstrating an anti-Lan antibody. The rarity of Lan negative pRBC units is a challenge in managing such patients requiring blood transfusions. Autologous blood donation or donation by a compatible family member is another option to consider in these rare cases.

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients.

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.

Folate receptor alpha expression associates with improved disease-free survival in triple negative breast cancer patients.

Triple negative breast cancer (TNBC) comprises 15-20% of all invasive breast cancer and is associated with a poor prognosis. As therapy options are limited for this subtype, there is a significant need to identify new targeted approaches for TNBC patient management. The expression of the folate receptor alpha (FRα) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FRα immunohistochemistry method, specific to TNBC, to measure FRα expression in a centrally confirmed cohort of 384 patients with TNBC in order to determine if expression of the protein is associated with invasive disease-free survival (IDFS) and overall survival (OS). The FRα IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FRα expression, which varied widely from sample to sample, was detected in 274 (71%) of the TNBC lesions. In a multivariable model adjusted for baseline characteristics, FRα expression was associated with improved IDFS (HR = 0.63, p = 0.01) but not with OS. The results demonstrate the potential of targeting the FRα in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FRα expression in clinical studies.

Long-time Response with Ado-trastuzumab Emtansine in a Recurrent Metastatic Breast Cancer.

Breast cancer is the most common cancer in a woman with a five-year survival of patients with metastatic disease is estimated at 23%. Ado-trastuzumab emtansine (T-DM1) is a HER2-antibody drug conjugate currently approved for the treatment of HER2-positive pre-treated metastatic breast cancer (BC). We report a case of recurrent metastatic breast cancer with unusually lengthy progression-free survival (PFS) on T-DM1 chemotherapy. She was diagnosed with Triple Positive Stage IIIC multifocal invasive ductal carcinoma of the left breast. After completing neoadjuvant chemotherapy, she underwent a bilateral mastectomy. Final pathology showed partial response. Postoperatively, she received adjuvant chemotherapy and radiation therapy. She was started on Q21 days trastuzumab following completion of adjuvant chemotherapy. Systemic imaging showed liver lesions and biopsy confirmed recurrence. She was started on T-DM1, endocrine therapy with anastrozole was continued. She is currently status post 45 cycles. T-DM1 was approved for the treatment (single-agent) of HER2-positive, metastatic BC based on phase III data from the EMILIA and TH3RESA study. Median PFS in the T-DM1 arm was 9.6 months. Herein, we present a case of a woman with recurrent triple positive metastatic BC with a lengthy progression-free survival on T-DM1 chemotherapy.

Downregulation of TAP1 and TAP2 in early stage breast cancer.

TAP1-TAP2 heterodimeric complexes are recognized as the transporter associated with antigen processing of major histocompatibility complex class I peptides for recognition by tumor-specific cytotoxic T lymphocytes. In this study, we investigated the immunohistochemical expression of TAP1 and TAP2 in 160 patients with breast cancer and correlated their expression levels with clinicopathologic parameters. The median age of the patient cohort was 52.5 years (range, 30-86 years). Both TAP1 and TAP2 immunohistochemical expression levels correlated significantly with breast cancer characteristics (P < .001). TAP1 expression levels were low to negative in stage I breast tumors. TAP1 and TAP2 levels were significantly higher in grade 3 tumors than low-grade (grade 1 and 2) tumors. TAP1 and TAP2 expression levels were not significantly different among different levels of HER2-expressing tumors and did not vary by estrogen and progesterone receptor status or patient age. Both TAP1 and TAP2 overexpression in breast cancer might be an indicator of an aggressive breast tumor.