A Rare Case of Multifocal Asynchronous Benign Granular Cell Tumors with PIK3CA Subclonal Mutation Identified in One Tumor by Next-Generation Sequencing.

Granular cell tumor (GCT) is a benign neuroectodermal tumor typically in the dermis or subcutis, although deep soft tissues and organs are occasionally involved. Multifocal GCTs are estimated to occur as many as 10% of patients. A 40-year-old female presented with multiple GCTs asynchronously involving various body sites including gastrointestinal, gynecologic, breast, urinary, and soft tissue systems. Pathologic examinations suggested benign GCTs. TruSight Tumor 170 next-generation sequencing (NGS) analysis performed on four resected tumors revealed subclonal mutation of PIK3CA p.H1047R identified in the esophageal GCT but not in the right vulva or the two cecal GCTs, suggesting that each is a primary tumor with a distinct genetic profile, rather than metastasis. PIK3CA p.H1047R is a common mutation in many cancers. Our benign GCT case demonstrates PIK3CA mutation with a low mutant allele frequency of 7%, which may represent an evolving subclone and might confer a more aggressive behavior.

Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

BACKGROUND: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce. METHODS: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues. The primary outcome investigated was the association between RRM1 and ERCC1 expression and overall survival (OS) or disease-free survival (DFS). RESULTS: A total of 94 patients with resected PDA were included in this study. Most of them (87%) received gemcitabine based chemotherapy. Data for OS analysis was available in all cases but only 68% had enough information to estimate DFS. IHC analysis revealed information for 99% (93/94) and 100% of the cases for RRM1 and ERCC1 expression respectively. However, PCR data interpretation was possible in only 49 (52%) and 79 (84%) cases respectively. There was no significant association between high or low expression of either RRM1 or ERCC1, detected by IHC and OS (14.4 vs. 19.9 months; P = 0.5 and 17.1 vs. 19.9; P = 0.83 respectively) or PCR and OS (48.0 vs. 24.1 months; P = 0.21 and 22.0 vs. 16.0 months; P = 0.39 respectively). Similar results were obtained for DFS. CONCLUSIONS: RRM1 and ERCC1 expression does not seem to have a clear predictive or prognostic value in pancreatic cancer. Our data raise some questions regarding the real clinical and practical significance of analyzing these molecules as predictors of outcomes.

Platelet refractoriness in acquired hemophagocytic syndrome.

BACKGROUND: Acquired hemophagocytic syndrome (AHPS) is a severe inflammatory disorder often caused by Epstein-Barr virus (EBV). Proliferation of activated macrophages produces uncontrolled cytokine production. Thrombocytopenia is common in AHPS, previously attributed to inadequate or ineffective marrow platelet (PLT) production. PLT transfusion response is not well reported. Two patients with fatal AHPS developed unexplained PLT transfusion refractoriness before definitive diagnosis. CASE REPORTS: PLT refractoriness was noted during the care of two patients. The refractoriness was determined to be nonimmune and both demonstrated various clinical signs and laboratory findings consistent with AHPS. The first patient's AHPS was attributable to EBV infection. In the other patient, no underlying cause could be found. Both patients had an aggressive clinical course and succumbed to this relatively rare syndrome. The PLT refractoriness was evident before the AHPS diagnosis was made. DISCUSSION: AHPS is not generally a consideration in the evaluation of nonimmune PLT refractoriness. However, these illustrative cases make an argument for its consideration in the differential diagnosis of PLT refractoriness in severely ill patients. Once present, it is unclear if the refractoriness can be reversed by AHPS-targeted therapy.

Malignant Phyllodes Tumor in an Adolescent Female: A Rare Case Report and Review of the Literature.

Primary breast neoplasms are rare in adolescent females, most of which are benign. Phyllodes tumors constitute a remarkably small subset of breast neoplasms (0.3-0.9%) with malignant phyllodes tumors being even more uncommon. Malignant phyllodes tumors tend to progress rapidly though only 1.5% metastasize. They are also associated with a higher rate of recurrence than their benign counterparts, underlying the importance of adequate surgical margins. It is therefore imperative to be able to identify these tumors early allowing for prompt resection and close follow-up. Here, we present the rare case of a 17-year-old female presenting with a rapidly enlarging breast mass, which was ultimately found to be a malignant phyllodes tumor. We further performed a review of the literature to highlight only 22 other cases reported in adolescent females.

Squamous cell carcinoma arising in a partially ruptured giant mature cystic teratoma: A case report.

Mature cystic teratomas are the most common ovarian germ cell tumors and represent 70% of the benign ovarian tumors occurring in women under age 30. In less than 2% of cases, these tumors can transform into malignancies. Squamous cell carcinoma arises most frequently from these tumors (in 80% of cases). Intra-peritoneal rupture accounts for approximately 1%-2% of cystic teratoma complications with most ruptures occurring either intraoperatively during laparoscopic surgery or due to trauma. This case report describes the common presentation, imaging, and pathologic findings of a mature cystic teratoma with 2 uncommon associated complications.

Giant Cell Tumor of the Carotid Body: A Rare Tumor in a Novel Location.

Primary giant cell tumor of soft tissue (GCT-ST) is a rare entity that is considered the soft tissue equivalent of giant cell tumor of bone. It most commonly arises in soft tissues of the trunk and extremities, with occurrence in the head and neck being extremely rare. We report a case of GCT-ST of the carotid body, the first report of a tumor of this kind arising from this site in the neck. Giant cell tumor of soft tissue is generally considered a benign tumor with low malignant potential; thus, surgical excision is usually curative. However, due to the location and invasive nature of this patient's tumor, complete excision was not possible. We discuss the implication of this for long-term management of this patient, as well as similarities and differences in clinical presentation, histology, and biological behavior between this case and previously reported cases of GCT-ST.

Recurrent Adolescent Giant-Cell Tumor of the Scaphoid: Scaphoid Excision with Intracarpal Fusion after Failed Curettage and Bone Grafting.

We present a case of the giant-cell tumor of bone in the scaphoid of a 17-year-old female. Imaging revealed an expansile lytic lesion of her scaphoid, and the diagnosis was confirmed with open biopsy. She was treated with curettage and iliac crest bone graft, in an effort to spare reconstruction of her wrist. After one year, she developed increasing tightness and pain. Local recurrence was apparent on radiographs, and CT revealed increased lucency with bony destruction in the area of prior excision. She was successfully treated, without recurrence to date, with complete scaphoid excision and a four-corner wrist fusion. Local recurrence of the giant-cell tumor of bone is high, especially in carpal bones. When treating patients with advanced lesions, more aggressive initial options should be considered.

Large incidental gastrointestinal stromal tumors in a patient presenting with acutely symptomatic nephrolithiasis: A case report.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms, representing approximately 1%-2% of all primary gastrointestinal malignancies. Incidental GISTs are often less than 1 cm when discovered and have been reported predominantly in obese patients undergoing surgery for other medical indications. We present the rare case of a large incidental GIST in a nonobese patient with acutely symptomatic nephrolithiasis. Large GISTs may be treated with neoadjuvant imatinib mesylate to reduce tumor size prior to surgery, though some tumors may experience little change in size despite effective treatment. Treatment response for GISTs can be monitored via imaging studies, such as computed tomography or magnetic resonance imaging, but computed tomography is generally preferred over magnetic resonance imaging.

Ayurvedic drug induced liver injury.

Drug induced liver injury is responsible for 50% of acute liver failure in developed countries. Ayurvedic and homeopathic medicine have been linked to liver injury. This case describes the first documented case of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. Drug induced liver injury may be difficult to diagnosis, but use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging, is recommended. Advanced imaging, such as magnetic resonance cholangiopancreatography, may possibly have a greater role than previously reported in literature.

p16 status, pathologic and clinical characteristics, biomolecular signature, and long-term outcomes in head and neck squamous cell carcinomas of unknown primary.

BACKGROUND: The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP). METHODS: Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC). RESULTS: A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer. CONCLUSION: The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP.