Search

Myoepithelial tumors are rare neoplasms that develop from myoepithelial cells in glandular structures and soft tissues. Primary intracranial myoepithelial neoplasms are even rarer with around ten cases reported. On the other hand, adrenocortical carcinoma (ACC) is also uncommon with an annual incidence of 0.7–2 per million and carries a poor prognosis. It is known to have an association with certain familial cancer syndromes. Even in sporadic cases, a significant portion of them had other malignancies before and after diagnosis of ACC. We reported a 34-year-old gentleman who was diagnosed to have ACC without known familial cancer syndrome. After that, he was also found to have right occipital myoepithelioma that was confirmed by excisional biopsy. There was no known association between these two pathologies. This is the first report of coincidence of ACC and intracranial myoepithelioma.

We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.

SummaryWe report a 26-year-old man with 6 years, history of duodenal gastrointestinal stromal tumor (GIST) with liver, peritoneum and lung metastases. He presented with left eye ptosis, diplopia, left facial numbness and a left temporal fossa mass that was confirmed to be GIST with left skull and left orbit metastases. Craniectomy with cranioplasty, tumor excision and decompression were performed. There was an improvement of his visual symptoms and facial numbness. To our knowledge, this is one of the few reports of surgical management of GIST, metastasized to skull and orbit, with good symptomatic relief.

Serrated polyps can arise in a sporadic or familial polyposis setting and predispose to colorectal cancer (CRC). Recently, we have identified RNF43 germline mutation in a family with Serrated Polyposis Syndrome (Yan et al, GUT 2016). The presence of second somatic hit in all serrated polyps examined from members of this family further confirmed the pathogenicity of RNF43 germline mutation. In an attempt to further delineate the global genomic alterations in these serrated polyps, so as to understand the RNF43 driven serrated neoplasia pathway for the development of colorectal cancer, we performed whole exome sequencing (WES) on two sessile serrated adenomas (SSAs) resected from an RNF43 germline mutation carrier, together with the paired blood DNA. Consistent with the results from our previous Sanger sequencing study, WES detected complete inactivation of RNF43 through a 2nd hit somatic mutation, c.461 C>T P154L, or loss of heterozygosity (LOH) in the two SSAs, respectively. We also identified 51 and 58 somatic mutations in the two SSAs, respectively. BRAFV600E mutation was the only shared mutation between the two polyps. Interestingly, each of the SSAs carried a truncating mutation in a histone-methyltransferase gene, either PRDM9 or SETD1B, respectively. Other truncating or deleterious mutations included chromatin modifiers (CHD2, CHD4, TSPYL2) or other genes with methyltransferase activity (TRMT2B, METTL12, METTL14, ECE2). In addition, we found few instances of chromosomal aberration or LOH, apart from a region of LOH at chromosome 17 encompassing RNF43 in one of the SSAs. Overall, we have revealed the genomic landscape of two sessile serrated adenomas resected from a germline RNF43 mutation carrier. The results confirmed somatic RNF43 2nd hit and BRAFV600E mutation as the key events, along with putative roles for histone methyltransferase, as well as other chromatin modifiers. These findings highlight the potentially important role of an altered chromatin in the oncogenic pathway of serrated neoplasia. Citation Format: Helen Hoi Ning Yan, Jeffrey C W Lai, Siu Lun Ho, Anthony K W Chan, Wai Yin Tsui, Annie S Y Chan, Siu Tsan Yuen, Suet Yi Leung. Unraveling the oncogenic pathway of serrated polyposis syndrome driven by RNF43 germline mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1448. doi:10.1158/1538-7445.AM2017-1448

With recent advances in 3D organoid culture techniques, normal epithelial and tumor cells can be directly cultured from clinical specimens in vitro and expanded long-term with a very high success rate. Thus, this constitutes a good platform for various mechanistic functional studies and clinical applications. A previous karyotyping and gene expression profiling study has indicated that organoid culture of normal epithelial cells can be propagated for long periods of time without genomic alterations. However, data on the genomic stability of tumor organoids in long-term culture are not yet available. We have successfully established organoid cultures derived from either primary tumor or lymph node metastasis from 4 gastric cancer patients. For each sample, we performed long-term culture for at least 6 months. DNA was extracted from blood, as well as the early and late passages of these organoids, and submitted for whole-exome sequencing (WES), achieving a mean coverage approaching 50X. Somatic mutations detected in early versus late passage gastric cancer organoids were compared. Furthermore, we examined the organoids for copy number variations based on the coverage and loss of heterozygosity (LOH) information derived from exome sequencing. We detected between 80 to 228 somatic mutations in the 4 early passage organoids, in which over 84-99% of them were retained during long-term culture. We detected 16, 20, 31 and 98 new mutations in the 4 long-term cultures, respectively. The one case with a substantially large number of new mutations (n=98) appeared to have emerged from a subclone of TP53 wild-type cells in a TP53 mutant tumor. Notably, the C>T mutation was the most dominant mutation spectrum in this case, constituting 48%. Despite the presence of frequent long segment LOH and chromosomal aberrations in early passage organoids, indicating the presence of chromosomal instability, these patterns of aberrations were stably maintained in long-term passage. Overall, with the current organoid culture protocol, tumor genomes are mostly stably maintained with the accumulation of only a small number of new mutations. Our results indicate that this is a reliable and stable in vitro cell culture model for various cancer-related and clinical studies. Citation Format: Sarah Siu Kuen Yue, Helen Hoi Ning Yan, Hoi Cheong Siu, Siu Lun Ho, Wai Yin Tsui, Dessy Chan, Annie Shuk Yee Chan, Bernard Chi Hang Lee, Anthony Kin Wang Chan, Suet Yi Leung. Gastric cancer organoid culture shows preserved genomic stability in long-term passage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4378. doi:10.1158/1538-7445.AM2017-4378

Primary cutaneous mucoepidermoid carcinoma (MEC) is a rare disease entity. Only around 20 cases have been reported so far. Herein, we present two cases for better understanding of the condition: A 74-year-old lady with a low-grade primary cutaneous MEC at her right external auditory ear canal was treated with surgical resection and adjuvant radiotherapy. The patient developed recurrence five months later and succumbed. Another 81-year-old lady with a high-grade primary cutaneous MEC carcinoma on her left parietal scalp treated by excisional biopsy remained disease free for 10 years. Their histological slides were discussed in details. Current evidence in the literature was also reviewed and summarized.

published_or_final_version, Springer Open Choice, 21 Feb 2012

Dear Editor, A 58-year-old man presented with bilateral, persistent steroid refractory vitritis in 2005. Repeated vitreous biopsies in 2006 and 2007 were inconclusive. In late 2008, he developed vertigo and a magnetic resonance imaging (MRI) scan showed an intra-axial infratentorial tumor with marked cerebellar edema. Brain biopsy showed diffuse large B cell lymphoma (DLCL). Systemic staging, including lumbar puncture, was negative. He was treated as combined intraocular lymphoma (IOL) and primary brain lymphoma (PBL) with chemotherapy [four courses high-dose methotrexate (MTX), rituximab, vincristine, and procarbazine] followed by whole brain radiotherapy (RT, 40 Gy) [1]. This resulted in clinical and radiological remission. Further treatment was limited by poor performance status and renal impairment. His vision remained impaired due to bilateral grade 3 posterior subcapsular cataract and grade 2 cortical cataract. Right eye phaco-emulsification with implantation of posterior chamber intraocular lens was performed in 2008 with good visual recovery. However, his left eye showed progressively decreased acuity to hand movement. An examination showed keratic precipitates, dense cataract, vitritis, retinal infiltrates, and hemorrhages. An MRI and lumbar puncture remained normal. He was treated as recurrent IOL with intrathecal (IT) MTX and cytosine arabinoside (Ara-C). Subsequent left eye cataract surgery and vitreous biopsy showed small lymphocytes but no malignant cells, but panuveitis persisted despite further anterior sub-Tenon’s triamcinolone acetonide injection. A repeat pars plana vitrectomy was performed in 2009. The histology showed large sized atypical lymphoid cells, but an immunogloubin heavy chain polymerase chain reaction study showed no clonality. In view of likely persistent IOL, additional dose-limiting conformal RT was given to both eyes (1.8 Gy/fr up to 28.2 Gy). Vision in his right eye remained good (0.5), but his left eye deteriorated to no light perception. By 2011, he developed left eye pain, florid vitritis, hypopyon, and glaucoma (40 mmHg, Fig. 1a). The painful blind eye was enucleated (Fig. 1b). The specimen showed abundant CD20 positive lymphoma cells in both chambers of the eye (Fig. 1c, d) with frequent mitotic figures and necrosis. Six months later, radiological and physical examinations showed no evidence of brain or orbital lymphoma (Fig. 1e). Fig. 1 a Left eye hypopyon (arrow) of sedimentation of lymphoma cells. b Gross specimen bisected globe with extensive amorphous white infiltrations representing the hypopyon. c Photomicrograph of anterior chamber with abundant lymphoma cell infiltration (arrows ... The related pathologies of IOL and PBL may occur concurrently or sequentially. Central nervous system (CNS) investigation and therapy are advised for apparent isolated IOL [2, 3]. Meticulous fundal examination is also mandatory for PBL patients [4]. The incidence, time sequence, and interval between the entities vary and may be related to the anatomical location of the PBL lesion [5]. Histologically, both conditions are related and extra-CNS spread is uncommon [4]. The treatment includes high dose systemic and IT MTX, Ara-C, and RT [1, 3, 6]. The long-term visual, neurological, and survival prognosis is usually guarded [4, 6]. Our patient is unique in a number of ways. Although IOL is a well-known ophthalmological masquerade lesion, a 3-year lapse between IOL and PBL without treatment is unusual. In addition, the IOL was exquisitely localized to the globe, evident by its isolated nonresponse to chemotherapy, first in both eyes and eventually only in the left eye [6]. After failing multiple maximal dose therapies, the options for a frail patient become limited [1]. The hypopyon is indicative of fulminant lymphoma in the aqueous chamber [2]. Intraocular chemotherapy injection is invasive and may breach the capsular sealing of the amorphous DLCL. It is unlikely to be effective against refractory DLCL. The role of temozolamide or intraocular rituximab is uncertain [7]. Historically, the first effective treatment of IOL was enucleation (c.f. ocular melanoma and retinoblastoma) [6]. Although relegated to a historical curiosity, IOL enucleation remerged as a novel option in our very unique case with refractory localized cells in a painful blind eye. Disease and symptom control was achieved with minimal morbidity.