Thyroglossal Duct Lipoma: A Case Report and a Systematic Review of the Literature for Its Management

Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk’s procedure). For other pathologies associated with the TGD tract, the latter operation might be not necessary. In the present report, a case of a TGD lipoma is presented and a systematic review of the pertinent literature was performed. We present the case of a 57-year-old woman with a pathologically confirmed TGD lipoma who underwent transcervical excision without resecting the hyoid bone. Recurrence was not observed after six months of follow-up. The literature search revealed only one other case of TGD lipoma and controversies are addressed. TGD lipoma is an exceedingly rare entity whose management might avoid hyoid bone excision

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

Predictors of the need for an extracervical approach to intrathoracic goitre

Background: Sternotomy and lateral thoracotomy are required infrequently to remove an intrathoracic goitre (ITG). As few studies have explored the need for an extracervical approach (ECA), the aim of this study was to examine this in a large cohort of patients. Methods: A prospective database of all patients who had surgery for ITG between 2004 and 2016 was interrogated. Patient demographics, preoperative characteristics and type of operation were analysed to identify factors associated with an ECA. Results: Of 237 patients who had surgery for ITG, 29 (12·2 per cent) required an ECA. ITGs below the aortic arch (odds ratio (OR) 10·84; P = 0·004), those with an iceberg shape (OR 59·30; P < 0·001) and revisional surgery (OR 4·83; P = 0·022) were significant preoperative predictors of an ECA. Conclusion: The extent of intrathoracic extension in relation to the aortic arch, iceberg goitre shape and revisional surgery were independent risk factors for ECA. Careful preoperative assessment should take these factors into consideration when determining the optimal surgical approach to ITG

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

Objective: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. Design: Partially retrospective cohort study. Setting: Two Italian transplantation centers. Patients: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. Main Outcome Measures: Cumulative incidences and risk factors of the first and subsequent NMSCs. Results: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a secondNMSCafter a median follow-up after the firstNMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. Conclusions: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both <it>in vivo </it>and <it>in vitro</it>. We found in an <it>in-silico </it>search tight co-regulation between <it>matriptase </it>and <it>claudin-7 </it>expression. We have previously shown that the <it>matriptase </it>expression level decreases during colorectal carcinogenesis. In the present study we investigated whether <it>claudin-7 </it>expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.</p> <p>Methods</p> <p>The mRNA level of <it>claudin-7 </it>(CLDN7) was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings.</p> <p>Results</p> <p>A 2.7-fold reduction in the <it>claudin-7 </it>mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the <it>claudin-7 </it>mRNA levels were also detected in mild/moderate dysplasia (p < 0.001), severe dysplasia (p < 0.01) and carcinomas (p < 0.01), compared to a control sample from the same individual. The decrease at mRNA level was confirmed at the protein level by immunohistochemical stainings.</p> <p>Conclusions</p> <p>Our results show that the <it>claudin-7 </it>mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.</p

Altered regulation of Prox1-gene-expression in liver tumors

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Cutaneous collateral axonal sprouting re-innervates the skin component and restores sensation of denervated Swine osteomyocutaneous alloflaps.

PMC3799840Reconstructive transplantation such as extremity and face transplantation is a viable treatment option for select patients with devastating tissue loss. Sensorimotor recovery is a critical determinant of overall success of such transplants. Although motor function recovery has been extensively studied, mechanisms of sensory re-innervation are not well established. Recent clinical reports of face transplants confirm progressive sensory improvement even in cases where optimal repair of sensory nerves was not achieved. Two forms of sensory nerve regeneration are known. In regenerative sprouting, axonal outgrowth occurs from the transected nerve stump while in collateral sprouting, reinnervation of denervated tissue occurs through growth of uninjured axons into the denervated tissue. The latter mechanism may be more important in settings where transected sensory nerves cannot be re-apposed. In this study, denervated osteomyocutaneous alloflaps (hind- limb transplants) from Major Histocompatibility Complex (MHC)-defined MGH miniature swine were performed to specifically evaluate collateral axonal sprouting for cutaneous sensory re-innervation. The skin component of the flap was externalized and serial skin sections extending from native skin to the grafted flap were biopsied. In order to visualize regenerating axonal structures in the dermis and epidermis, 50 um frozen sections were immunostained against axonal and Schwann cell markers. In all alloflaps, collateral axonal sprouts from adjacent recipient skin extended into the denervated skin component along the dermal-epidermal junction from the periphery towards the center. On day 100 post-transplant, regenerating sprouts reached 0.5 cm into the flap centripetally. Eight months following transplant, epidermal fibers were visualized 1.5 cm from the margin (rate of regeneration 0.06 mm per day). All animals had pinprick sensation in the periphery of the transplanted skin within 3 months post-transplant. Restoration of sensory input through collateral axonal sprouting can revive interaction with the environment; restore defense mechanisms and aid in cortical re-integration of vascularized composite allografts.JH Libraries Open Access Fun

Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution