Valerio D'orazi

The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4–74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non‐SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café‐au‐lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14–13.11], which were more frequent in SNF vs MNFSR (p = 0.0271).

Gentian violet induces wtp53 transactivation in cancer cells

Recent studies suggest that gentian violet (GV) may have anticancer activity by inhibiting for instance NADPH oxidases (Nox genes) whose overexpression is linked to tumor progression. Nox1 overexpression has been shown to inhibit transcriptional activity of the oncosuppressor p53, impairing tumor cell response to anticancer drugs. The tumor suppressor p53 is a transcription factor that, upon cellular stress, is activated to induce target genes involved in tumor cell growth inhibition and apoptosis. Thus, its activation is important for efficient tumor eradication. In this study, we examined the effect of GV on wild-type (wt) p53 activity in cancer cells. We found that GV was able to overcome the inhibitory effect of the NADPH oxidase Nox1 on p53 transcriptional activity. For the first time we show that GV was able to directly induce p53/DNA binding and transcriptional activity. In vitro, GV markedly induced cancer cell death and apoptotic marker PARP cleavage in wtp53-carrying cells. GV-induced cell death was partly inhibited in cells deprived of p53, suggesting that the anticancer activity of GV may partly depend on p53 activation. GV is US Food and Drug Administration approved for human use and may, therefore, have therapeutic potential in the management of cancer through p53 activation.

Zn(II)-curc targets p53 in thyroid cancer cells

TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers.

Unexpected granular cell tumor in abdominal wall: Case report and literature review

Granular cell tumors (GCTs) are uncommon benign neoplasms deriving from Schwann cells of the peripheral nerve fibers. Although these tumors can be found anywhere in the body, the most frequent site is the tongue, followed by the chest wall and the arm. The abdominal wall is an extremely rare site for GCTs. These tumors are generally asymptomatic and have a slow growth rate. Today, thanks to their immunoreactivity to S-100 and CD68, the differential diagnosis is more straightforward than in the past. We report on a young patient affected by a GCT located in the upper third of the right rectus abdominis muscle. En bloc excision through a diamond-shaped skin incision allowed us to make a correct histological diagnosis, which was confirmed by the immunohistochemical findings. GCT, which is very rare in abdominal wall muscles, should be considered in the differential diagnosis, and surgical excision is the treatment of choice.

Rare chondrosarcoma of the breast treated with quadrantectomy instead of mastectomy: A case report

Breast chondrosarcoma is a rare sarcoma that mainly occurs in females >50 years old. To the best of our knowledge, only 16 cases were reported in the literature prior to 2013 and all patients were surgically treated by mastectomy, with or without lymphadenectomy, which was occasionally preceded by neoadjuvant chemotherapy. However, the literature does not report the benefit of mastectomy compared with a more conservative surgery. The present study reports a novel case of extraskeletal chondrosarcoma of the breast. A 63-year-old female patient presented with a neoplasm localized in the upper-outer quadrant of the right breast. The palpable lesion with sharp margins was a firm parenchymatous mass, which was confirmed by ultrasonography and mammography. The patient underwent conservative quadrantectomy instead of mastectomy, followed by post-surgical chemotherapy. A positron emission tomography scan performed five months subsequent to the surgery revealed no remnants of the disease. The patient underwent a strict clinical and instrumental follow-up, and two and half years after surgery, there are no signs of recurrent disease. In conclusion, the present case is currently one of the two cases in which a more conservative quadrantectomy was performed, instead of mastectomy. This surgical approach did not lead to metastasis and resulted in a good follow-up for the patient.

Spinal neurofibromatosis with central nervous system involvement in a set of twin girls and a boy: further expansion of the phenotype.

BACKGROUND Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. OBJECTIVES The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. METHODS AND RESULTS In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. CONCLUSIONS This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.

Microsurgical approach for unusual and unexpected malignant fibrous histiocytoma of the forearm: A case report

Soft tissue sarcomas are rare tumors with a dismal prognosis. Among the most common histological types of sarcomas of the extremities, malignant fibrous histiocytoma (MFH) is the one with the highest incidence. Surgery is considered to be the first choice of treatment for MFH. To the best of our knowledge, this is the first case report in the literature of a patient with MFH within the abductor pollicis longus (APL) muscle. This unusual location was also unexpected by the treating surgeons, as the preoperative magnetic resonance imaging localized the tumor inside a different muscle. A 79-year-old Caucasian man presented with a swelling in the middle third of the dorsal aspect of the left forearm. MFH was diagnosed following biopsy and instrumental diagnostic examinations. Surgical excision and simultaneous reconstruction was performed by the same microsurgical team, achieving an excellent functional outcome. The present case highlights the significance of microsurgical approach for improving strategic planning in oncologic surgery. Accurate surgical dissection, performed by a team of microsurgeons, allowed for the identification of the unusual and unexpected tumor localization within the APL muscle. For this reason, a change of surgical strategy allowed for preservation of the extensor digitorum communis muscle, which would otherwise have to be resected, with tendon transfer and successful restoration of the thumb abduction function.

Magnetic resonance imaging after breast oncoplastic surgery: An update

Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncologically safe when applied to early-stage breast cancer. Breast cancer recurrence following conservative therapy may occur during the first 5 years after treatment, with a peak incidence after 2 years. Therefore, during the follow-up period, patients undergo a series of ultrasound (US) and mammographic examinations. However, after surgery and radiation therapy, several modifications occur in the treated breast, causing difficulties in image interpretation, especially when local recurrence is suspected. Although not included in routine follow-up, magnetic resonance imaging (MRI) is often used in clinical practice, being considered more sensitive than the conventional imaging examinations in discriminating between postsurgical tissue modifications and tumor recurrence. In this review article, we analyze expected and pathologic breast MRI findings after conservative oncoplastic surgery compared to US and mammographic findings in order to distinguish local recurrence and avoid potential pitfalls in image interpretation.

Cyst of Canal of Nuck: Our Experience

We report two cases of a cyst of the canal of Nuck in which sonography showed a tubular cystic structure characterized by internal septum localized within the inguinal canal. Unfortunately, Magnetic resonance (MRI) examination was not performed in the first case, however in the second case, MRI demonstrated that the mass suggested an hydrocele of the Canal of Nuck. Both cases were solved satisfactorily and confirmed cysts of canal of Nuck by means of laparoscopic technique.