Stella Blandamura

p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A molecular and immunohistochemical study with clinicopathologic correlations.

p53 gene mutation and p53 protein accumulation are common in human cancer. However, their clinical significance is controversial and p53 accumulation may not correlate with gene mutation. The current study investigates the occurrence of p53 alterations in esophageal carcinoma, the correlation between the analyses at the gene and protein level, and their prognostic significance.

Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology

OBJECTIVES Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. STUDY DESIGN Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. RESULTS Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). CONCLUSIONS Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.

Aggressive angiomyxoma: a second case of metastasis with patient’s death

Aggressive angiomyxoma is a rare tumor that predominates in the female genital tract. Multiple relapses may occur in adjacent organs and tissues, but metastases have not been reported. We present a case of aggressive angiomyxoma in a young woman with multiple local recurrences that metastasized to the lungs, killing the patient. We document this case and report a similar one, found in the literature, of a postmenopausal woman with pulmonary and mediastinic metastases. These cases may expand the current concepts of potential behavior of aggressive angiomyxoma.

Long-term outcomes of surgical resection of the jaws in cancer patients with bisphosphonate-related osteonecrosis.

Surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is controversial. Current recommendations contraindicate aggressive surgery because its results are unpredictable and may trigger disease progression. In this prospective study, we assessed the effectiveness of surgical resection of the jaws in cancer patients with BRONJ. Between June 2004 and July 2009, 30 cancer patients with refractory BRONJ underwent surgical resection of the jaws at our Units. They were followed-up weekly for the first month, at 3-month intervals up to 1 year, and at 6-month intervals up to 2 years. Panoramic radiographs and CT-scan were obtained at 3, 6, 12, 18 and 24 months. Primary outcomes were the 24-month recurrence rate of BRONJ and the 24-month mortality rate. Secondary outcomes were post-operative complications, duration of hospital stay after surgery, time to return to oral diet, and degree of oral pain. The 30 patients had a median age of 66 years and were mostly females (80%). Twenty-eight underwent a single resection and two had both jaws resected, for a total of 32 resected jaws. The cumulative recurrence rate of BRONJ in resected jaws 3.1% and 9.4% at 3 and 6 months, respectively. All the jaws with recurrent BRONJ had osteomyelitis at the margins of bone resection. The cumulative incidence of death was 3%, 12% and 16% at 12, 18 and 24 months. Surgical resection of BRONJ was highly effective, with few post-operative complications and were not associated with long-term mortality.

Vascularized fibula flap reconstruction of the mandible in bisphosphonate-related osteonecrosis.

AIMS To point out the feasibility of microsurgical reconstruction of the mandible in patients with bisphosphonate-related osteonecrosis (BRONJ). METHODS Seven patients with extensive mandibular osteonecrosis underwent subtotal mandibulectomy and immediate reconstruction with a free fibula flap. They were six women and one man aged 49-72 years. The mean size of the bone and oral mucosa defects were 18.5 and 22.5 cm(2) respectively. RESULTS The mean time of surgical intervention was 12 h. All flaps survived and the postoperative course was uneventful. Oral feeding was resumed 14 days after surgery in all cases. The donor legs healed without complications. The pathology report confirmed the diagnosis of BRONJ in all patients. Normal bone was detected at the resection margins in six out of seven patients. Patients were followed-up at intervals of 3 months. After a median follow-up time of 23 months, no clinical and radiographic evidence of recurrent BRONJ were detected in six patients. One patient with osteomyelitis at the resection margins had signs of recurrent BRONJ 6 months after surgery. The overall curative rate of the population was 86%. CONCLUSIONS Despite the limited number of patients studied so far, our data show that mandible reconstruction with the fibula flap is feasible and does not influence the natural course of the primary disease in BRONJ-resected patients.

Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease‐free interval after surgery for squamous cell carcinoma of the larynx

Aims : Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down‐regulated in human breast, prostatic, and colonic cancers but apparently up‐regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma.

Three cases of pancreatic serous cystadenoma and endocrine tumour

Aims: To report three cases of serous cystadenoma and endocrine tumour in the same pancreas, to review the literature and to evaluate the clinicopathological features of the tumours. Cases: Three women (71, 57 and 31 years old) were admitted to hospital, two for diseases unrelated to the pancreas and the third for increasing obstructive jaundice in von Hippel-Lindau disease. Preoperative examination showed two distinct lesions in the first patient and only cystic lesions in the other two. Results: Histological examination of the pancreas showed one serous oligocystic adenoma associated with a benign, well-differentiated endocrine tumour, one serous oligocystic adenoma associated with an endocrine microadenoma, and a von Hippel-Lindau-related cystic neoplasm with a well-differentiated endocrine carcinoma. Conclusions: Serous cystadenoma associated with endocrine tumour shows some clinicopathological differences with respect to the two tumours considered separately, and with respect to von Hippel-Lindau-related cases, although there is no convincing evidence at present to justify considering this association as a separate entity.

Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease-free survival.

Marioni G, Marino F, Blandamura S, D’Alessandro E, Giacomelli L, Guzzardo V, Lionello M, de Filippis C & Staffieri A
(2010) Histopathology57, 535–543
Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease‐free survival

Distant muscular (gluteus maximus muscle) metastasis from laryngeal squamous cell carcinoma.

Clinical evidence of non-lymphatic distant metastasis has been reported in ≈10% of cases of head and neck squamous cell carcinoma (HNSCC). The lungs are the commonest site of distant metastasis of HNSCC, followed by the bones, liver and skin. A 65-year-old male underwent supraglottic laryngectomy and left modified neck dissection for a carcinoma of the laryngeal surface of the epiglottis extending to both false cords. Eight months later the patient underwent right radical modified neck dissection for hypodermal metastatic disease involving the underlying (sternocleidomastoid) muscle. Thirty-two months later, surgical excision of a lesion in the right gluteus maximus muscle was performed. Histological study diagnosed a muscular metastasis with the same morphological aspect as the laryngeal carcinoma. The patient showed no evidence of cervical or distant recurrence at follow-up after 13 months. Although skeletal muscles represent ≈50% of total body mass and receive a large proportion of total cardiac output, haematogenous metastases to skeletal muscle are extremely uncommon. Most skeletal muscle metastases are of pulmonary origin. Distant skeletal muscle metastasis from HNSCC is an extremely rare occurrence. Treatment options, depending upon the clinical setting, include observation, radiotherapy, chemotherapy and excision; these approaches rarely alter the patient outcome. The prognosis associated with skeletal muscle metastasis is thought to be poor, consistent with the fact that it generally occurs as a feature of systemic spread.

Bevacizumab-related osteonecrosis of the mandible is a self-limiting disease process.

A female patient with non-small-cell lung cancer presented with a huge area of exposed bone in the mandible following spontaneous teeth loss. She was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates or comorbid conditions was reported. Pain medications and infection control were offered to the patient who was closely followed up. Initial imaging and histology of bone and surrounding mucosa (8 weeks after bevacizumab cessation) confirmed the clinical suspicion of avascular osteonecrosis of the mandible. Subsequent imaging and histology of bone and gingiva (12 weeks after bevacizumab cessation) revealed the initial sequestration of the mandible with a marked expansion of the mucosal vascular network. Spontaneous bone sequestration eventually occurred few months later, followed by stable and painless mucosal coverage of the mandibular bone. The patient remained disease-free up to 3 years of follow-up.