Extramedullary blastic transformation of primary myelofibrosis in the form of disseminated myeloid sarcoma: a case report and review of the literature.

Splenomegaly is a key clinical manifestation of myelofibrosis, and splenectomy is currently indicated in patients with drug refractory, symptomatic splenomegaly or with the aim of improving refractory cytopenias. Transformation to acute myeloid leukemia occurs in up to 20% of patients with myelofibrosis, while cases of myeloid sarcoma have been reported very unfrequently. In this manuscript, we report the case of a 60-year-old man with a history of primary myelofibrosis who underwent splenectomy because of drug-refractory massive splenomegaly, systemic symptoms and anemia. At the opening of the peritoneal cavity, the spleen resulted massively enlarged and tenaciously entrapped by a pervasive neoplastic-like tissue. The extensive involvement of the abdomen fatally complicated the surgical procedure. At postmortem examination, the spleen showed a diffuse infiltration of immature cells that were also found in the peritoneum, bowel, liver, lungs and myocardium. After immunohistochemical, cytogenetic, flow cytometric and molecular characterization of neoplastic population, a diagnosis of disseminated myeloid sarcoma of the spleen was made. This case report highlights a very unusual case of myeloid sarcoma originating from the spleen in a patient with myelofibrosis who had no evidence of bone marrow or peripheral blood involvement by leukemic cells. Molecular characterization showed that leukemic cells originated from the founding clone of the chronic phase. The sarcoma could not be suspected based on clinical findings and was diagnosed only at the time of surgical procedure and autopsy. This case suggests that leukemic transformation of myelofibrosis can originate outside the bone marrow and, presumably rarely, present as a granulocytic sarcoma.

Prognostic importance of sclerosing variant in papillary thyroid carcinoma.

The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma is known for its high aggressiveness, high incidence of lymph node metastases, and high incidence of pulmonary metastases, and thus its consequently poorer prognosis. In this study, we undertook a retrospective analysis of papillary thyroid carcinomas to assess whether DSV can be considered a predictive factor for prognosis. We performed a retrospective evaluation of the Department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1992 to December 2000. Group I consisted of 83 DSV patients and Group II was 168 pure papillary carcinoma (PC) patients. A significant prevalence of multinodular thyroid disorder on diagnosis was found for PC (P < 0.05), whereas with DSV, there was a significantly higher prevalence of post-thyroiditis nodular thyroid disorder than with PC (P < 0.001). The incidence of laterocervical lymph node pathology on diagnosis was significantly higher for DSV (P < 0.05). In 3.6 per cent of PC patients and 15.7 per cent of DSV patients, we observed recurrences in the regional lymph nodes (P < 0.001). We found 1.2 per cent distant metastases in PC patients and 7.2 per cent in DSV patients (P < 0.05). One PC patient (0.6%) and three DSV patients (3.6%) died of tumor-related causes (P < 0.05). Our study demonstrated that diffuse sclerosing carcinoma leads to a poorer prognosis to the extent that its classification as an autonomous clinical pathological entity is justified. In conclusion, we can state that DSV is a form of papillary thyroid tumor characterized by its higher aggressiveness, diffuse intrathyroid growth, and high incidence of lymph node and pulmonary metastasis. Ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biological aggressiveness, adequate postoperative treatment and close follow-up become essential.

The sentinel lymph node in papillary cancer of the thyroid including histological subtype.

BACKGROUND: The aim of this work was to reveal through sentinel node study the intraoperative presence of preoperatively undetected pathological lymph nodes. MATERIALS AND METHODS: At the Surgical Science Department of La Sapienza University of Rome The Authors studied from January 2003 to June 2004 18 patients with papillary carcinoma of the thyroid, who presented no clinical evidence of lymph node metastasis; they performed a total thyroidectomy in all cases, removing and histologically examining all lymph nodes of the upper anterior mediastinum. Where negative they were then subjected to immunohistochemical analysis with Pan Cytokeratin. RESULTS: The method was positive in 10 patients: 2 pure papillary carcinomas, 1 papillary carcinoma with poorly differentiated areas, 1 tall cell papillary carcinoma, 5 sclerosing carcinoma and 1 follicular variant papillary carcinoma; and negative in 8:5 pure papillary carcinomas, 2 sclerosing carcinoma and 1 case of follicular variant papillary carcinoma. Lymph node micrometastasis was found in 2 cases through study with Pan Cytokeratin on final histological examination. CONCLUSIONS: Analysis of the Authors' preliminary data shows that sentinel lymph node detection has 83.3% sensitivity and 100% specificity for Upper Anterior Mediastinum lymph nodes. The Authors can propose two main applications: select for dissection only patients with a positive sentinel node and reduce the number of cases to be subjected to postoperative treatment with iodine ablation, in patients with "low risk" thyroid tumours and negative sentinel nodes.

Comparison of extracellular matrix and apoptotic markers between benign lesions and carcinomas in human breast.

The expression of the extracellular matrix-related genes, such as fibronectin, laminin and tenascin C, and apoptosis-related genes, such as bax, bcl2 and survivin, was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and by immunohistochemistry in normal breast tissue and benign and malignant breast tumors and then correlated to several clinical parameters: estrogen and progesterone receptors, Ki67, ErbB2, tumor size, lymph node status and grading. Seventy-three breast tissue samples were examined. After RNA extraction, an RT-PCR was performed to detect fibronectin, laminin, tenascin C, bax, bcl2 and survivin gene expression. Thirty-two samples were evaluated also by immunohistochemistry at the protein level to detect fibronectin, laminin, tenascin C, bax and survivin. We found a significant correlation (P=0.025) between fibronectin gene expression and lymph node status, and a significant negative correlation (P=0.049) between laminin gene expression and Ki67. In addition, we found a statistically significant increase in survivin transcription in malign tumors compared to fibroadenomas (P=0.024). The negative correlation between laminin transcription and Ki67 could suggest that laminin impacts negatively on tumor proliferation, and the positive correlation between fibronectin and lymph node status may lead to consider fibronectin as predictive of long distance metastasis.

Epithelioid haemangioendothelioma of the parotid salivary gland: a case report.

Haemangioendothelioma is a vascular tumour characterised by the proliferation of endothelial cells with an epithelioid appearance. The behaviour of this neoplasm is intermediate between haemangioma and angiosarcoma. It may be localised in a wide range of sites, with a preference for soft and bone tissue. It is only rarely localised in the head and neck and even more rarely in the salivary glands. We describe a case of haemangioendothelioma in a 28-year-old man that originated in the retroneural region of the parotid gland, compressing the gland tissue and posteriorly infiltrating the muscular plane. A total parotidectomy surgical operation including the removal of lymph nodes in the region was performed followed by radiotherapy. An immunohistochemical investigation, carried out using the oxidase-antiperoxidase method, indicated that the neoplastic elements of the marker of the endothelial cells CD34 were positive for vimentine and for muscle-specific actin, showing a moderate proliferative action of the cellular elements with MIB-1 positivity estimated at around 6%. The peculiarity of the case we describe resides in the rarity of the haemangioendothelioma localisation in the parotid gland.

Prognostic importance of histologic vascular invasion in papillary thyroid carcinoma.

OBJECTIVE: To conduct a retrospective study of 39 patients with papillary carcinoma of the thyroid with histologic vascular invasion (VI+) and 361 patients without any sign of vascular invasion (VI-). SUMMARY BACKGROUND DATA: In the present study, we undertook a retrospective analysis of papillary carcinoma of the thyroid to assess whether histologically determined vascular invasion can be considered a predictive factor for prognosis. METHODS: By means of a retrospective study, we evaluated the department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1993 to December 1999. RESULTS: Group I consisted of papillary carcinoma without any sign of vascular invasion (VI-) comprising 361 patients. Group II consisted of papillary carcinoma with vascular invasion (VI+) comprising 39 patients. At the time of diagnosis, we observed no metastases in patients with VI-, whereas a pulmonary metastasis was observed in 1 patient with VI+ (P = 0.0023). In 3.6% patients with VI- and in 20.5% patients with VI+, we observed recurrences in the regional lymph nodes (P < 0.001); we observed 6 (1.66%) distant metastases in patients with VI- and in the 12.8% patients with VI+ (P < 0.001). Three patients with VI+ (7.7%) and 2 patients with VI- (0.6%) died of tumor-related causes; these figures were found to be statistically significant (P < 0.001). CONCLUSIONS: In papillary carcinoma, it should be noted that histologic vascular invasion may be considered as a sign of an increased tendency toward hematogenic invasion and consequent increase in the relative percentage of metastases; ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biologic aggressiveness, adequate postoperative treatment and close follow up become essential.

Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid.

Met protein, the high affinity receptor for hepatocyte growth factor (HGF), was highly expressed by the tumour cells of 64 well-differentiated papillary carcinomas of the thyroid. The p145 mature form and the p170 precursor form of the protein were both isolated from the tumours. Enhanced expression of Met protein was associated with a 9.5 +/- 5-fold increase in MET RNA transcript levels, suggesting increased transcription of the gene. In the same tumours, the levels of RNA transcripts for hypoxia inducible factor-1 (HIF-1), a potent stimulator of met gene transcription, were 4.5 +/- 3-fold higher than those present in the surrounding normal thyroid tissues. HIF-1 is generally induced by hypoxia. Histological features suggestive of a hypoxia were observed in 37 of 50 tumours and included coagulative necrosis, psammoma bodies, cystic changes, intratumoural haemorrhage, and hyalinization of the fibrous stroma. Immunostaining for Met protein was particularly intense in some cells located at the tumour periphery which were characterized by an invasive phenotype. Microdissection of tumour cell nests from the invading front revealed that the levels of RNA transcripts for MET/HIF were higher than in the centre of the tumour in four of nine cases. Taken together, the findings of this study suggest that HIF-1, perhaps driven by hypoxia, may be one of the factors leading to the increased transcription of met gene in papillary carcinoma and that this event is often more pronounced at the tumour periphery.