Role of desmoplasia in recurrence of stage II colorectal cancer within five years after surgery and therapeutic implication.

BACKGROUND: Colorectal cancer (CRC) metastasis is enhanced in patients with venous embolization increasing the risk of recurrence and therefore mortality rate. Several evidences indicate that stage II patients have an abrupt recurrence within five years from surgery. This fact, led us to investigate the role played by different histological variables on CRC invasiveness. AIM: To demonstrate if quantitative and qualitative desmoplastic response and lymphocytic infiltration are prognostic factor involved in the recurrence of CRC within five years from surgery, considering possible clinical and therapeutical implications. METHODS: Thirty-four patients with CRC underwent colectomy and the UICC-TNM classification was applied for disease staging. Histological variables were semi-quantitatively evaluated. Qualitative evaluation of desmoplasia was obtained with the hematoxillin-eosin method. RESULTS: Survival rate arose 88% at stage II, at five years of follow-up, and the 12% not treated with adjuvant chemotherapy developed metastasis. Desmoplasia is strongly associated with venous neoplastic invasiveness (OR: 21.93; 95%CI: 1.012-475.26, p = 0.02), and therefore, with mortality rate (OR: 14.33; 95%CI: 0.67-304, p = 0.04). Moreover, mortality rate was significantly higher in patients with immature desmoplasia compare to mature stromal tissue (OR: 15.61, 95%CI: 0.69-343.38, p = 0.04). CONCLUSIONS: These observations should prompt a future evaluation of desmoplasia to extent more suitably the use of adjuvant chemotherapy in II stage patients. Further clinical trials are needed to determine if these findings will be able to reduce mortality rate, in stage II CRC patients.

Epithelial splenic cysts.

BACKGROUND: Epithelial splenic cysts (ESC) are uncommon lesions of the spleen. The etiopathogenesis of these cysts is controversial, even if Burrig's theory is the most accredited. The histological distinction between epidermoid and mesothelial cysts may be difficult, particularly for monostratified epithelium. PATIENTS AND METHODS: In the period between January 1986 and February 2004, 11 patients with ESC were studied. The history, physical findings, all relevant diagnostic studies and treatment were reviewed. All histological material was reviewed in detail with immunohistochemistry for CEA, CA 19-9, cytokeratin and calretinin. RESULTS: Epidermoid cysts were positive for CEA, CA 19-9, and cytokeratin, but negative for calretinin. Mesothelial cysts were positive for cytokeratin and calretinin, but negative for CEA and CA 19-9. CONCLUSION: Immunohistochemistry allows differential diagnosis between epidermoid and mesothelial cysts. With regard to etiopathogenesis, these data could mean that epidermoid and mesothelial cysts have distinct origins, though at variance with Burrig's theory. Although the ESC in this series were treated by open splenectomy, the recent approach by conservative and laparoscopic techniques offers great promise.

Evaluation of CD44 variant 6 expression and clinicopathological factors in pulmonary metastases from colon carcinoma.

Although relatively little is known about the molecular mechanisms underlying tumor progression, recently CD44 glycoproteins and the c-Met receptor tyrosine kinase have been identified as potentially important components of the metastatic cascade. CD44 is a family of transmembrane receptors generated from a single gene by alternative splicing and differential glycosylation. Important biological processes involving CD44 glycoproteins include cell adhesion, lymphocyte homing, hematopoiesis, tumor progression and metastasis. The precise mechanism via which CD44 promotes tumorigenesis have not yet been elucidated. We evaluated the expression of adhesion molecule CD44 variant 6 in pulmonary metastases from colorectal carcinomas and its correlation with clinicopathological parameters. Twenty patients were randomly selected from the patients who had undergone a resection of pulmonary metastasis from colorectal cancer. Formalin-fixed, paraffin-embedded archival specimens of tumor tissues and adjacent normal mucosa from these patients were the subjects of the present study. Immunoreactivity for CD44 was quantified. Specimens were considered positive if almost 25% of the neoplastic cells were stained. CD44 v6 expression was related to the interval between colon resection and metastases diagnosis, the number of pulmonary metastases, and the survival after lung resection. No statistical correlation was found between CD44 v6 positivity and disease-free interval after colon resection, number of metastases or 2-year survival after lung resection. Probably CD44 v6 is necessary and sufficient to confer metastatic potential to carcinoma cells increasing the migration capacity and participating in invasion via changes in adhesion to the extracellular ligands, but is not necessary to modify the clinical history of the metastases. Therefore the evaluation of CD44 v6 expression in lung metastases does not influence the therapeutic scheme.

Squamocellular carcinoma and chondrosarcoma: a true pulmonary carcinosarcoma. Report of a case.

BACKGROUND: Carcinosarcoma is one of the less common tumors of the lung and is composed of a mixture of malignant epithelial and mesenchymal elements of the type ordinarily seen in malignancies of adults. The carcinomatous component is mostly epidermoid and sometimes adenomatoid or undifferentiated. The mesenchymal part is mostly a spindle cell sarcoma and sometimes a polymorphocellular sarcoma. Differentiation as osteosarcoma and chondrosarcoma is rare. CASE REPORT: This report describes the case of a patient with carcinosarcoma of the lung composed of epidermoid carcinoma and chondrosarcoma. A left hilar mass was incidentally diagnosed. The patient was submitted to surgical exploration and a left lower lobectomy with dissection of local lymph nodes was performed. At microscopy the tumor was composed of both epithelial and stromal malignant component. The epithelial component consisted of poorly-differentiated squamous cell carcinoma and the stromal component consisted of chondrosarcoma. He remains well 30 months later. CONCLUSION: The prognosis of patients with carcinosarcoma is not always unfavourable. Potentially curative surgical resections should always be attempted. Pathologists should be aware of a wrong diagnosis of undifferentiated small cell lung carcinoma which eliminates the patient from surgery.

Chemotherapy-induced radiation recall myositis.

Myofasciitis syndrome encompasses a group of disorders characterized by chronic inflammation and/or fibrosis of the subcutaneous septa and muscular fascia. We report on a patient in whom myositis was diagnosed in the areas previously irradiated for papillary thyroid carcinoma and anal canal carcinoma respectively 21 and 3 years after radiotherapy. We are not able to explain why myopathy developed at the same time in two different sites at a different interval from the two radiotherapic schemes. We can suppose that the patient developed a subclinical regional myopathy after the first radiotherapic scheme. Radiation induced heritable mutations within surviving cells that were unable to tolerate the second damage by systemic chemotherapy. It is unclear how radiosensitization correlates with an ability to reactivate latent effects in normal tissue. Physicians using chemotherapic radiosensitizers should be aware of their potential to induce a delayed form of radiosensitization. We report this case to encourage physicians to be alert to the knowledge of the clinical, histologic and morphologic characteristics of radiation myositis in order to distinguish it from an infectious or immune fasciitis or myositis.

P53 as a marker of differentiation between hyperplastic and adenomatous parathyroids.

Primary hyperparathyroidism is the clinical result of parathyroid adenoma or hyperplasia, rarely of carcinoma. Clinical, serologic, and radiologic data are unable to discriminate a single parathyroid adenoma from an enlarged hyperplastic gland. Morphologic features also overlap in adenoma and small hyperplastic gland. Studying immunohistochemical expression of fatty acid synthase (FAS), p53, Ki67 and bcl-2, we found that among 21 adenomas 19 (90.5%) were positive for FAS, 12 (57.2%) for Ki67, 11 (52.4%) for p53, and 16 (76.2%) for bcl-2; among 12 hyperplasias, 12 (100%) were positive for FAS, 6 (50%) for KI67, 8 (66.7%) for p53, and 8 (66.7%) for bcl-2. Statistical analysis showed that FAS was associated with parathormone (PTH) (P =.001), Ki67 (P =.01), and p53 (P =.01). Moreover, FAS was associated with hyperplastic (P =.0001) and adenomatous glands (P =.0001). Ki67 was associated with both adenomatous (P =.02) and hyperplastic glands (P =.005). P53 protein were associated only with hyperplastic glands (P =.01). The different occurrence of p53 in parathyroids adenoma and hyperplasia may enable a different management and follow-up of the patients with primary hyperparathyroidism, stratifing them into two groups. The first, with a "false" adenoma having a high risk of relapse, may necessitate exams like serum calcium levels, PTH concentrations, urinary calcium levels for 24 hours, kidney functional tests, and radiology and ultrasound every 3 to 6 months, whereas the second with "true" adenoma, at low risk of relapse, may be checked less frequently with serum calcium levels and PTH concentrations.

Correlation between chromogranin-A expression and pathological variables in human colon carcinoma.

BACKGROUND: The possible association between neuroendocrine pattern and cancer prognosis could have substantial clinical implications, but the studies performed have generated conflicting results. As chromogranin-A (CGA) and dense-core granules are expressed concordantly, CGA expression may be used as a marker for cells expressing the complete neuroendocrine cell phenotype. MATERIALS AND METHODS: Fifty-six patients with primary colon carcinoma who underwent potentially curative surgery were analyzed. For immunohistochemical study a monoclonal antibody specific for human chromogranin A was used. The tumor was considered positive when the number of CGA cells was higher than 10% in the section. The relation between CGA-positivity and depth of parietal invasion, lymph-node status and differentiation grade was examined. RESULTS: We observed positive immunostaining in 22 cases out of 56 (39.3%). Significant association was found between CGA-positivity and lymph-node metastasis. CONCLUSION: CGA overexpression could reflect a more aggressive tumor. If our results are confirmed, we should consider the CGA + colon cancer patients at risk for lymph-node disease and therefore include them in a adjuvant chemotherapeutic protocol.