Mixed papillary transitional cell carcinoma and adenocarcinoma of the uterine cervix: a clinicopathologic study of three cases.

Although tumors consisting of a combination of transitional cell carcinoma (TCC) and adenocarcinoma have been described in the endometrium, they have not been documented in the uterine cervix to our knowledge. Three such cervical cases are reported in this article. Three patients, whose ages ranged from 40 to 61 years, presented with vaginal bleeding and malignant cells on routine Papanicolaou smears. The initial diagnoses based on a biopsy specimen were poorly differentiated squamous cell carcinoma in two patients and adenocarcinoma with a solid component in the third patient. All patients underwent radical hysterectomy. The hysterectomy specimens each contained a polypoid endocervical mass with minimal invasion of the cervical stroma. On microscopic examination, each tumor consisted of a component of papillary TCC admixed with an adenocarcinoma of endometrioid type. Both carcinomatous components were immunoreactive for cytokeratin (CK) 7 but not CK20. The three patients were alive and disease-free from 10 months to 4 years postoperatively. Recognition of this unusual variant of cervical carcinoma is important to delineate its clinical and pathologic features and establish prognostic differences, if any, from other histologic subtypes of cervical carcinoma. Papillary TCC mixed with adenocarcinoma broadens the morphologic spectrum of transitional cell neoplasms of the uterine cervix.     

Haematopoietic and immune defects associated with GATA2 mutation

Heterozygous familial or sporadic GATA2 mutations cause a multifaceted disorder, encompassing susceptibility to infection, pulmonary dysfunction, autoimmunity, lymphoedema and malignancy. Although often healthy in childhood, carriers of defective GATA2 alleles develop progressive loss of mononuclear cells (dendritic cells, monocytes, B and Natural Killer lymphocytes), elevated FLT3 ligand, and a 90% risk of clinical complications, including progression to myelodysplastic syndrome (MDS) by 60 years of age. Premature death may occur from childhood due to infection, pulmonary dysfunction, solid malignancy and MDS/acute myeloid leukaemia. GATA2 mutations include frameshifts, amino acid substitutions, insertions and deletions scattered throughout the gene but concentrated in the region encoding the two zinc finger domains. Mutations appear to cause haplo‐insufficiency, which is known to impair haematopoietic stem cell survival in animal models. Management includes genetic counselling, prevention of infection, cancer surveillance, haematopoietic monitoring and, ultimately, stem cell transplantation upon the development of MDS or another life‐threatening complication.     

Interdigitating dendritic cell sarcoma of the parotid gland: case report and literature review

Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from the antigen-presenting cells of the immune system. We report a case of IDCS occurring in a 69-year-old man who presented to an outside institution with a painless mass in his right parotid gland for several months. He presented to our institution after undergoing a superficial parotidectomy. A diagnosis of undifferentiated neoplasm, favoring poorly differentiated carcinoma, was made at that time. He underwent a total parotidectomy and neck dissection at our institution. Microscopically, the tumor was composed of atypical spindle cells involving the parotid gland and an ipsilateral level III lymph node. Immunophenotypic analysis demonstrated positive staining for S100, fascin, vimentin, and HLA-II. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Taken together, the above features were consistent with IDCS. An IDCS of the parotid gland is extremely rare, with only 2 cases reported in the literature. The unusual location and morphological similarity to follicular dendritic sarcoma and other types of soft tissue sarcomas can be a diagnostic challenge. Awareness of this tumor and the use of appropriate markers are crucial in making the diagnosis. The patient did well postoperatively, and he underwent a complete course of postoperative irradiation to the right parotid and neck.     

The allylic 7-ketone at the steroidal skeleton is crucial for the antileukemic potency of chlorambucil's active metabolite steroidal esters

We have investigated the role of the allylic 7-ketone in oxidized Delta5-steroids on antileukemic activity. We synthesized and studied a series of oxidized and non-oxidized steroidal esters of p-N,N-bis(2-chloroethyl)aminophenylacetic acid (PHE), chlorambucil's active metabolite. In a comparative study of these 7-keto derivatives, on a molecular basis, regarding their ability to induce sister chromatid exchanges (SCEs) and to inhibit cell proliferation in normal human lymphocytes in vitro, the results with these 7-keto derivatives, on a molecular basis, correlated well with their antileukemic potency against leukemia P388- and L1210-bearing mice, which proved to be significantly increased compared to that of the non-oxidized derivatives. Our results indicate that the role of the steroidal skeleton it is not only for the transportation of the alkylating agent into the cell, but also contributes directly to the mechanism of antileukemic action, by an as-yet unknown way. The main conclusion from this study is that the existence of the allylic 7-keto group in the skeleton of the Delta5-steroidal esters impressively enhances their antileukemic activity, while the toxicity remains at clinically acceptable levels, suggesting that this structural modification should be further investigated.     

Hepatic arterial resistive indices: Correlation with the severity of cirrhosis

Forty-three patients who were scheduled to undergo a percutaneous liver biopsy were evaluated with Doppler sonography to determine the hepatic arterial resistive index (RI). The histologic specimens were graded by a pathologist regarding cirrhosis and inflammation. The specimens demonstrated no cirrhosis in 12 of 43 (28%) patients, early cirrhosis in 10 of 43 (23%), and established cirrhosis in 21 of 43 (49%). Analysis also revealed that inflammation was absent in three of 43 (7%) patients, minimal in seven of 43 (16%), mild in 17 of 43 (40%), moderate in 13 of 43 (30%), and severe in three of 43 (7%). Hepatic artery RIs (without correction for heart rate) ranged from 0.64+0.06 in patients with early cirrhosis to 0.68 ±0.09 in patients with severe inflammation. There was no significant correlation between the degree of cirrhosis and/or inflammation and hepatic artery RI (with or without correction for heart rate). We conclude that Doppler determination of hepatic artery RIs is not a reliable method of predicting the severity of hepatic cirrhosis and/or inflammation.     

Hormone receptor status rather than HER2 status is significantly associated with increased Ki-67 and p53 expression in triple-negative breast carcinomas, and high expression of Ki-67 but not p53 is significantly associated with axillary nodal metastasis in triple-negative and high-grade non-triple-negative breast carcinomas

Triple-negative (TN) breast carcinoma is associated with a higher recurrence rate and shorter survival and lacks the benefit of specific therapy. TN tumors usually express high levels of Ki-67 and p53 that are considered prognostic markers for breast cancer. We compared Ki-67 and p53 expression between TN and high-grade non-TN invasive carcinomas in a total of 214 cases and investigated an association between their expression and axillary nodal metastasis in these tumors. Our findings demonstrate that TN tumors are associated with significantly higher expression of Ki-67 and p53 compared with non-TN tumors, which may contribute to the poorer prognosis in TN tumors. Hormone receptor negativity rather than HER2 negativity is associated with the significantly increased Ki-67 and p53 expression in TN tumors. Furthermore, a high expression level of Ki-67 but not p53 is more likely to be associated with axillary nodal metastasis in these cases.