Mixed endocrine tumors

Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.     

Mixed haplotypes and autoimmunity

Why do (NZB × NZW)F₁ mice develop an autoimmune lupus-like syndrome? The second exons of the II genes of NZB and NZW are identical to their counterparts of H-2^d and H-2^u haplotypes. Several lines of evidence suggest that this allows the production of a mixed haplotype molecule, I-Eα^dEβ², and that this molecule plays a key role in the developmental of autoimmunity.     

Mixed crypt cell carcinoma

Summary The clinicopathological features of six appendix and five bowel tumours with features of the so-called goblet cell carcinoid are described. By light microscopy, these tumours were composed predominantly of mucous cells, together with variable proportions of endocrine and Paneth cells. Immunohistochemical and ultrastructural study confirmed this impression and no amphicrine cells were seen. The clinical course of all cases arising in the bowel, and three out of six appendix tumours was characterised by an aggressive behaviour with the development of widespread lymphatic and often intraperitoneal metastasis, but liver metastasis occurred in only one instance. We conclude, both from this study and from a review of the literature, that the mixed crypt cell carcinoma forms a distinct clinicopathological entity justifying separate classification from adenocarcinoma and carcinoid tumour.     

Mixed respiratory virus infections

Mixed respiratory viral infections are double negative common and evidence that they are associated with severe disease is supported by some groups. This controversial observation can be explained by the lack of sensitivity of the assessed methods used for viral identification and by the small number of patients included in the randomized cohorts studied. Most studies showed that respiratory syncytial virus (RSV) is identified in about 70% of hospitalized infants with bronchiolitis during seasonal winter epidemics, followed by human metapneumovirus (hMPV, about 3-19%) or rhinoviruses (about 20%). Other respiratory viruses have also been reported, indicating significant causes of bronchiolitis and hospitalization during seasonal epidemics. The presence of more than one pathogen, and moreover, the association of RSV with rhinoviruses and also RSV with hMPV, may influence the natural course of bronchiolitis. A better understanding of these various interactions would help future decision-making, such as the extent to which searches for co-pathogens should be conducted in severe bronchiolitis patients already infected by RSV.     

Mixed tumor of the mediastinum

A 36-year-old asymptomatic man was found to have a large middle mediastinal mass on a chest x-ray film. At surgery the tumor was located adjacent to the carina and beneath the aortic arch. It measured 7.0 X 5.0 X 4.0 cm and was well circumscribed and soft, with mucoid areas. The histologic features were those of a benign pleomorphic adenoma of salivary gland origin. This is, to our knowledge, the first reported case of primary pleomorphic adenoma of the mediastinum. We propose an origin from the ectopic salivary gland tissue. We also describe an additional patient in whom ectopic benign salivary gland tissue was found within mediastinal lymph nodes to support our hypothesis.     

Mixed tumour of the vagina

A 33-year-old Japanese woman presented with a polypoid 2.5 × 2.5 × 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal-type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal-type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial-myoepithelial combination in the glands as seen in so-called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha-smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.     

Mixed pulmonary blastoma and carcinosarcoma

Pulmonary blastemas and carcinosarcomas are uncommon tumours, accounting for less than 1% of all lung neoplasms. Three previously described mixed epithelial and mesenchymal tumours having both adult and embryonal elements were termed 'transitional'. We report a similar case and evaluate the application of the term 'transitional tumour'.     

Mixed hepatoblastoma in an adult

We report a case in an elderly adult of a highly malignant liver tumor with blastoid features that resembled hepatoblastoma. A liver tumor with a diameter of 23 cm was removed in a 78-year-old woman. The tumor showed highly differentiated epithelial hepatocellular and poorly differentiated epithelial and mesenchymal components. The blastoid nature and pluripotent differentiation potential were supported by immunohistologic analysis and suggest an origin of a poorly differentiated pluripotent hepatic cell with the potential to mature. We believe that this case of a mixed hepatoblastoma in an adult should be added to the growing number of presumed hepatic precursor cell neoplasms in adults.     

Mixed cryoglobulins and heterogeneity restriction

Cryoglobulins from 143 patients were analyzed using an immunoblot technique with a nitrocellulose membrane. Fifty-four p. cent of cases were classified as type III, with polyclonal IgG, IgA, and IgM being the most common components. Type II was found in 24% of cases, with a monoclonal IgM in most instances. Lastly, classification was impossible in 22% of cases, usually because of the presence of oligoclonal IgM bands. Use of this highly sensitive technique to analyse cryoglobulins raises the problem of identification of patterns that are difficult to include in types II and III.