The hypoxia-regulated transcription factor DEC1 (Stra13, SHARP-2) and its expression in human tissues and tumours

DEC1, also known as SHARP-2 or Stra13, is an important molecule in embryonic differentiation and has recently been identified to be strongly inducible by hypoxia. Its distribution in normal human tissues and most tumour types is unknown. In the present study, a polyclonal antiserum to a 10-amino acid peptide from DEC1 has been raised. Using this antiserum, DEC1 was shown to be widely expressed in most normal human tissues, but usually only in a proportion of cells and typically with a nuclear localization. In tumours, expression was either augmented (the commonest pattern) or occasionally decreased. Similarly, in most normal tissues, low or absent expression was observed in endothelial cells, whereas in many tumour samples endothelium was usually strongly positive. In tumours, there was a striking pattern of staining seen in connection with areas of necrosis, with absence of DEC1 expression within a zone of morphologically viable cells immediately adjacent to the necrotic zone. This suggests that while DEC1 may be up-regulated by hypoxia in cancer, in more extreme hypoxia it may have a role in cell death. Its interrelationship with other hypoxically regulated molecules, such as the hypoxia-inducible factors or carbonic anhydrase IX, and differentiation of tumours now requires further investigation.     

Neurogenic polyps

A neoplastic proliferation of peripheral nerve sheath cells (Schwann cells, fibroblasts and perineurial cells) and ganglion cells in the colorectum may give rise to the mucosal or submucosal polyps. Depending upon the predominant cell types, these neurogenic polyps can be classified as schwannomas, granular cell tumours, neurofibromas, perineuriomas, mixed nerve sheath tumours, ganglioneuromas or paragangliomas. Morphologically, the neoplastic cells repeat or mimic the corresponding nerve sheath cells or neurons in terms of growth pattern, histology and immunoreactivity. They are uncommon, but the polyps can occur in any age group, although the vast majority of patients are adults. The polyps can be either solitary (most peripheral nerve sheath tumours) or multiple, especially if associated with systemic diseases (i.e. syndromes involving the peripheral nerve tissue). They are usually incidental findings or may be accompanied by gastrointestinal symptoms. Almost all colorectal neurogenic polyps are benign, and they rarely undergo malignant transformation unless they are part of a syndromatic manifestation. However, these polyps may cause a diagnostic problem during screening for colorectal cancer. An accurate diagnosis of these entities will help clinicians to make appropriate management decisions.     

The pregnancy-associated α2-glycoprotein (α2-PAG) A tumour marker?

Summary Long-term studies of 2-PAG in sera of patients with breast cancer, bronchial carcinoma, gynaecological carcinoma, melanoma and laryngeal carcinoma have proved that 2-PAG is a possible laboratory parameter for the assessment of recurrence of tumour and metastasis. The results published for trophoblastic tumour and gastrointestinal carcinoma are still divergent. Because of the large individual range of 2-PAG concentrations and the widely differing 2-PAG levels in men and women single determinations of this protein are without value. A detailed classification of the pathological mechanisms to which these proteins are submitted is still missing and consequently we have no fundamental knowledge of diseases that apart from pregnancy and neoplasia lead to changes in the physiological 2-PAG serum concentration.Dedicated to Prof. Dr. E. Schmiedt to his 60th birthday (20th of November 1980)     

DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: Probably A different origin for infantile and adolescent germ cell tumours

The origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non-seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells. The presence of carcinoma in situ cells strongly suggested that the adolescent tumours arose from carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.     

Isolated diffuse hemangiomatosis of the spleen with Kasabach-Merritt-like syndrome

AIMS: Diffuse haemangiomatosis of the spleen is a rare benign vascular condition occurring as a manifestation of systemic angiomatosis or, less commonly, confined to the spleen. It is sometimes accompanied by severe disturbance of blood coagulation. The goal of this study was to characterize an additional case of isolated diffuse haemangiomatosis of the spleen and to determine the histogenesis of this lesion which remains obscure. METHODS AND RESULTS: We describe a case of isolated diffuse haemangiomatosis of the spleen in which histological and immunohistological findings suggested the possibility of a malformative tumour-like lesion. The pathological cavernous vessels were distributed randomly through the red pulp, without continuity with sinuses. The endothelial cells expressed vimentin, factor VIII related antigen and CD34, but not CD8. Some cells lining the sinus lumen expressed CD68, lysozyme and myeloperoxidase. In addition, trabecular veins presented with intimal thickening. These results allow making a diagnosis between diffuse haemangiomatosis and other tumours/tumour-like lesions of the spleen, especially littoral cell angioma, splenoma and peliosis. CONCLUSION: If diffuse haemangiomatosis is usually classified as a benign proliferation of endothelial cells, we suggest that diffuse haemangiomatosis, when confined to the spleen, could be a tumour-like vascular lesion. In this hypothesis, the aetiology may be hamartomatous or malformative as is suspected in arterio-venous haemangioma of the lower extremities. The histogenesis is still questionable and no definitive proof in favour of one or the other hypothesis has been reported.     

Precursor lesions of ovarian epithelial malignancy

Most ovarian carcinomas arise from the mesothelial surface lining of the ovaries, or from invaginations of this lining into the superficial ovarian cortex to form cortical inclusion cysts. The native ovarian surface mesothelium is of an 'uncommitted' phenotype, and has potential to modulate to epithelial or mesenchymal phenotypes in response to signals such as those associated with ovulation. The exposure of the mesothelial lining of an inclusion cyst to the ovarian stromal microenvironment may be responsible for the phenotypic change to Müllerian epithelium so commonly seen in these cysts. Müllerian metaplasia is usually to a serous phenotype, and it is possible that undefined molecular events occurring in an inclusion cyst that has undergone Müllerian metaplasia may initiate neoplastic change in these cysts. This may be the developmental pathway of most invasive serous carcinomas. Occasional rare cases of ovarian intraepithelial neoplasia, manifested by epithelial atypia in an inclusion cyst or on the surface epithelium without invasive carcinoma, are identified histologically. Serous borderline tumours represent a separate category and in most cases probably do not progress to frank carcinoma. Mucinous carcinomas may in some cases have arisen from pre-existing benign and borderline mucinous tumours. Endometriosis of the ovary is associated with genetic abnormalities and is frequently found in association with clear cell and endometrioid carcinomas, suggesting that in many cases these latter two types of carcinoma may have arisen directly from endometriotic deposits. Ovaries removed prophylactically from women with a family history of ovarian carcinoma or with a mutation in one of the genes predisposing to ovarian carcinoma should be processed in their entirety, and examined closely not just for obviously neoplastic lesions, but also for more subtle morphological abnormalities of the surface epithelium or the epithelium lining cortical inclusion cysts.     

Thymic neuroendocrine tumours

Thymic epithelial tumours include the subcategory of thymic neuroendocrine neoplasms, which comprise a spectrum of entities that mirrors their counterparts in the lung, i.e. typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma. These tumours are classified according to the current WHO classification for lung tumours, and their relevant histomorphological and immunohistochemical criteria will be discussed in this brief review. Thymic neuroendocrine neoplasms do, however, also have clinical and molecular characteristics which set them apart from their pulmonary relatives, and recent research has provided valuable insights into possible molecularly-informed classification systems, which broadly align with classical categories, but also show some discrepancies. The most salient recent studies in that respect will also be discussed, as will the avenues for locally ablative therapy and possibilities for systemic treatment.     

Synchronous primary mediastinal seminoma in a patient with colorectal adenocarcinoma

Primary mediastinal germ cell tumours are a rare primary tumour of the mediastinum. They share the same immunomorphological features to their gonadal counterparts but carry a worse prognosis. Primary mediastinal seminomas are exclusively found in male patients. Their diagnosis requires exclusion of primary gonadal germ cell tumours.