Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Age does not influence early and late tumor-related outcome for bronchogenic carcinoma

BACKGROUND: The influence of age on early and late outcome after surgical resection of bronchogenic carcinoma is unknown. In an attempt to clarify this issue, we reviewed the outcome of 212 consecutive patients with primary lung cancer who had surgical treatment for bronchogenic carcinoma. METHODS: Ninety-two patients were younger than 50 years (group 1), and 120 patients were older than 70 years of age (group 2). Squamous cell carcinoma and adenocarcinoma were the most common histologic types in both groups. According to the new international staging classification, a similar proportion of stage I, II, and III were observed in both groups. RESULTS: Only the rate of pneumonectomy was significantly higher in younger patients (41% versus 22%, p = 0.002). The overall operative mortality rate in group 1 was 2.2% and 2.6% after pneumonectomy. In group 2 the overall mortality rate was 2.5% and 3.8% after pneumonectomy. Advanced age did not affect operative mortality. The adjusted (tumor-related) survival rate at 5 years was 56% in group 1 and 53% in group 2 (p = 0.93). The adjusted survival rate for patients with stage I was 61% in group 1 and 65% in group 2 (p = 0.21), and for stage IIIa 39% in group 1 and 48% in group 2 (p = 0.43). The adjusted 5-year survival rate was 56% in group 1 and 59% in group 2 for squamous cell carcinoma (p = 0.53) and 49% in group 1 and 42% in group 2 for adenocarcinoma (p = 0.76). CONCLUSIONS: Perioperative risk and midterm survival were similar in younger and older patients after surgical resection of bronchogenic carcinoma. We believe that this result is because surgical candidates constitute already a highly selected group of patients. From these data it is not possible to conclude that biologic behavior of lung cancer is more aggressive in younger patients.     

Follow-up and management of patients exposed to a flawed automated endoscope washer-disinfector in a digestive diseases unit.

The possible transmission of pathogens to 236 persons exposed to an endoscope processed in a flawed automated endoscope washer-disinfector in a gastrointestinal endoscopy unit was investigated. During 6 months, 197 patients (83.5%) were followed up, and no cases of acute human immunodeficiency virus, hepatitis C virus, or hepatitis B virus infection were observed. This event created the conditions for improvements in safety procedures.     

Netrin-1 acts as a survival factor for aggressive neuroblastoma

Neuroblastoma (NB), the most frequent solid tumor of early childhood, is diagnosed as a disseminated disease in >60% of cases, and several lines of evidence support the resistance to apoptosis as a prerequisite for NB progression. We show that autocrine production of netrin-1, a multifunctional laminin-related molecule, conveys a selective advantage in tumor growth and dissemination in aggressive NB, as it blocks the proapoptotic activity of the UNC5H netrin-1 dependence receptors. We show that such netrin-1 up-regulation is a potential marker for poor prognosis in stage 4S and, more generally, in NB stage 4 diagnosed infants. Moreover, we propose that interference with the netrin-1 autocrine loop in malignant neuroblasts could represent an alternative therapeutic strategy, as disruption of this loop triggers in vitro NB cell death and inhibits NB metastasis in avian and mouse models.Dependence receptors now number more than a dozen, including deleted in colorectal cancer (DCC) (1), UNC5H (2), Patched (3), some integrins (4), neogenin (5), p75^NTR (6), RET (7), ALK (8), and TrkC (9). Although they have no structural homology (other than possibly in a domain referred to as the DART [dependence-associated receptor transmembrane] domain) (10), they all share the functional property of inducing cell death when disengaged from their trophic ligands, whereas the presence of their trophic ligands blocks this proapoptotic activity. Such receptors thus create cellular states of dependence on their respective ligands (11, 12).The prototype dependence receptors are the netrin-1 receptors. Netrin-1, a diffusible laminin-related protein, has been shown to play a major role in the control of neuronal navigation during the development of the nervous system by interacting with its main receptors, DCC (13, 14, 15) and UNC5H (16, 17). However, DCC and UNC5H (i.e., UNC5H1, UNC5H2, UNC5H3, and UNC5H4) have been shown to belong to the dependence receptor family (1, 2). This dependence effect upon netrin-1 has been suggested to act as a mechanism for eliminating tumor cells that would develop in settings of ligand unavailability (for reviews see references 18, 19). Along this line, disruption of the proapoptotic signaling of these netrin-1 receptors in the gastrointestinal tracts of mice, by netrin-1 overexpression or by inactivation of UNC5H3, is associated with intestinal tumor progression (20, 21).Thus, loss of the dependence receptors'' proapoptotic activity represents a selective advantage for tumor cells. In this respect, DCC was proposed in the early 1990s to function as a tumor suppressor gene, whose expression is lost in the vast majority of human cancers (22, 23). This hypothesis also fits with the observation that UNC5H genes are down-regulated in most colorectal tumors, hence suggesting that loss of UNC5H genes represents a selective advantage for tumor development (21, 24, 25). We have analyzed expression of netrin-1 and its receptors in neuroblastoma (NB), the most frequent extracranial solid tumor of early childhood. The aggressive and metastatic stage 4 NB displays three distinct clinical patterns at presentation and dissemination sites based on patients'' ages. Indeed, neonates and infants (<1 yr of age) with stage 4S and stage 4 without 4S features have an overall good prognosis, whereas stage 4 in children (>1 yr of age) shows a poor prognosis. We describe in this paper that, rather than the loss of netrin-1 receptor expression, a large fraction of aggressive NBs has evolved to select a gain of ligand expression that apparently represents a similar selective growth advantage. We therefore propose to use disruption of this selective advantage as an anticancer strategy in NB.     

Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.