Metastatic malignant melanoma of the gallbladder: a case report and review of the literature.

Both primary and metastatic melanoma of the gallbladder are rare. Involvement of the gallbladder occurs in about 15% of all gastrointestinal metastatic localizations in post-mortem case records. It is often difficult to differentiate primary from metastatic lesions on the basis of clinical, radiological and histopathological features. Melanoma involving the biliary tree seldom causes relevant symptoms during life, and this is why cases reported in the literature are few and those documented in living patients even fewer. We report a case of a young woman with a metastatic gallbladder melanoma who presented with a long and vague clinical history of symptoms that mimicked chronic cholecystitis with epigastric right hypochondrial pain without instrumental evidence of disease until the development of acute cholecystitis. We report this case to emphasize the need for awareness of the possibility of gallbladder involvement in the melanoma patient and to underline the necessity of meticulous investigation of unclear lesions of the gallbladder and biliary tree in patients with a past history of malignant melanoma. The clinical presentation, diagnosis, histopathology, prognosis and treatment of primary and metastatic melanoma of the gallbladder are also discussed and reviewed.

Changes in E-cadherin immunoreactivity in the adenoma-carcinoma sequence of the large bowel.

We have used an avidin-biotin immunoperoxidase technique to localise epithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, in 107 paraffin-embedded sections from 93 patients consisting of 24 with colorectal adenoma, 55 with rectal carcinoma and 14 with liver metastases. The corresponding primary colorectal tumours were also studied in these cases. E-cadherin was expressed by normal colorectal epithelial cells with typical membranous staining at the intercellular junctions. Loss of normal membranous E-cadherin expression and presence of cytoplasmic staining were found frequently in adenomas larger than 1 cm (P < 0.01), with high grade dysplasia and villous histology (P < 0.01). In primary rectal cancers, loss of membranous expression correlated with high tumour grade. No correlation was seen with Dukes and Jass stage, local extramural spread and 5-year recurrence rate. Complete loss of membranous E-cadherin immunoreactivity was seen in 7/14 (50%) liver metastases in which 6/7 (86%) showed intense membranous E-cadherin immunoreactivity in the corresponding primary tumour. Our data indicate that changes in E-cadherin immunoreactivity and cellular localisation correlate with size, severe dysplasia in adenomas and tumour grade in carcinomas. However, there seems to be no correlation between loss of membranous E-cadherin immunoreactivity and the invasive and metastatic potential of the carcinomas.

Unique genotypic features of infant acute lymphoblastic leukaemia at presentation and at relapse.

Acute lymphoblastic leukaemia (ALL) of infants aged less than 1 year represents a group of patients with peculiar biological features, poor response to therapy and unfavourable prognosis. In order better to characterize this type of leukaemia, we have investigated the immunoglobulin (Ig) and T-cell receptor (TCR) genes configuration of 21 infants with ALL, and compared the genotypic features with the phenotypic and karyotypic data, as well as with the clinical outcome. All cases had a pre-B phenotype; 12 (57%) of them were pre-pre-B ALL (CD10-, CD19+). Six of the 16 cases evaluated (38%) displayed chromosomal abnormalities; five had the typical translocation t(4;11)(q21;23). Eleven cases presented with a white blood cell count greater than 100 x 10(9)/l. The clinical course was unfavourable in 14 patients. The genotype of this group of ALL revealed several peculiarities. (1) Of the 21 cases, six (29%) displayed a multiple rearrangement pattern at the IgH locus. (2) In three cases (15%), the light chain genes were rearranged. (3) The TCR beta and gamma genes were rearranged in only one case (one case at the TCR beta and one at the TCR gamma locus). (4) The TCR delta chain was rearranged in eight cases (40%) and rarely deleted; the rearrangements observed were those most frequently observed in B cell-precursor ALL. Two cases were evaluated both at presentation and at relapse. While the immunophenotype had remained unmodified, comparison of Ig heavy chain gene rearrangements revealed clonal variations in both cases. Taken together, these findings further underline the biological peculiarities of infant ALL compared to ALL which occurs in older children and in adults, and stress the need of differentiated and aggressive therapeutic approach for these patients.

Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of molecular lineage commitment and association with poor prognostic features.

The authors studied six adult patients with acute leukemia with these unusual characteristics: unclassifiable morphology and undifferentiated cytochemistry by French-American-British (FAB) criteria; concurrent expression of CD13 (and CD33) myeloid and early T-cell CD7 immune markers; no evidence of T-cell lineage commitment as determined by T-cell receptor beta (beta), gamma (gamma), and delta (delta) chain gene rearrangement study and cytoplasmic CD3 epsilon expression; and no evidence of myeloid cell lineage commitment, as shown by absent myeloid-specific c-fms proto-oncogene expression and negative myeloperoxidase ultrastructural staining (one case). Clinically, these diagnostic features matched with a poor prognosis, being associated with refractoriness to treatment, relapse and progression of disease, antecedent hematologic abnormality, and other malignancy. These cases may represent a distinct stem cell leukemia syndrome deserving immediate recognition and a nonconventional chemotherapeutic approach.

Effects of cefodizime on non-specific immune functions in patients with multiple myeloma.

The effects of cefodizime (CDZ) on non-specific immunity in patients with multiple myeloma were studied in a randomized, placebo-controlled trial. A total of 51 patients with newly diagnosed multiple myeloma were admitted to the study, 27 of whom received CDZ 2 gi.v. once daily for seven days and 24 ascorbic acid 1 g daily i.v. for one week. Granulocyte chemotaxis, neutrophil biochemiluminescence and phagocytosis were determined at baseline, and at 48 h after the last dose. At baseline, chemiluminescence, phagocytosis and, to a lesser extent, granulocyte chemotaxis were diminished in both patient groups compared to healthy volunteers. After treatment, a significant increase in chemiluminescence and phagocytosis was observed in the CDZ group, while a slight increase in granulocyte chemotaxis did not reach statistical significance. No changes were observed in the control group. It is concluded that CDZ enhanced non-specific immune mechanisms in patients with multiple myeloma.

Expression of lineage-restricted protein tyrosine kinase genes in human natural killer cells.

The hematopoietic lineage derivation, recognition structures and associated signal transduction pathways of CD3- natural killer (NK) cells have not been identified. Protein tyrosine kinases (PTK) structurally related to the product of the c-src protooncogene are differentially expressed in distinct hematopoietic differentiation lineages and may participate in specific signal transduction pathways. The present study was aimed at characterizing the expression of src-related PTK genes in normal human NK cells and in cells from patients with CD3- granular lymphocyte proliferative disease. CD3- normal NK cells had high levels of transcripts of the lck gene, which is highly expressed in T cells. CD8+ and CD8- NK cells expressed similarly high levels of lck mRNA. In contrast, NK cells expressed very low levels (25-80 times less than monocytes) of mRNA encoding the myelomonocytic PTK hck. NK cells also expressed fyn transcripts (p59fyn reportedly associates with the T cell receptor in T cells) and fgr transcripts, the latter observation confirming a previous report. The pattern of expression of the lineage-restricted PTKs lck and hck in NK cells is consistent with the hypothesis of an ontogenic relationship of this population with the lymphocytic rather than myelocytic differentiation pathway. PTK expressed in NK cells may participate in signal transduction pathways in this cell population.