Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.
A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
Kölby
L
L
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Wängberg
B
B
Ahlman
H
H
Jansson
S
S
Forssell-Aronsson
E
E
Erickson
J D
JD
Nilsson
O
O
D000368:Aged; D001692:Biological Transport / Q000235:genetics; D015152:Blotting, Northern; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006632:Histamine / Q000032:analysis* / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011968:Receptors, Histamine / Q000032:analysis / Q000096:biosynthesis; D017481:Receptors, Somatostatin / Q000235:genetics*; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011968:Receptors, Histamine; D017481:Receptors, Somatostatin; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D006632:Histamine