Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

Abstract

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 (MeImAA). 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 sstr_1–5. 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.

Highlights of the biology of endocrine tumours of the gut and pancreas.

“…The positive assessment of endocrine differentiation of tumours requires the identification of general markers of neuroendocrine differentiation by immunohistochemistry (Bishop et al 1988). Widely used are cytosol markers such as neuron-specific enolase (NSE) (Bishop et al 1982) and protein gene product 9.5 (PGP 9.5) (Rode et al 1985), the membrane-bound neural cell adhesion molecules (NCAM) (Al-Khafaji et al 1998, Lantuejoul et al 1998, or granule markers such as chromogranin A and the ATP-dependent vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) (associated with large, dense-core vesicles) (Lloyd & Wilson 1983, Rindi et al 1986, Erickson et al 1996, Kolby et al 1998, Eissele et al 1999, Rindi et al 2000 and synaptophysin (associated with small synaptic-like vesicles) (Jahn et al 1985, Wiedenmann & Franke 1985, Buffa et al 1988. The identification of specific tumour cell types requires hormone immunohistochemistry, searching first for hormones expressed by the DES cells of the anatomical district where the tumour is found and then for 'ectopic' hormones according to specific hyperfunctional syndromes (e.g.…”

Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours

“…Very occasionally, (less than 1%), patients may complain of flushing and present with the 'atypical carcinoid syndrome' (7,8). Type 1 GCs occur more frequently in women in the fifth and seventh decades (9,10).…”

Histidine Decarboxylase Expression as a New Sensitive and Specific Marker for Small Cell Lung Carcinoma

“…Histamine plays a major role in allergy, inflammation, and cardiovascular hemodynamics (13)(14)(15), and histamine and other factors released from carcinoid tumor are related to the clinical condition known as carcinoid syndrome (16,17). Recent studies have also suggested a potential role of histamine in the proliferation of some types of human tumor cells via auto/paracrine activity (18 -20).…”