A large malignant insulinoma: case report with endosonographic, immunohistochemical and ultrastructural features

Abstract

Malignant insulinoma in the beta cells of the pancreatic islet is rare and usually presented as hypoglycemia. We report a case of large malignant insulinoma in a 53-year-old Korean woman. A presumptive clinical diagnosis was made before surgery, based on the high plasma insulin-to-glucose ratio and a large solitary heterogeneous pancreatic mass by abdominal computed tomography and endosonography. The tumor measured 5.8 x 4.7 x 4.5 cm in dimension and showed capsular invasions and metastases in two of four peripancreatic lymph nodes. The tumor cells were strongly immunoreactive to insulin and had a high Ki-67 labeling index (13%) and atypical membranous electron-dense granules, ranging from 120 to 400 nm in diameter, in the cytoplasm on electron microscopy. The patient was treated by distal pancreatectomy with splenectomy and rapidly recovered without neurohypoglycemic symptoms. This case showed not only lymph node metastases, the most reliable parameter for malignancy in pancreatic endocrine tumors, but also other valid diagnostic clues, such as high Ki-67 labeling index, heterogeneous enodosonographic findings, capsular invasions with large tumor and pure atypical secretory granules.

Figure 1.

Measurement of serum glucose on 72-hour fasting test. The arrow indicates the time-point of glucose administration

Figure 2.

Abdominal CT showed a single, round, well-enhanced mass in the tail of the pancreas, measuring 6 cm in diameter. Neither lymph node enlargement nor metastatic lesion was visible.

Figure 3.

Hypoechoic, heterogeneous with multiple anechoic spots and a smooth delineation without other intra-pancreatic occult mass were detected by EUS at a frequency of 7.5 MHz (G: stomach, M: mass, P: pancreas, S: superior mesenteric artery, V: splenic vein).

Figure 4.

The tumor mass was oval, well-demarcated solid, measuring 5.8×4.7×4.5 cm in dimension. Two foci of capsular invasion (arrowheads) were observed in the cut surface.

Figure 5.

The tumor demonstrated small nests of uniform bland cells septated by thin fibrovascular stroma (A). A peripancreatic lymph node was metastasized by tumor cells (asterisk) (B), (H&E. ×100).

Figure 6.

The cytoplasm of the tumor cells was strongly immunoreactive (dark-brown) for the insulin (A). A few tumor nuclei showed immunoreactive (dark-brown) for Ki-67 (B), (×200).

Figure 7.

EM demonstrated well-developed, membranous, electron-dense atypical secretory granules (SG) in the cytoplasm measuring 120 to 400 nm (A). There were wisps of non-branching intermediate amyloid filaments (asterisk) in the extracellular spaces (B). (M: mitochondria. Scale bar: 0.5 μm).

Figure 8.

Amyloid deposits near the vessels were exhibited yellow-green birefringence under polarizing microscopy (Congo red stain, ×200).