Hepatic small vessel neoplasm, a rare infiltrative vascular neoplasm of uncertain malignant potential

Abstract

Characteristic but rare vascular neoplasms in the adult liver composed of small vessels with an infiltrative border were collected from an international group of collaborators over a 5-year period (N=17). These tumors were termed hepatic small vessel neoplasm (HSVN), and the histologic differential diagnosis was angiosarcoma (AS). The average age of patients was 54years (range, 24-83years). HSVN was more common in men. The average size was 2.1cm (range, 0.2-5.5cm). Diagnosis was aided by immunohistochemical stains for vascular lineage (CD31, CD34, FLI-1), which were uniformly positive in HSVN. Immunohistochemical stains (p53, c-Myc, GLUT-1, and Ki-67) for possible malignant potential are suggestive of a benign/low-grade tumor. Capture-based next-generation sequencing (using an assay that targets the coding regions of more than 500 cancer genes) identified an activating hotspot GNAQ mutation in 2 of 3 (67%) tested samples, and one of these cases also had a hotspot mutation in PIK3CA. When compared with hepatic AS (n=10) and cavernous hemangioma (n=6), the Ki-67 proliferative index is the most helpful tool in excluding AS, which demonstrated a tumor cell proliferative index greater than 10% in all cases. Strong p53 and diffuse c-Myc staining was also significantly associated with AS but not with HSVN or cavernous hemangioma. There have been no cases with rupture/hemorrhage, disseminated intravascular coagulation, or Kasabach-Merritt syndrome. Thus far, there has been no metastasis or recurrence of HSVN, but complete resection and close clinical follow-up are recommended because the outcome remains unknown.

Keywords: Angiosarcoma; GNAQ; Hemangioma; Hepatic small vessel neoplasm; Liver.

Fig. 1

HSVN gross photograph (after fixation) demonstrates a mottled tan brown unencapsulated tumor with a poorly circumscribed border (image courtesy of Dr Gretta Jacobs, Cleveland, OH).

Fig. 2

HSVN, representative images. A, HSVN composed of thin-walled small vascular spaces with an indistinct border (H&E stain, original magnification ×20). B, HSVN demonstrating extensive infiltration into sinusoids and around steatotic parenchyma (H&E stain, ×100). C, HSVN, on biopsy, with parenchymal infiltration (H&E stain, ×200). D, HSVN composed of small vessels lined by flat to plump oval tumor cells with infiltration into sinusoidal space at edge of the tumor (H&E stain, ×400). E, HSVN with extramedullary hematopoiesis (H&E stain, ×400). F, Expanded hepatic plates adjacent to HSVN (reticulin stain, ×400).

Fig. 3

HSVN immunohistochemical staining with vascular markers. A, CD34 immunohistochemical stain demonstrates tumor infiltrating around portal tracts (×100). B, Fli-1 immunohistochemical stain highlights tumor infiltrating through fatty hepatic parenchyma (×100).

Fig. 4

HSVN with embolization material but no evidence of treatment effect (H&E stain, ×100).

Fig. 5

Immunohistochemical stains to distinguish HSVN from hepatic AS. A, HSVN with a low proliferative index (Ki-67 labels luminal extramedullary hematopoiesis) (Ki-67 immunohistochemical stain, ×400). B, Hepatic AS with a high proliferative index (Ki-67 immunohistochemical stain, ×400). C, HSVN with absent p53 staining (p53 immunohistochemical stain, ×200). D, Hepatic AS with strong nuclear p53 staining (p53 immunohistochemical stain, ×200).

Fig. 6

Cavernous hemangioma variants, 2 different cases (A and B) distinct from HSVN, with intermixed variably sized vessels and well-circumscribed borders (demonstrated in the lower right hand corner of [B]) (H&E stains, ×100).