Diffuse Gastric Ganglioneuromatosis: Novel Presentation of PTEN Hamartoma Syndrome-Case Report and Review of Gastric Ganglioneuromatous Proliferations and a Novel PTEN Gene Mutation

Abstract

Gastrointestinal ganglioneuromatous proliferations are rare, most often found in the colon, and are three types: polypoid ganglioneuromas, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. We present a case of diffuse ganglioneuromatosis in the posterior gastric wall in a nine-year-old female. To our knowledge, this is the first reported case of diffuse ganglioneuromatosis located in the stomach. Only six cases of gastric ganglioneuromatous proliferations have previously been reported, two in English and none were diffuse ganglioneuromatosis. A diagnosis of diffuse ganglioneuromatosis is relevant for patient care because, unlike sporadic polypoid ganglioneuromas or ganglioneuromatous polyposis, most are syndromic. Diffuse ganglioneuromatosis is commonly associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2b, and Cowden Syndrome, one of the phenotypes of PTEN hamartoma tumor syndrome. The patient had the noted gastric diffuse ganglioneuromatosis, as well as other major and minor criteria for Cowden syndrome. Genetic testing revealed a novel frameshift mutation in the PTEN gene in the patient, her father, paternal aunt, and the aunt's son who is a paternal first cousin of the patient.

Figure 1

(a) Esophageal squamous mucosa with upper keratinocytes showing “cleared out” cytoplasms, characteristic for glycogenic acanthosis, and a rare eosinophil, consistent with minimal reflux (H&E 20x). (b) PAS without diastase digestion showing granular magenta positivity in keratinocytic cytoplasms of the upper half of the squamous mucosa, typical for glycogenic acanthosis (PAS 20X). (c) PAS with diastase digestion showing absence of the positive magenta granularity in the keratinocytic cytoplasms of the upper half of the squamous mucosa, confirming glycogenic acanthosis (PASD 20x).

Figure 2

Upper endoscopy: (a) normal distal esophagus; and (b–d) gastric mass with pedicle.

Figure 3

(a) Gastric biopsy showing spindled cells in fascicles with slightly atypical nuclei in the mucosal lamina propria (H&E 20X). (b) Gastric biopsy with spindle cells in the lamina propria showing strong S100 protein positivity (S100 protein 20x).

Figure 4

(a) Gastric biopsy with only ganglion cell amongst spindle cells, tip of black arrow (H&E 20X). (b) Neuron specific enolase (NSE) marking the single ganglion cell in gastric biopsy (NSE 40x).

Figure 5

Partial gastrectomy specimen with ganglioneuromatous proliferation extending from the submucosa into the lamina propria splaying oxyntic mucosal glands. A few of the ganglion cells are annotated with arrows (H&E 4x).

Figure 6

(a) Frozen section taken at time of partial gastrectomy showing muscularis propria with a myenteric ganglioneuromatous proliferation. Arrows mark some of the ganglion cells (H&E 4x). (b) Higher power image of the gastric resection at frozen section confirming a myenteric ganglioneuromatous proliferation. Ganglion cells marked with arrows (H&E 10x).

Figure 7

Minimally invasive follicular thyroid carcinoma showing invasion completely through the fibrous capsule, arrows, but not into the thyroid parenchyma (H&E 10X); lower right inset shows nuclear features of follicular carcinoma; absent are the nuclear pseudoinclusions and nuclear grooves expected in the follicular variant of papillary thyroid carcinoma (H&E 60x).