August 2021 – Gastroenterology Pathology

The correct answer is: Peutz Jeghers Polyp.

The correct answer is Peutz Jeghers (PJ) polyp, which is a type of hamartomatous polyp associated with Peutz Jeghers syndrome (PJS). PJS is an autosomal dominant cancer syndrome, with a prevalence of 1 in 200,000 individuals. The underlying genetic abnormality is an inherited germline mutation in the STK11 tumor suppressor gene encoding a serine/threonine kinase. Individuals with PJS present with mucocutaneous melanin pigmentation, gastrointestinal polyps, and increased risk of cancer of the following sites (listed in decreasing order of cancer risk): breast, colorectal, pancreas, stomach, ovary, lung, small intestine, uterus, testis, and cervix. It is important to note that PJ polyps are typically not precancerous.^1,2  

Clinical diagnosis of PJS can be made, according to the WHO criteria, when a patient presents with three or more PJ polyps; one or more PJ polyps and a family history of PJS; mucocutaneous pigmentation and a family history of PJS; or one or more PJ polyps and mucocutaneous pigmentation.¹ It is important to note that PJ polyps can occur as a solitary polyp in individuals without a family history of PJS or mucocutaneous pigmentation. In this circumstance, the significance is uncertain; however, one study examined 51 patients with a solitary PJ polyp and found that 35% of the patients were diagnosed with cancer (gastrointestinal, breast, lung, thyroid, prostate, hypopharyngeal, and liver) prior to the identification of the PJ polyp. The study suggests that if a patient with a solitary PJ polyp undergoes complete evaluation of the gastrointestinal tract and no other polyps are found, then the patient may not require additional surveillance.³ Most likely the patient presented in the above vignette had a solitary PJ polyp. She was referred to department of genetics to determine the next course of action.

PJ polyps are predominately found in the small intestine, but occasionally can be identified in the colorectum and stomach. Histologically, small intestinal and colorectal PJ polyps exhibit a very characteristic villous architecture with smooth muscle cores arborizing throughout the polyp. Lobular crypt organization is also a helpful feature to diagnose PJ polyps, but is more frequently identified in colorectal PJ polyps.⁴ Cystically dilated glands with mucin and misplacement of epithelium due to prolapse can also be seen. The epithelium lining the polyp is small intestinal type or colonic epithelium, depending on the polyp’s site of origin. Dysplastic change within the epithelium is very rare. ¹

The histology seen in gastric PJ polyps is not as characteristic as seen in small intestinal or colorectal PJ polyps. The gastric PJ polyps frequently appear as juvenile polyps or sporadic hyperplastic polyps of the stomach.¹

Cowden syndrome (CS) is an autosomal dominant cancer disorder caused by a germline PTEN mutation. CS polyps are morphologically diverse and include the following: hyperplastic polyps, hamartomatous/juvenile polyps, adenomas, and ganglioneuromas.^1,5 Overall, hamartomatous CS polyps are more commonly found in the colon, are sessile, have a fibrotic lamina propria, and do not demonstrate surface erosion or cystically dilated glands. Specific features, if identified, that can help diagnose a CS hamartomatous polyp is the presence of ganglion cells and/or a nerve fiber proliferation in the lamina propria.^5,6

Juvenile polyposis syndrome (JPS) is another autosomal dominant cancer syndrome marked by a germline mutation in SMAD4 or BMPR1A.¹ JPS polyps are usually colorectal but can also occur in the stomach or small intestine. Colorectal JPS polyps are typically exophytic with smooth contours and cystically dilated glands filled with mucin. Surface erosion with edematous and inflamed lamina propria is frequently seen.^1,6,7 Gastric JPS polyps are difficult to differentiate from gastric hyperplastic polyps and gastric PJ polyps solely based on histology. Of note, SMAD4 immunohistochemical stain may be of benefit, as approximately 50% of JPS polyps will show loss of staining.¹

Intestinal-type adenoma with low-grade dysplasia is either a pedunculated or sessile polyp in the small intestine. Histologically, this polyp exhibits a tubular or tubulovillous growth pattern lined by intestinal-type epithelium, sometimes with a mixture of goblet cells, Paneth cells, or endocrine cells. Cytologically, the low-grade dysplastic epithelial cells, which is rare to see in PJ polyps, demonstrate polarized, enlarged, and elongated nuclei.¹ Importantly, the characteristic arborizing smooth muscle and lobulated crypt architecture of PJ polyps are absent.⁴

References

1. WHO Classification of Tumors Editorial Board. Digestive system tumors. Lyon (France): International Agency for Research on Cancer; 2019.
2. Beggs AD, Latchford AR, Vasen HF, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59(7):975-986.
3. Iwamuro M, Aoyama Y, Suzuki S, et al. Long-Term Outcome in Patients with a Solitary Peutz-Jeghers Polyp. Gastroenterology research and practice. 2019;2019:8159072.
4. Tse JY, Wu S, Shinagare SA, et al. Peutz-Jeghers syndrome: a critical look at colonic Peutz-Jeghers polyps. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2013;26(9):1235-1240.
5. Borowsky J, Setia N, Rosty C, et al. Spectrum of gastrointestinal tract pathology in a multicenter cohort of 43 Cowden syndrome patients. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2019;32(12):1814-1822.
6. Shaco-Levy R, Jasperson KW, Martin K, et al. Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Human pathology. 2016;49:39-48.
7. van Hattem WA, Langeveld D, de Leng WW, et al. Histologic variations in juvenile polyp phenotype correlate with genetic defect underlying juvenile polyposis. The American journal of surgical pathology. 2011;35(4):530-536.