Category Archives: Etiology of Cancer

Images of Peutz-Jeghers Syndrome

Below are images I had taken of a young woman (about 25yrs old). I do not remember what she was admitted for, but if I am not mistaken it was an illness unrelated to Peutz-Jeghers Syndrome (PJD), probably a febrile illness. A colleague of mine asked me if I had seen the circumoral pigmentations of PJD. Fortunately, I had been carrying my Nikon Coolpix 4500 on that day.

Circumoral Pigmentation

Mucosal Pigmentation

Jejunal Polyp

PJD is an autosomal dominant disease caused by germline mutations of the gene STK11 (also known as LKB1) located on the short arm of chromosome 19 (19p). It is characterized by mucocutaneous pigmentation, hamartomas of the gastrointestinal tract and a very risk of malignancy. STK11 mutations are not identifiable in about 25% of the patients. These patients are believed to have inactivation of the gene by other mechanisms. About ½ to 1/3rd of the patients have new mutations. The incidence of PJS ranges from 1 in 30,000 to 1:200,000 births

Pigmentation classically involves the lips and buccal mucosa but other areas including hands and feet but may be seen around the nose, orbits anus and genitals. It is caused by melanin. Spots present at birth but may fade with age and adults may not have the spots. About 5% patients do not have pigmentation.

PJS is associated with hamartomatous polyps. Hamartomatous polyps are polyps composed of the normal layers of the intestine but with a markedly distorted architecture. It results from an overgrowth and is not, at least initially, to have a malignant potential. The polyps may be pedunculated or sessile and vary in size from few mm to 3-4 cm. Eighty percent of the patients have jejunal polyps, 40% in the stomach and 40% in the colon. The PJD polyps have no distinctive endoscopic features but can be differentiated from other syndromes by distinctive histopathologic features of arborizing pattern of smooth muscle throughout the polyp. Patients usually present in the second decade of life with abdominal pain, rectal bleeding, anaemia, small intestinal intussusception, bowel obstruction, and rectal prolapse of polyps. Forty to fifty percent of patients need a surgery for polyp related bowel obstruction

From Peutz-Jeghers Syndrome in Familial Cancer Syndromes Editor Douglas L Riegert-Johnson. NCBI 2009

Patients of PJS are at a very high risk of malignancy and the risk is not confined only to the gastrointestinal tract. Almost all patients with PJS will develop a malignancy. PJS increases the risk of small intestinal carcinoma by more than 500 times. The risk of other gastrointestinal cancers, breast cancer, cancer of the uterus and ovary are also increased.

Cancer Cumulative Risk* Relative Risk#
All 93% 15.2
Oesophagus 0.5% 57
Stomach 29% 96
Small Intestine 13% 520
Colon 39% 84
Pancreas 36% 132
Lung 15% 17
Testis 9% NS
Breast 54% 15.2
Uterus 9% 16
Ovary 21% 27
Cervix 10% NS

Data sourced from * Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408-415.
# Giardiello FM, et al Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000 Dec;119(6):1447-53

PJD is treated by polypectomy that may be performed by intraoperative endoscopy or double balloon endoscopy. There are no recommendations for screening patients. The disease is rare and evolving formal recommendations will be difficult. Given below is a graphic compilation of screening recommendations from sources listed by Giardiello and Trimbat (see table above).

Internet resources for PJS include

  1. Peutz-Jeghers Syndrome in Familial Cancer Syndromes
    Editor Douglas L Riegert-Johnson. NCBI 2009

The Tradeoffs

The practice of medicine comes with tradeoffs. Most of risks associated with treatment are small, usually inconsequential and obvious during or immediately after the treatment is given. Cancer results from damage to genes involved in growth and regulation of cells. Growth regulatory systems have multiple damage control and backup pathways. The regulatory systems fail only after multiple hits. Years of exposure is required to carcinogens is needed to cause enough DNA damage for a cancer to emerge. Unlike other drug toxicity, the carcinogenic potential of a therapy may take years to manifest. The same can be said about heart disease which along with cancer is responsible for the largest disease burden in an ageing population.

I had earlier written about the protective effect of bisphosphonates in breast cancer. Within few years of introduction of oral bisphosphonates for the therapy of osteoporosis, it became clear that these agents carried a risk of oesophagitis and oesophageal perforation. About a decade later a concern about the association of oesophageal cancer emerged. A recently published study (BMJ 341:4444c; 2010) has concluded that the use of oral bisphosphonates increases the risk of oesophageal cancer. The study found that one (or more) prescription for oral bisphosphonates increased the risk of oesophageal cancer by 30%. Ten or more prescriptions nearly doubled the risk. Using the same database another study, with a shorter follow up, (JAMA304:657-63;2010) had failed to show an increased risk. Selective oestrogen receptor modifiers (tamoxifen and raloxifene) are used to treat osteoporosis and are effective in and under evaluation for chemoprevention of breast cancer. Tamoxifen increases the risk of endometrial cancer. Both increase the risk of thrombosis.

This is not the first time a therapy has been implicated in a serious adverse effect after years of use and this will not be the last. Intervention in chronic disease improves the health of ageing population. A chronic disease also provides a large market for the pharmaceutical industry. It is for the medical community to recognize that there are tradeoffs in medical practice. As we treat an aging population the need becomes more acute.