Category Archives: Brain SOLs

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

Mediastinal Adenopathy with Brain lesions

A 26 year old male patient presented with fever of five days duration. The complete haemogram showed a haemoglobin of 13.2g/dL, WBC count of 13500/mm3 with a differential count of 75% polymorphs, 21% lymphocytes, 2% eosinophils and 2% monocytes and a platelet count of 232,000/mm3. The smear did not show plasmodium and the serology for dengue and HIV was negative. The liver and kidney functions and the X-ray Chest was normal.

A CT scan of the chest was performed which showed mediastinal adenopathy which showed patchy enhancement on injection of contrast. The site was deemed as inaccessible for a biopsy

The patient was initiated on four drug anti-tuberculous therapy. The fever subsided in a week.

About two weeks after discharge the patient has a left sided seizure with unconsciousness. He was admitted to the hospital anti-convulsants given and an MRI of the brain preformed.

The MRI showed multiple ring enhancing lesions in the bilateral fronto-parietal temporal lobes with significant peri-lesional oedema and a significant midline structures to the left due to the right frontoparafalcine lesion.

Lymphoma is a highly curable tumour that mimics tuberculous lymphadenitis. Delay in treatment of high grade lymphomas compromises the chance of cure. Lymph node biopsy is an invasive procedure sometimes needing laparotomies and thoracotomies. The issues that arise when a lymph node is relatively inaccessible are:

Is biopsy needed for all patients with lymphadenopathies?

Patients with lymphadenopathy and an infective/inflammatory pathology in the drained areas need not be biopsied. Patients with inflamed nodes need not be biopsied. Patients with deep seated nodes in whom a certain diagnosis can be made by non-invasive tests need not be biopsied. All other patients should be biopsied. FNAC, unless it yields a specific diagnosis, is an inadequate investigation for lymphadenopathy. An excision biopsy is ideal. A large wedge biopsy is acceptable for large nodes and a trucut biopsy is appropriate for deep seated nodes. Many patients have succumbed to an advanced lymphoma because of delayed diagnosis from an inappropriate or inadequate biopsy. From the pathologists point of view the diagnosis of lymphoma may be one of the most challenging. Not everyone is experienced enough to make the diagnosis. Even the experienced pathologists can only report on the material provided. Providing appropriate material is the responsibility of the clinician. When one is treating on a clinical diagnosis the patients needs a close monitoring for signs of treatment failure and an alternative diagnosis.

Is there a blood test for the diagnosis of lymphomas?

Lymphomas are of two types Hodgkin’s and non-Hodgkin. Non-Hodgkin’s lymphoma is a collection of about 30 distinct malignancies of the lymphoid cells. Non-Hodgkin’s lymphomas have a leukaemic phase i.e. the phase when the malignant cells spill into the blood. Leukaemic phase occurs early in the course of the disease in patients with low grade lymphomas e.g. small lymphocytic lymphoma, follicular lymphomas and splenic marginal zone lymphomas and very high grade lymphomas e.g. Burkitt’s lymphoma and lymphoblastic lymphoma. The leukaemic phase of small lymphocytic lymphoma is chronic lymphocytic leukaemia and that of very high grade lymphomas is acute lymphoblastic leukaemia. Blood tests can only diagnose lymphomas which are in the leukaemic phase. There are no other blood tests for the diagnosis of lymphomas

Does an MRI scan differentiate a lymphoma from tuberculosis?

A tuberculous granuloma caseates resulting in ring enhancement and oedema around the lesion. The other ring enhancing lesions include primary brain tumour (glioblastoma), metastasis (especially post chemotherapy), abscess, Toxoplasma and Cryptococcus in HIV, resolving hematoma (10-21 days), radiation necrosis, and aneurysm. The MRI features of a primary CNS lymphoma in an immune competent host are quite distinct. The tumour is isointense on T1 and show pronounced uniform enhancement and very little peri-lesional oedema. Ring enhancement is seen rarely. In immunocompromised patients ring enhancement, multiple lesions, spontaneous haemorrhage and non-enhancing lesions are common making it difficult to distinguish CNS lymphoma from infections in these patients. A patient with high index of suspicion of lymphoma must undergo a biopsy.

Could these CNS lesions be from a lymphoma?

The MRI picture is inconsistent with a lymphoma in an immune competent patient. Synchronous CNS and systemic lymphomas are very rare and have been reported only in immunocompromised patients. One report of AIDS related lymphomas described synchronous CNS involvement in 5/19 patients (Annals of Oncology 18 (Supplement 9): ix178–ix182, 2007, abstract 71). Synchronous CNS involvement has also been described in a child with immunodeficiency J Pediatr Hematol Oncol. 2008 Apr;30(4):317-9. Isolated CNS relapse from a lymphoma is seen in less than 1% of the patients. This patient was treated as tuberculosis.