Localized amyloidosis carries low risk of progression to systemic disease

Last Updated: 2015-05-22

By Larry Hand

NEW YORK (Reuters Health) - The prognosis for patients with localized amyloidosis appears to be good for long-term survival, but patients still need to be assessed and monitored for the more dangerous systemic amyloidosis, UK researchers report.

"Clinicians need to be aware that localized deposits of amyloid are a rare differential diagnosis of a lump or tumor at any site. This is particularly true in cases of very slow-growing lumps," Dr. Ashutosh D. Wechalekar, of the National Amyloidosis Centre in London told Reuters Health by email. "All patients with amyloid deposits at any single site must be assessed for systemic deposits, and cardiac, renal, and liver deposits must be ruled out by simple tests."

"Without undertaking detailed assessment for systemic amyloidosis, there is a risk that some patients may be missed and develop irreversible organ failure," he added.

Dr. Wechalekar and colleagues analyzed data on 606 patients with biopsy-proven localized amyloidosis who were diagnosed, assessed and followed at their center between January 2, 1980, and December 15, 2011. Their findings were published online May 7 in The Lancet Haematology.

Patients, 51% men, had a median age of 59.5 years and a median symptom duration of seven months before diagnosis. The most common localized amyloid deposit sites were bladder (16%), laryngeal or tonsillar (15%), cutaneous (14%) and pulmonary nodular (8%), and 121 (20%) had monoclonal immunoglobulin or abnormal free light chains.

Nine patients (11%) had more than one localized cutaneous amyloid deposits and two (6%) had more than one gastrointestinal tract deposits.

Of the 606 patients, 67 (11%) also had autoimmune disorders, including Sjogren's syndrome, hypothyroidism, rheumatoid arthritis, and systemic lupus erythematosus.

After a median follow-up of 74.4 months, only seven (1%) had progressed to systemic immunoglobulin light-chain amyloidosis, and 264 (44%) had progression only at the local site. Of the seven who progressed to systemic disease, five had started in the lymph node, one started in the eyelid, and one started in bone.

Of the 94 deaths during follow-up, clinicians attributed three to progression to systemic disease.

The researchers estimated the five-year overall survival rate for the patients to be 90.6% and the 10-year survival rate to be 80.3%.

"We describe the largest reported cohort of patients with localized immunoglobin light-chain amyloidosis, confirming that the clinical features and prognosis in localized amyloidosis is remarkably good, and very different from systemic light-chain amyloidosis," the researchers write.

Asked what clinicians should tell their patients based on these results, Dr. Wechalekar said, "They need to reassure their patients with localized amyloidosis that this is very different from the very serious disease of systemic amyloidosis. This condition will not impact their survival. However, they need to keep the condition under regular monitoring as the local lumps of amyloid may increase slowly over many years and may need removal if they are causing symptoms or problems."

He offered specific suggestions: "They should alert their pathologists about this possibility and arrange for appropriate staining of the biopsies. The pathologists must refer such biopsies for specialist immunohistochemistry or mass spectrometry for amyloid typing. All such biopsies must also be reviewed by a hematopathologist to assess for presence of malignant plasma cells or low-grade lymphoma, which may occasionally be a part of this disease and need specific treatment."

Dr. Christoph Rocken, of Christian-Albrechts-University in Kiel, Germany, who wrote an accompanying editorial, told Reuters Health by email, "The clinicians should inform their patients that a thorough work-up is needed to classify amyloidosis as either localized or systemic, as this has major implications on treatment and outcome. Systemic amyloidosis is a serious disease and may necessitate a systemic treatment, which could include bone-marrow transplantation and chemotherapy."

Specifically, he added, clinicians should "confirm the diagnosis histologically including proper classification of the amyloid protein deposited . . . Clinicians (particularly general practitioners) should seek expert advice. We have a couple of Amyloidosis Centers in Europe with specialists to help colleagues. They may also serve as referral centers."

He concluded, "Based on this study we should start to design international prospective studies for the treatment of localized amyloidosis. The data presented . . . provides an excellent basis for that."

The authors reported no funding or disclosures.

SOURCE: http://bit.ly/1FowDNq and http://bit.ly/1ScLkIQ

Lancet Haematol 2015.