Case of the Month: March 2023
posted: March 27, 2023
A 68-year-old Black woman with h/o stable pulmonary nodules, intermittent right eye scleritis, bilateral parotid swelling, and elevated serum angiotensin converting enzyme and lysozyme presented with new onset fatigue, back pain, and weight loss. New labs revealed abnormal LFTs (elevated alkaline phosphatase and gamma-glutamyl transpeptidase with normal bilirubin and serum aminotransferases). Autoimmune and infectious serologies were negative. MRI abdomen showed mild hepatomegaly and heterogeneous enhancement of liver parenchyma. A liver biopsy was performed with concern for sarcoidosis of the liver.
Final Diagnosis: Amyloidosis Involving Hepatic Sinusoids and Vessels of the Portal Tract
Biopsy findings prompted hematologic evaluation. IgG lambda monoclonal protein was identified on SPEP and immunofixation. Mass spectrometry on the liver biopsy revealed an AL (lambda) type amyloid. The patient underwent a bone marrow biopsy that revealed a lambda restricted plasma cell clone.
- AL (primary) amyloidosis is the most common type of systemic amyloidosis (incidence: 12 cases per million persons per year). While hepatic involvement is common in AL amyloidosis, it is seldom first diagnosed on liver biopsy. Organ involvement in AL amyloidosis in order of decreasing frequency: heart (75%), kidney (57%), nerves (22%), and liver (20%).
- Clinical presentation of hepatic amyloidosis may include hepatomegaly, cholestasis, portal hypertension, ascites, and rarely liver failure.
- Amyloidosis imparts a waxy or “lardaceous” gross appearance. Histologically, hepatic amyloidosis is characterized by extracellular deposition of acellular pale pink material within sinusoidal space, arterial wall, and portal tract with atrophy of hepatocytes. Findings can be subtle. Deposits are Congophilic and show “apple green” birefringence under polarized light. Amyloid deposits by electron microscopy (EM) show characteristic randomly oriented fibrils (~ 10 nm thick). Mass spectrometry is the gold standard for typing amyloid.
- “Amyloid-like” deposits are seen in the rare monoclonal immunoglobulin deposition disease (MIDD). However, these deposits are Congo Red negative and are not fibrillar by EM. The light chains deposited are overwhelmingly kappa in MIDD and lambda in AL amyloidosis.
- Treatment of AL amyloidosis focuses on eradication of neoplastic plasma cell clone. Early diagnosis is vital for effective therapy and survival.
- Gertz MA, Dispenzieri A. Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review. JAMA. 2020;324(1):79–89. doi:10.1001/jama.2020.5493
- Wang YD, Zhao CY, Yin HZ. Primary hepatic amyloidosis: a mini literature review and five cases report. Ann Hepatol. 2012 Sep-Oct;11(5):721-7. PMID: 22947537.
This case is contributed by Geetha Jagannathan, MD, Vaidehi Avadhani, MD and Marina Mosunjac, MD. Department of Pathology and Laboratory Medicine, Grady Memorial Hospital, Emory School of Medicine.