Amyloidosis is a slowly progressive disease which can lead to significant morbidity and death. Amyloid deposits are extracellular and not metabolized or cleared by the body. Thus, the progressive deposits eventually impair the function of the organs where they accumulate. Amyloid is derived from precursor proteins that either have an abnormal structure or are abnormally increased in the serum. About 18 different amyloid precursor proteins have been described.
AMYLOID PROTEIN DESIGNATION Immunoglobulin light chain AL Immunoglobulin heavy chain AH Serum amyloid A protein AA Transthyretin ATTR beta-2-microglobulin Abeta2M Apolipoprotein A-I AApoA1 Lysozyme ALys Atrial natriuretic factor AANF Insulin AIns
Localized deposits of amyloid may occur in various organs. Probably the most significant finding is the discovery of amyloid in patients with Alzheimer's disease. In this setting, amyloid is postulated to have neurotoxic properties. The definitive diagnosis of amyloidosis is made by histological examination of a biopsy specimen.
Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
DISEASE ASSOCIATIONS CHARACTERIZATION ALOPECIA Progressive generalized alopecia due to systemic amyloidosis
Michael E. Lutz, MD
Mark R. Pittelkow, MD
J Am Acad Dermatol 2002;46:434-6 Abstract quote
We describe the case of a patient with systemic amyloidosis that manifested as generalized alopecia. Amyloidosis was documented by means of skin biopsy and urine immunoelectrophoresis.
ALZHEIMER'S DISEASE HEME OXYGENASE-1 DEFICIENCY
Heme oxygenase–1 deficiency: The first autopsy case
Atsuhiro Kawashima, MD, PhD
Yoshio Oda, MD
Akihiro Yachie, MD
Shoichi Koizumi, MD
Isao Nakanishi, MD
Hum Pathol 2002;33:125-130. Abstract quote
This article describes the first autopsy case of heme oxygenase (HO)-1 deficiency.
A 6-year-old boy who presented with growth retardation; anemia; leukocytosis; thrombocytosis; coagulation abnormality; elevated levels of haptoglobin, ferritin, and heme in serum; a low serum bilirubin concentration; and hyperlipidemia was diagnosed as HO-1 deficient by gene analysis several months before death.
Autopsy showed amyloid deposits in the liver and adrenal glands and mesangioproliferative glomerular changes in kidneys, in addition to an irregular distribution of foamy macrophages with iron pigments. Fatty streaks and fibrous plaques were noted in the aorta. Compared with HO-1–targeted mice, the present case seems to more severely involve endothelial cells and the reticuloendothelial system, resulting in intravascular hemolysis, disseminated intravascular coagulation, and amyloidosis with a short survival.
This contrasts to the predominant iron metabolic disorders of HO-1–targeted mice with a long survival.
Bullous amyloidosis: the mechanism of blister formation revealed by electron microscopy
Toyoko Ochiai, Takafumi Morishima, Takako Hao and Atsuko Takayama
Department of Dermatology, Nihon University, School of Medicine, Tokyo, Japan
Journal of Cutaneous Pathology 2001;28 (8), 407-411 Abstract quote
Background: Few electron microscopic studies of blister lesions in bullous amyloidosis have been reported, and the mechanism of blister formation remains to be elucidated. This study was designed to examine the nature of bullous amyloidosis ultrastructurally, and clarify the pathogenesis of blister formation.
Methods: We examined a 47-year-old woman with IgD-lambda type myeloma, suffering from bullous lesions on her hands and feet caused by trauma or rubbing. Light and electron microscopic studies were performed.
Result: Ultrastructurally, amyloid deposits aggregated under the lamina densa. Keratinocyte protrusions penetrated the dermis through the gap in the lamina densa and enfolded amyloid deposits. Amyloid globules were found in enlarged intercellular spaces of keratinocytes. Desmosomes were sparsely distributed in some areas of the epidermis.
Conclusion: These results indicate that keratinocytes enfold the amyloid globules and take them in the intercellular space of epidermis, and that the breakdown of the lamina densa and widening of the intercellular space between keratinocytes induce skin fragility. Trauma or rubbing of her hands and feet appears to act as the localized precipitating factor of blister formation in bullous amyloidosis.
CHARACTERIZATION Radiographs CT scan and MRI Laboratory Markers Biochemical Subtyping of Amyloid in Formalin-Fixed Tissue Samples Confirms and Supplements Immunohistologic Data
Am J Clin Pathol 2004;121:794-800 Abstract quote
The systemic amyloidoses are a heterogeneous group of congophilic fibrillar protein deposition diseases that should be subtyped chemically by immunohistologic methods. Biochemical methods sometimes are required to confirm or identify the amyloid type in unfixed or in formalin-fixed tissue samples.
We report the results of formic acid extraction and immunochemical and biochemical characterization of deposits in formalin-fixed tissue samples from 10 cases of amyloidosis and 3 from nonamyloid monoclonal immunoglobulin light chain deposition disease. The results in 11 of 13 cases demonstrated concordance with the previous immunohistochemical and/or biochemical data obtained in unfixed tissue samples from the same specimens, and in 2 of 13, the protein deposits that previously could not be classified by standard immunohistochemical methods were identified by amino acid sequence.
An additional new finding of constant-region rather than variable-region fragments as the major constituent protein in 1 case of l light chain amyloidosis demonstrated the value of the method and its importance for future applications.
Chemical Typing of Amyloid Protein Contained in Formalin-Fixed Paraffin-Embedded Biopsy Specimens
Charles L. Murphy, MS, Manfred Eulitz, MD, Rudi Hrncic, MD, Knut Sletten, PhD,Per Westermark, MD, PhD,Teresa Williams, Sallie D. Macy, MT, Craig Wooliver, MT, Jonathan Wall, PhD, Deborah T. Weiss, and Alan Solomon, MD
Am J Clin Pathol 2001;116:135-142 Abstract
The human amyloidoses represent a heterogeneous group of disorders characterized by the deposition of fibrillar protein in vital organs. Given the fact that at least 20 different molecules can form fibrils, the unambiguous identification of the type of amyloid deposited is critical to the correct diagnosis and treatment of patients with these disorders. Heretofore, this information has been inferred from particular clinical features of the disease, ancillary laboratory tests, and results of immunohistochemical analyses. However, to establish unequivocally the kind of protein that is deposited as amyloid, it is necessary to determine its chemical composition through amino acid sequencing or mass spectroscopy of material extracted from fibrillar deposits.
We have developed a micromethod whereby such studies can be performed readily using sections of formalin-fixed, paraffin-embedded biopsy specimens. The ability to identify precisely the nature of the tissue deposits has diagnostic, therapeutic, and prognostic implications for patients with amyloid-associated disorders.
SERUM LIGHT CHAINS
Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis.
Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, Kyle RA, Gertz MA.
Division of Clinical Biochemistry and Immunology, University of Birmingham, Birmingham, England.
Am J Clin Pathol 2003 Feb;119(2):274-8 Abstract quote
Primary systemic amyloidosis is a plasma cell dyscrasia characterized by the accumulation of excess free immunoglobulin light chains (FLCs) as amyloid. One of the diagnostic features of amyloidosis is the presence of circulating monoclonal FLCs in the serum and urine of the patients.
The FLC usually is present in small amounts, and immunofixation is required for detection. A nephelometric method for quantitating FLCs in serum has been described using antibodies that recognize only FLC not bound to heavy chain.
We describe a retrospective study using this quantitative FLC method for assessing monoclonal FLCs in 95 patients with amyloidosis. The sensitivity of nephelometric serum FLC measurements is particularly useful in patients with negative immunofixation results for serum, urine, or both.
In addition, the FLC assay can be used for follow-up of patients with amyloidosis who have undergone stem cell transplantation.
CHARACTERIZATION General VARIANTS BONE MARROW Bone Marrow Core Biopsy Specimens in AL (Primary) Amyloidosis A Morphologic and Immunohistochemical Study of 100 Cases
Niall Swan, MD, Martha Skinner, MD, and Carl J. O'Hara, MD
Am J Clin Pathol 2003;120:610-616 Abstract quote
We retrospectively reviewed 100 bone marrow core biopsy specimens from patients with AL (primary) amyloidosis. The morphologic and immunohisto-chemical features were assessed by standard histochemical stains (H&E, periodic acid–Schiff, Congo red) and immunohistochemical stains for light chain immunoglobulins. Bone marrow core biopsy revealed a plasma cell dyscrasia in 83% ( l , 65; k , 18) of cases.
Amyloid deposits were observed in 60% of the bone marrow core biopsy specimens and, when present, were detected most often in blood vessel walls only (39/60). However, if present, interstitial amyloid deposition was significantly more associated with patients with a monoclonal k light chain gammopathy ( P = .04).
Through the careful analysis of standard histochemical and immunohistochemical stains, bone marrow core biopsy provides essential diagnostic information in cases of AL amyloidosis.
- Primary localized laryngeal amyloidosis: report of 3 cases with long-term follow-up and review of the literature.
Ma L, Bandarchi B, Sasaki C, Levine S, Choi Y.
Department of Pathology, Yale University School of Medicine, New Haven, CN, USA.
Arch Pathol Lab Med. 2005 Feb;129(2):215-8. Abstract quote
CONTEXT: Localized laryngeal amyloidosis is an uncommon condition with limited long-term follow-up studies. The precise etiology and pathogenesis are not entirely clear.
OBJECTIVE: To further characterize the histopathologic features and possible pathogenesis of localized laryngeal amyloidosis.
DESIGN: Three cases of primary localized laryngeal amyloidosis were identified at our institutions from 1980 to 2003. The clinical features and histologic and immunohistochemical patterns were evaluated. Systemic workups were pursued during the long-term follow-up.
RESULTS: The common presentation of the patients was hoarseness. The lesions involved vocal cords, anterior commissure, and ventricle. Microscopically, the amyloid was present within the submucosa with an adjacent lymphoplasmacytic infiltrate. The plasma cells and amyloid demonstrated monoclonal light chain restriction in all 3 cases (2 lambda, 1 kappa). No evidence of systemic amyloidosis or an overt B-cell lymphoma was found in these patients. Two patients with long-term follow-up underwent subsequent surgical removals for multiple recurrences, which occurred within 1 year of the initial diagnosis.
CONCLUSIONS: The demonstration of monoclonal light chain expression in the plasmacytic infiltrate and amyloid component in the absence of systemic lymphomas indicates that localized laryngeal amyloidosis may represent a form of benign monoclonal plasma cell dyscrasia. A close follow-up of the patients may be indicated for early detection of recurrences.
- Globular hepatic amyloid: an early stage in the pathway of amyloid formation: a study of 20 new cases.
Division of Hepatic Pathology, Department of Hepatic and Gastrointestinal Pathology, and the Veterans Administration Special REFERENCE Laboratory for Pathology, Armed Forces Institute of Pathology, Washington, DC.
- Am J Surg Pathol. 2007 Oct;31(10):1615-21. Abstract quote
Only 25 cases of globular hepatic amyloidosis have been reported, mostly from the early 1980s.
We reviewed clinical, histopathologic, and immunohistochemical features of 20 cases of hepatic globular amyloid out of 208 cases of liver amyloidosis seen at the Armed Forces Institute of Pathology since 1970. Fourteen (70%) were men and 6 were women with a median age of 67 years (range, 40 to 92 y). More than half of the patients were Hispanic. Ten of 20 patients were diagnosed with systemic amyloidosis.
Histologically, all cases revealed round to oval-shaped sometimes laminated globules, 1 to 40 mum in diameter, and 6 cases had evidence of transition from globular to the more usual linear form. In all 20 cases, Congo red and/or Sirius red stained the globules red and showed an apple green birefringence under polarized light. Portal tracts and parenchyma were involved in 15/20 the cases, and sinusoidal deposition alone in 5 cases. Vascular deposition was very common with more than 3/4 of the cases showing mainly perivenular amyloid with both the terminal hepatic venules and portal vein branches being equally involved. A few intrahepatocellular globules were present in half of the cases.
In conclusion, hepatic amyloidosis can rarely occur as a globular form, and the finding of intracellular amyloid globules and transitional forms of globular to linear patterns of deposition suggest that this is an early form of hepatic involvement by systemic amyloidosis.
Hum Pathol. 2005 Jul;36(7):845-9 Abstract quote.
Hepatic amyloid deposition in the form of globular inclusions is a rare occurrence. Only 24 such cases have been reported to date. Its clinical and pathological significance are undefined. Unawareness of such a pattern can cause diagnostic confusion.
We herein describe a case of globular hepatic amyloid in a patient with a B-cell lymphoma and chronic hepatitis C. The findings in our case support the literature data in that (1) it is often an incidental finding during workup for other coexisting conditions and (2) its morphology is peculiar but can be recognized with ease if one is aware of its existence.
Our case also provides new insights into this condition. First, it represents the first nonautopsy case to demonstrate that globular hepatic amyloid is an indication of systemic amyloidosis, thus emphasizing the clinical importance of the recognition of this condition. Second, in our case, there was a coexisting B-cell lymphoma, the constituent cells of which showed immunoglobulin lambda light chain restriction, and patient's serum lambda light chain was elevated. However, light chain restriction was not demonstrated in the globular inclusions, and there was no evidence of monoclonal gammopathy by serum electrophoresis. Whether immunoglobulin light-chain abnormality played a causal role in this condition is to be determined.
LUNGS Amyloid-like Pulmonary Nodules, Including Localized Light-Chain Deposition Clinicopathologic Analysis of Three Cases
Andras Khoor, MD, Jeffrey L. Myers, MD, Henry D. Tazelaar, MD, and Paul J. Kurtin, MD
Am J Clin Pathol 2004;121:200-204 Abstract quote
Amyloid-like pulmonary nodules have been described in patients with systemic light-chain deposition disease, but their significance in other clinical contexts is unknown.
We examined biopsy specimens of amyloid-like pulmonary nodules from 3 women without systemic light-chain deposition disease. Patient 1 (aged 62 years) had multiple pulmonary nodules and underwent 2 separate lung biopsies, the first showing nodules composed of k light-chain deposits accompanied by low-grade lymphoplasmacytic lymphoma limited to the lung and the second, obtained after chemotherapy 9 months later, showing only residual nodules without persistent lymphoma. Patients 2 (aged 65 years) and 3 (aged 69 years) had asymptomatic solitary pulmonary nodules. In all cases, electron microscopic examination showed dense granular extracellular deposits without the fibrillary characteristics of amyloid.
Amyloid-like nodules should be distinguished from nodular amyloidosis and, in some patients, might represent a localized form of light-chain deposition.
Beta-2 Microglobulin Amyloidosis Presenting as Bilateral Ovarian Masses A Case Report and Review of the Literature
Sharon L. Mount, M.D. ; Gamal H. Eltabbakh, M.D. ; Nicholas J. Hardin, M.D.
From the Division of Anatomic Pathology, Department of Pathology (S.L.M., N.J.H.), and the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology (G.H.E.), University of Vermont/Fletcher Allen Health Care, Burlington, Vermont, U.S.A.
Am J Surg Pathol 2002;26:130-133 Abstract quote
We report a case of systemic beta-2 microglobulin amyloidosis (B2M) in which the initial clinical presentation was that of bilateral ovarian masses.
A 56-year-old woman who had been on renal dialysis for 12 years because of familial glomerulonephritis underwent a total hysterectomy and bilateral salpingo-oophorectomy for suspected ovarian malignancy. Pathologic findings included extensive amyloid infiltration of both ovaries, fallopian tubes, and focal perivascular deposition in the myometrium. The diagnosis of amyloidosis was confirmed with Congo red stain, B2M immunohistochemistry, and electron microscopy. Systemic amyloidosis in renal dialysis patients commonly presents as bone and/or joint disease, although visceral involvement has been reported.
This is the first report in the English language literature to describe amyloidosis presenting as bilateral ovarian masses.
Localized amyloidosis of the glans penis: a case report and literature review.
Ritter M, Nawab RA, Tannenbaum M, Hakky SI, Morgan MB.
Department of Pathology, University of South Florida, Tampa, FL; Departments of Pathology and Urology, Bay Pines Veteran's Hospital, Bay Pines, FL; and Department of Pathology, James Haley Veteran's Hospital, Tampa, FL USA.
J Cutan Pathol 2003 Jan;30(1):37-40 Abstract quote
BACKGROUND: Primary localized cutaneous amyloidosis is an uncommon lesion with a varied pathogenesis.
METHODS: We report the case of a 67-year-old-male discovered to have a localized amyloid lesion of the glans penis.
RESULTS: Biopsy of the lesion revealed dermal deposits of amorphous eosinophilic material which stained positive with Congo red and amyloid P protein. Additional stains, including kappa and lambda light chains, amyloid A, and transthyretin, were negative. The lesion has remained asymptomatic, with no evidence of systemic disease identified, and no further treatment has been necessary.
CONCLUSIONS: This is the sixth reported case of localized amyloidosis of the glans penis. Based on the clinical behavior and pathologic characteristics, this type of lesion is best classified as primary localized cutaneous amyloidosis, in the same family as the macular/lichenoid type lesions.
Pleural amyloidosis mimicking mesothelioma: A clinicopathologic study of two cases
Amy L. Adams, MD
Claudia Y. Castro, MD
Satinder P. Singh, MD
Cesar A. Moran, MD
From the Departments of Pathology and Radiology, The University of Alabama at Birmingham, AL.
Ann Diagn Pathol 5: 229-232, 2001. Abstract quote
Two cases of pleural amyloidosis are presented. The patients are two men, 70 and 72 years of age respectively. Neither patient had evidence of systemic amyloidosis. Each presented clinically with symptoms of chest pain and dyspnea. Radiologically, both patients showed diffuse pleural thickening similar to that observed in malignant mesothelioma. In both patients, surgical decortication of the pleura was performed.
Histologically, the lesions were characterized by the presence of an amorphous eosinophilic material with focal collections of a lymphoplasmacytic infiltrate. Focal clusters of giant cells were admixed with the lymphoplasmacytic infiltrate. Histochemical stains for Congo red showed strong positive apple-green birefringency. Immunohistochemical studies using kappa and lambda light chains showed polyclonality. The cases discussed herein represent an unusual presentation of amyloid and one that needs to be considered in the differential diagnosis of malignant mesothelioma.
Nodular amyloidosis: review and long-term f-up of 16 cases.
Moon AO, Calamia KT, Walsh JS.
Mayo Clinic, Jacksonville, FL 32224, USA.
Arch Dermatol. 2003 Sep;139(9):1157-9. Abstract quote
OBJECTIVES: To review the clinical presentations of nodular amyloidosis, examine these cases for evidence of plasma cell monoclonality, and obtain long-term follow-up data on progression to systemic amyloidosis.
DESIGN: Retrospective case series with long-term follow-up data obtained by phone survey.
SETTING: Mayo Clinic, Rochester, Minn, and Mayo Clinic, Jacksonville, Fla.
PATIENTS: All patients diagnosed with nodular amyloidosis between 1971 and 2001.
MAIN OUTCOME MEASURES: Clinical records and histopathologic characteristics were reviewed. Polymerase chain reaction to assess immunoglobulin gene rearrangement and immunohistochemical analysis to detect kappa and lambda light chain restriction were performed on paraffin-embedded specimens. Patients were contacted by phone to determine if progression to systemic disease had occurred.
RESULTS: We identified 16 patients with nodular amyloidosis. Mean age at diagnosis was 60.8 years (range, 41-87 years). Eight (50%) of 16 patients had acral involvement. Immunohistochemical analysis demonstrated light chain restriction in 6 of 10 patients. At the time of diagnosis, no patient was known to have systemic amyloidosis. One patient, however, had a serum monoclonal lambda protein and died 4 years later secondary to systemic amyloidosis. Follow-up data were obtained in 14 of the remaining 15 patients, with a mean follow-up time of 10 years (range, 8 months to 24 years). None of the 14 patients had signs or symptoms suggesting progression to systemic amyloidosis.
CONCLUSIONS: Nodular amyloidosis affects both sexes during middle age, with a tendency to affect acral sites. The relatively high rate of light chain restriction in our series provides further evidence for the presence of a local plasma cell clone. Progression to systemic amyloidosis is uncommon.
Case Studies Subcutaneous nodular amyloidosis: A case report and review of the literature
Tracy U. Nguyen, etal.
HUM PATHOL 32:346-348. (Abstract quote)
Amyloidosis typically manifests with disseminated infiltration of multiple organ systems. Rarely, amyloidosis may be localized.
We report a patient with localized subcutaneous nodular amyloidosis, without systemic amyloid involvement or myeloma, whose presenting symptom was multiple discrete neck nodules. Immunohistochemical analysis showed the amyloid deposits to be derived from lambda light chains. Twenty-four month follow-up showed minimal disease progression. A literature review showed only 5 reported cases of subcutaneous nodular amyloidosis.
This is the first description of a patient with subcutaneous nodular amyloidosis derived from lambda light chains.
- Am J Surg Pathol. 2007 Jan;31(1):141-145. Abstract quote
We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis producing rare endoscopic and histologic findings. The patient had no specific gastrointestinal complaints but underwent esophagogastroduodenoscopy and colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple polyps, some filiform and measuring up to 3 cm in length, in the duodenum and proximal jejunum.
Microscopically, the polyps resulted from amyloid deposition, predominantly within the submucosa, but also focally involving muscularis mucosae and lamina propria. The amyloid formed multiple globular submucosal deposits with a lamellated appearance reminiscent of corpora amylacea; linear amyloid deposition was also present in a perivascular distribution and within the overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda immunoglobulin light chain restriction. There was no clinical evidence of visceral amyloidosis. The source of lambda light chain production was unclear as bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was normal, as were serum and urine protein electrophoreses with immunofixation.
This endoscopic presentation of isolated small bowel polyposis is an uncommon association with AL amyloidosis and to our knowledge this represents the first case of globular gastrointestinal amyloidosis resulting from AL amyloid.
SOFT TISSUE Soft tissue amyloidoma of the extremities: a case report and review of the literature.
Bardin RL, Barnes CE, Stanton CA, Geisinger KR.
Department of Pathology, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157-1072, USA.
Arch Pathol Lab Med. 2004 Nov;128(11):1270-3. Abstract quote
The deposition of amyloid as a distinct, clinically apparent mass is uncommon, particularly in soft tissues. Among reported sites of soft tissue amyloidomas, the extremities are quite rare. Amyloid tumors can mimic malignant neoplasms both clinically and radiologically.
We report a case of AA amyloidoma presenting in the deltoid region with radiological features suggesting sarcoma. Cytomorphology from fine-needle aspiration material, tissue histology, and appearance by magnetic resonance imaging are described. The literature on soft tissue amyloidoma is reviewed.
Soft Tissue Amyloidoma With Features of Plasmacytoma.
Yin H, Alhasan; N, Ciervo A, Zinterhofer L.
Department of Pathology (Drs Yin and Zinterhofer) and Department of Vascular Surgery (Dr Ciervo), Monmouth Medical Center, Long Branch, NJ; and Medical College of Pennsylvania, Philadelphia (Mr Alhasan).
Arch Pathol Lab Med 2002 Aug;126(8):969-971 Abstract quote
Soft tissue amyloidoma is rare, and soft tissue amyloidoma associated with plasmacytoma and without evidence of systemic amyloidosis is even more rare.
We report a case of soft tissue amyloidoma associated with an apparently localized monoclonal proliferation of plasma cells (plasmacytoma).
HISTOPATHOLOGY CHARACTERIZATION GENERAL Hyalinized acellular stroma, usually perivascular accentuation
Am J Surg Pathol. 2006 Jun;30(6):673-683. Abstract quote
We aimed to reassess the suitability of immunohistochemical classification of amyloid in surgical pathology.
One hundred sixty-nine biopsies from 121 patients diagnosed with amyloid during the period from 1994 to 2004 were included. Amyloid was classified immunohistochemically, using antibodies directed against amyloid P-component, AA amyloid, apolipoprotein AI, fibrinogen, keratoepithelin, lactoferrin, lysozyme, beta2-microglobulin (beta2M), immunoglobulin-derived lambda-light and kappa-light chains, and transthyretin.
Amyloid was most commonly present in biopsies from the hepatogastrointestinal tract. The deposits were classified immunohistochemically in 156 (92%) biopsies. In 13 biopsies of 12 patients, amyloid remained unclassified. AL amyloidosis was diagnosed in 76 (45%) biopsies and was further categorized into AL amyloid of kappa-light chain origin [32 (42%) biopsies] or lambda-light chain origin [20 (26%)]. In 24 (32%) biopsies, the amyloid deposits did not show unequivocal staining for lambda-light or kappa-light chain. However, these cases were categorized as "probably AL amyloid, not otherwise specified", because no other antibody showed unequivocal staining of the amyloid deposits. AA amyloidosis was diagnosed in 32, ATTR amyloidosis in 21, and AApoAI amyloidosis in 3 biopsies. Other types of amyloid included AKer and ALac amyloids each in 1, and ALys and ACal amyloids each in 2 biopsies. Abeta2M amyloid was not diagnosed in any case.
Immunohistochemical classification of amyloid still poses problems. Although classification of AA, AApoAI, ALys, ALac, and ATTR amyloids is relatively straightforward, classification of AL amyloid and rare hereditary amyloidoses is a serious obstacle and sometimes even impossible when conclusive clinical information or additional protein biochemical or molecular biologic studies are not available.
An immunohistochemical study of cytokeratins in skin-limited amyloidosis.
Inoue K, Takahashi M, Hamamoto Y, Muto M, Ishihara T.
Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan.
Amyloid 2000 Dec;7(4):259-65 Abstract quote
The frequency of amyloid deposits in cases of seborrheic keratosis was investigated In addition, the origin of amyloid protein(s) in lichen amyloidosis, macular amyloidosis and seborrheic keratosis was studied by immunohistochemical staining using a panel of anti-cytokeratin (CK) monoclonal antibodies.
Amyloid deposits were found in 41 of 327 specimens (12.5%) from 301 cases of seborrheic keratosis. Amyloid deposits in seborrheic keratosis reacted with 6 of 12 CK antibodies and in lichen and macular amyloidosis (20 specimens) reacted with 5 of 12 CK antibodies. In seborrheic keratosis, antibody DE-K10 (labeling CK10) reacted with amyloid in 17 of 36 cases, antibody 34betaE12 (labeling CK1, 5, 10, 14) reacted in 33 of 39 cases, and antibody MNF116 (labeling CK5, 6, 8, 17) reacted in 32 of 35 cases. Among 20 specimens from lichen and macular amyloidosis, the three antibodies reacted with amyloid in the following rates: 1 with antibody DE-K10, all 20 with antibody 34betaE12, and 6 with antibody MNF116.
These results suggest that amyloid deposits in seborrheic keratosis and lichen and macular amyloidosis may derive from epidermal cytokeratins.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION ACRAL KERATOSIS WITH EOSINOPHILIC DEPOSITS
- J Cutan Pathol. 2006 Oct;33(10):679-85 Abstract quote
Aims: The differential diagnosis of acral keratoses is broad. Encompassing a variety of infectious, heritable and degenerative disorders, emphasis upon the clinical setting and histologic subtlety are often required to arrive at the correct diagnosis. Herein, we report on a series of adult patients who presented with agminated or solitary papules of the distal finger found on histologic examination to contain amorphous eosinophilic deposits.
Results: The eosinophilic deposits were found in close proximity to the overlying epithelium and devoid of apoptotic keratinocytes, plasma cells, or vascular thickening reminiscent of amyloidosis or hyalinosis cutis. Special and immunostains yielded eosinophilic material that was elastin and Protein P negative. Despite a similar histomorphologic appearance to colloid milium, typical clinical features of this entity were not present.
Conclusion: The etiologic significance of this condition is unknown. Potential sources of the material and a discussion of the differential diagnosis follow.
Am J Clin Pathol. 2004 Aug;122(2):232-7. Abstract quote
We describe 13 cases in which the submucosa and muscularis mucosae of the gastrointestinal tract exhibited a focal or diffuse increase of elastin fibers. This elastosis or elastofibromatous change most commonly manifested as a colonic polyp and usually was found during screening colonoscopy. Gastric and small intestinal cases were less frequent and associated with ulcers or an inflammatory process. The literature includes reports of 13 gastrointestinal elastotic lesions with a topographic distribution similar to that in our series.
Histologically, elastosis appears as finely granular and/or fibrillar amphophilic material, sometimes with a fibrous component (elastofibromatous change). The changes occasionally appear centered around blood vessels and often are mistaken for amyloid but are negative for Congo red stain and strongly positive for elastin stain.
We believe that this lesion might be more underrecognized than rare. In 2 of 26 cases, elastotic lesions also were present in nongastrointestinal sites.
LIGHT CHAIN DEPOSITION DISEASE
- Pulmonary Light Chain Deposition Disease: Report of Five Cases and Review of the Literature.
*Department of Pathology at Beth Israel Deaconess Medical Center, Boston MA double daggerBethesda Naval Medical Center, Bethesda, MD daggerGeorgetown University Medical Center, Washington, DC parallelDepartment of Pulmonary and Mediastinal Pathology paragraph signDivision of Nephropathology, Armed Forces Institute of Pathology, Washington, DC section signDepartment of Pathology at Inova Fairfax Hospital, Fairfax, VA musical sharpDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
- Am J Surg Pathol. 2007 Feb;31(2):267-276. Abstract quote
Light chain deposition disease (LCDD) in the lung is a rare occurrence.
We describe 5 new cases of this entity, review the literature, and compare pulmonary light chain deposits to pulmonary amyloidosis. In addition, we identified 17 patients with pulmonary LCDD in the literature with sufficient clinical information to allow evaluation of clinical presentation, laboratory findings, histologic appearance, and disease progression. In these 22 patients, 2 different histologic patterns were appreciated: diffuse and nodular. A parallel with the diffuse and nodular forms of pulmonary amyloidosis is suggested.
The 10 patients with nodular LCDD had an overall better prognosis compared with the 12 patients with diffuse pulmonary LCDD. However, when compared to what is reported in the literature for nodular pulmonary amyloidosis, the patients with nodular LCDD had a higher incidence of an associated lymphoproliferative and/or plasma cell dyscrasia and renal failure.
Light chain deposits in the lung are histologically similar to amyloid but are not Congophilic. Their electron microscopic appearance is distinctly different with fibrils in amyloid and granular deposits in LCDD. As the diffuse forms of LCDD and amyloidosis have a similarly poor prognosis, differentiating the 2 entities is probably not critical. However, when present as nodules, LCDD is more frequently associated with an underlying plasma cell dyscrasia or renal failure than is amyloidosis, and therefore the distinction may be clinically important.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS SKIN
Nodular localized primary cutaneous amyloidosis: a long-term follow-up study.
Woollons A, Black MM.
St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Medical and Dental Schools, University of London, UK.\
Br J Dermatol 2001 Jul;145(1):105-9 Abstract quote
We present long-term follow-up data on patients with nodular localized primary cutaneous amyloidosis (NLPCA) seen at the St John's Institute of Dermatology between 1968 and 1999. This is the largest clinical follow-up study of this type of amyloid to date.
Based on these cases we estimate the rate of progression of NLPCA to systemic amyloidosis to be only 7%, much lower than the 50% rate currently quoted in the literature.
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