Unusual primary cutaneous localized amyloidosis

The case of a 41-year-old female patient with an unusual type of primary localized cutaneous amyloidosis is reported. Clinical examination revealed lesions typical for macular cutaneous amyloidosis, while histology and histochemistry, in contrast, revealed the presence of nodular amyloidosis of the skin with deposition of lambda light chain amyloid.     

Nodular cutaneous amyloidosis

A nodular cutaneous amyloidosis biopsy specimen from a solitary nodule of a 75-year-old patient was characterized by amino terminal sequence analysis and was proved to be derived from immunoglobulin kIII light chain. Five years after the diagnosis of amyloidosis in the skin was made, a rectal biopsy demonstrated amyloid deposits in a blood vessel. It is suggested that nodular cutaneous amyloidosis is a slowly progressive systemic disease of the AL type, that manifest itself mainly in the skin.     

Advanced glycation end product-modified beta2-microglobulin is a component of amyloid fibrils of primary localized cutaneous nodular amyloidosis

Primary localized cutaneous nodular amyloidosis is a rare form of cutaneous amyloidosis. Amyloid fibrils in primary localized cutaneous nodular amyloidosis have been reported to be originated from immunoglobulin light chains. Immunohistochemical studies on the lesional skins of four patients with primary localized cutaneous nodular amyloidosis demonstrated that amyloid deposits of all cases showed a positive reaction with the antibodies for beta2-microglobulin and advanced glycation end products as well as immunoglobulin light chain (kappa or lambda). No beta2-microglobulin and advanced glycation end product immunoreactivity was found in the amyloid deposits of other primary localized cutaneous amyloidosis (lichen amyloidosis and macular amyloidosis). Double immunofluorescence study of the lesional skin of primary localized cutaneous nodular amyloidosis showed that anti-kappa light chain, anti-beta2-microglobulin and anti-advanced glycation end product antibodies mostly reacted with the same area of amyloid deposit. Amyloid proteins were sequentially extracted with distilled water from one case of primary localized cutaneous nodular amyloidosis and recovered in the five water-soluble fractions (fractions I-V). Immunoblot assay of amyloid fibril proteins demonstrated that immunoreactive polypeptides with anti-kappa light chain antibody (29 kDa) and with anti-beta2-microglobulin antibody (12 kDa) were detected in fractions I-V, whereas immunoreactive polypeptide with anti-advanced glycation end product antibody (12 kDa) was detected exclusively in fractions III-V but not in fractions I and II. Two-dimensional polyacrylamide gel electrophoresis revealed that 12 kDa polypeptide in fractions I and II was electrophoretically identical with authentic beta2-microglobulin and that beta2-microglobulin in fractions III-V was advanced glycation end product-modified beta2-microglobulin with more acidic pI value. These results indicate that beta2-microglobulin is another major component of amyloid fibrils in primary localized cutaneous nodular amyloidosis and that beta2-microglobulin in primary localized cutaneous nodular amyloidosis is partly subjected to the modification of advanced glycation end product.     

Coexistence of beta2 microglobulin and lambda light chain in amyloid fibrils of dialysis-unrelated plasma cell dyscrasia-associated systemic amyloidosis

BACKGROUND: Systemic amyloidosis occurs as a result of amyloid deposition in various tissues. The amyloid fibrils in systemic amyloidosis have been reported to originate from immunoglobulin light chains. OBJECTIVE: We studied the composition of amyloid fibrils from two patients with plasma cell-associated systemic amyloidosis (PASA). METHODS: A double immunofluorescence study of the lesional skin of PASA was undertaken. Amyloid proteins were extracted with distilled water from one case of PASA. RESULTS: The double immunofluorescence study showed that anti-lambda light chain and anti-beta2 microglobulin antibodies mostly reacted with the same area of amyloid deposit. Amyloid deposits from two patients with PASA who had never undergone haemodialysis showed a positive reaction with the antibodies for beta2 microglobulin as well as immunoglobulin lambda light chain. By the use of immunoblot assay of amyloid fibril proteins, polypeptides immunoreactive with antigamma light chain antibody (29 kDa) and with anti-beta2 microglobulin antibody (12 kDa) were detected. CONCLUSIONS: These results indicate that beta2 microglobulin is a component of amyloid fibrils in PASA.     

AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma

Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.     

Primary cutaneous nodular amyloidosis associated with psoriasis

Primary cutaneous nodular amyloidosis (PCNA) presents as solitary or multiple firm, waxy nodules with a predilection for acral areas. Histologically, PCNA can be identical to myeloma‐associated systemic amyloidosis with monoclonal immunoglobulin light chain deposits. We describe a patient in whom PCNA developed in a scar in an area affected by chronic plaque psoriasis. PCNA has previously been associated with other autoimmune diseases, but to our knowledge, this is the first association with psoriasis. Interestingly, T helper (Th)17 cells, which are crucial in psoriasis pathogenesis, have recently been implicated in promotion of myeloma and plasma cell dyscrasias. The association of psoriasis and plasma‐cell light chain production in the skin, as in this case, suggests a possible role for Th17 cells in PCNA formation. The dermatopathological literature of this rare but important disease is discussed.     

系统性免疫球蛋白轻链型淀粉样变性的治疗进展

【摘要】 系统性免疫球蛋白轻链型淀粉样变性是因淀粉样蛋白原纤维聚集沉积引起的蛋白质错误折叠疾病，可导致器官不可逆性功能障碍。本文根据疾病危险分层详述本病的系统性治疗方法，低危系统性免疫球蛋白轻链型淀粉样变性患者适用化疗结合自体造血干细胞移植，中高危患者可用蛋白酶抑制剂如硼替佐米、卡非佐米及依沙唑米和免疫调节药物如来那度胺、泊马度胺及新型免疫制剂如达拉图马布、NEOD001等治疗。     

Nodular primary cutaneous amyloidosis. Isolation and characterization of amyloid fibrils

A case of nodular cutaneous amyloidosis and Sj?gren's syndrome occurred in a 63-year-old woman. Nodules had been seen for the past ten years and Sj?gren's syndrome had accompanied amyloidosis for the last three years. The concomitant occurrence of nodular cutaneous amyloidosis and Sj?gren's syndrome may not be by chance, since four of 12 cases of nodular cutaneous amyloidosis that have been reported to date in Japan were in patients with both amyloidosis and Sj?gren's syndrome. The amyloid deposits in the tissue were stained with anti-lambda light-chain amyloid antibody. Amyloid fibrils were purified from the skin lesions in this patient and were characterized biochemically, immunologically, and ultrastructurally. The results indicated that the amyloid fibrils consisted of 29,000-, 20,000-, and 17,000- dalton peptides, the 29,000-dalton peptide of which was shown to react with the lambda light chain of immunoglobulin by immunoblot study.     

Amiloidosis cutánea primaria localizada nodular con patrón diseminado

Amyloid is a proteinaceous material that is deposited in the tissues in a large variety of clinical contexts; in the skin it can be found with or without concomitant systemic disease. Primary localized cutaneous amyloidosis encompasses those amyloidoses restricted to the skin without involvement of other systems. The most common forms within this group are macular and lichen amyloidosis. Nodular amyloidosis is extremely rare, and there are notable differences in clinical presentation, prognosis, histology, and pathogenesis between this entity and the macular and lichenoid variants.We report a new case of nodular primary localized cutaneous amyloidosis with disseminated plaques and nodules in which no systemic disease developed in the 3 years following the appearance of the lesions.     

Primary Localized Cutaneous Nodular Amyloidosis Following Local Trauma

Primary localized cutaneous nodular amyloidosis (nodular amyloidosis) is a rare and distinct type of amyloidosis, in which amyloid L deposition is limited to the skin and typically manifested as a tumefactive nodule on the acral sites. However, the definite cause of nodular amyloidosis is still unknown. Although it is relatively well known that the amyloid deposits in nodular amyloidosis originate from immunoglobulin light chains secreted by local plasma cells, traumatic injury to the skin has rarely been recognized as a triggering factor of nodular amyloidosis. Herein, we present a case of a 50-year-old male patient with primary localized cutaneous nodular amyloidosis, which occurred after local trauma, and discuss the relationship between traumatic damage and dermal amyloid L deposition.     

Extended survival of patients with primary systemic amyloidosis.

Systemic amyloidosis can produce a wide variety of clinical manifestations, including characteristic cutaneous findings. Large series of patients with primary systemic amyloidosis have shown that systemic amyloidosis, with or without associated myeloma, has a median survival of no more than twenty-four months. We present a case of systemic amyloidosis that has been present in a woman for eighteen years, as manifested by periorbital purpura and an immunoglobulin G kappa light chain paraproteinemia. She was otherwise healthy; results of bone marrow examination showed no overt myeloma. We speculate that kappa light chain paraproteinemia could prove to be a marker for a more benign type of systemic amyloidosis.     

Nodular amyloidosis: review and long-term follow-up of 16 cases

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.     

Nodular primary localized cutaneous amyloidosis: immunohistochemical evaluation and treatment with the carbon dioxide laser

Nodular primary localized cutaneous amyloidosis is an uncommon disorder for which there is no consistently satisfactory treatment. The amyloid fibrils are thought to have an immunoglobulin light chain derivation and systemic involvement must be excluded in all cases. We report a patient with a large scalp lesion of nodular primary localized cutaneous amyloidosis whose immunohistochemical evaluation revealed lambda light chain deposits and who thus far has no apparent systemic involvement. The lesion was treated by the carbon dioxide (CO2) laser with excellent cosmetic results and minimal morbidity.     

Primary systemic amyloidosis presenting as extensive cutaneous ulceration

BACKGROUND: We report a case of primary systemic amyloidosis in a 78-year-old Caucasian woman presented as a nonhealing ulcer on the right thigh for 3 months. Histopathology of the skin revealed widely thickened walls of middermal and subcutaneous vessels from deposition of amorphous eosinophilic material that stained positively with Congo red and crystal violet. OBJECTIVE: This case represents a very unusual presentation of primary systemic amyloidosis, one in which the cutaneous manifestations provided the first signs of a devastatingly widespread multiorgan infiltration of amyloid protein. CONCLUSION: This presentation of the disease may signify an advanced stage with a grave prognosis as our patient passed away 3 months after development of the cutaneous ulceration.     

Systemic amyloidosis presenting with glans penis involvement

Penile amyloidosis has been reported on many occasions in the literature, but all of these have been forms of primary cutaneous amyloidosis. Systemic amyloidosis presenting with a penile ulcer as the first manifestation has not previously been reported. We present two patients in whom an ulcer of the glans penis was the first complaint that led to a diagnosis of systemic amyloidosis. In both patients, lambda light chain type amyloid was showed immunohistochemically. Both patients presented with other manifestations of systemic amyloidosis, including nail dystrophy characterized by onycholisis, trachyonychia and onychoschizia.     

Poikiloderma-like Cutaneous Amyloidosis in an Ethnic Chinese Girl

Primary cutaneous amyloidosis is the deposition of amyloid in the skin without involvement of internal organs. It is easily diagnosed when presented in its typical manifestation. Atypical or rare clinical presentations can pose diagnostic difficulties. Poikiloderma-like cutaneous amyloidosis (PCA), a rare variant of primary cutaneous amyloidosis, was first reported in the literature in 1936 (1). It is characterised by: 1) poikilodermatous skin lesions; 2) lichenoid papules; 3) cutaneous amyloid deposit in the pigmented and lichenoid lesions; 4) light sensitivity; 5) short stature; and 6) other features such as blister formation or palmoplantar keratosis. Ogino coined the term PCA syndrome when these unusual features present early in life (2). We report a 26-year-old Chinese woman who presented with poikilodermatous skin lesions and was misdiagnosed as poikiloderma atrophica vasculare (PAV) on the basis of clinical appearance without any histological proof. The diagnosis of PCA was made after skin biopsy which showed amyloid deposits in the skin. This condition can easily be confused with other true poikiloderma skin diseases. Histology is important in confirming the diagnosis.     

Relapsing bullous amyloidosis of the oral mucosa and acquired cutis laxa in a patient with multiple myeloma: a rare triple association

It is well known that primary systemic amyloidosis [light chain (AL) amyloidosis] is associated with hidden dyscrasia or multiple myeloma. Acquired cutis laxa (cutis laxa acquisita; CLA) has also been described in patients with plasma cell dyscrasias, including multiple myeloma. We report a case in which haemorrhagic oral bullae were the first sign of an undiagnosed primary systemic amyloidosis related to multiple myeloma IgG‐λ and previously diagnosed CLA. There is only one report in literature of this rare triple association; however, in that case the patient did not have oral mucosal involvement or bullous amyloidosis.     

A rare case of primary cutaneous plasmacytoma-like lymphoproliferative disorder following renal transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a lymphoid proliferation that develops as a complication of solid organ or bone marrow transplants. PTLD limited to the skin is very rare. Plasmacytoma-like PTLD is an uncommon variant of monomorphic PTLD. Its presentation in the skin is extraordinary with very few cases reported in the literature. We report a new case of plasmacytoma-like PTLD presenting as multiple skin nodules on the leg of a 74-year-old kidney transplant recipient. Histopathologic and immunohistochemical examination of one nodule revealed atypical plasmacytoid and plasmablastic cells that showed kappa light chain restriction and stained positive for CD138. Staging investigations excluded extracutaneous manifestations of the disease. This case is unusual for several reasons including involvement limited to the skin, plasmacytoid phenotype of the tumor, presentation 18 years following transplantation and Epstein-Barr virus negativity.     

Amyloid elastosis: analysis of the role of amyloid P component.

We report the second case of amyloid elastosis. Our patient had an underlying primary systemic amyloidosis with lambda light chain paraproteinemia. Salient clinical features included a sclerodermatous facial appearance, cordlike thickening of superficial blood vessels, neck skin resembling that in pseudoxanthoma elasticum, livedo reticularis-like changes on the trunk, Raynaud's phenomenon, arterial and venous thromboses, and the nephrotic syndrome. Amyloid deposits were present in the dermis, around appendages, in blood vessel walls, and in a striking distribution surrounding individual elastic fibers, that appeared shortened and fragmented. Immunofluorescence, electron microscopic, and immunoultrastructural studies with antibodies to lambda light chain, localized the amyloid deposits to the region of the elastic fiber microfibrils, with which amyloid P component (AP) is invariably associated in normal tissues. Because AP binds amyloid fibrils, codistribution of amyloid deposits and AP in amyloid elastosis strongly supports the theory that elastic fiber-associated AP may act as a nidus for amyloid deposition.     

Histopathological and immunohistochemical study of amyloidosis cutis nodularis atrophicans—Comparison with systemic amyloidosis

Three cases of amyloidosis cutis nodularis atrophicans (ACNA) were investigated histologically and immunohistochemically to determine the nature and origin of the deposited amyloid. A pulmonary lesion from a case of nodular pulmonary amyloidosis, and cutaneous lesions from three cases of primary systemic amyloidosis, two cases of secondary systemic amyloidosis and three cases of secondary cutaneous amyloidosis following basal cell epithelioma were also examined for comparison. Histology showed infiltration of numerous plasma cells adjacent to amyloid deposits in ACNA and nodular pulmonary amyloidosis, but not in systemic amyloidosis. Immunohistochemically, the cytoplasm of the plasma cells was stained with anti-immunoglobulin light chain or anti-Bence-Jones protein antisera or both, and amyloid material stained with anti-AL antiserum in ACNA and nodular pulmonary amyloidosis. These results suggest that, in ACNA, the plasma cells may produce and secrete immunoglobulin light chains or Bence-Jones protein or both, which undergo proteolysis to protein AL or amyloid fibril proteins which have the same immunoglobulin determinants as protein AL. The product is then deposited locally to form nodules in the dermis.