Multiple grouped vesicles on the face in a patient with multiple myeloma.

A 79-year-old man presented with pruritic purpuric papules and vesicles on the face for 2 months (Fig 1). Upon examination, the lesions were prominent on the forehead and perioral area. Further questioning revealed that the patient had been wearing a hat and mask for several months. Also, the patient was diagnosed with multiple myeloma a month prior and had recently started chemotherapy with denosumab and lenalidomide. The patient had a prior history of stroke, subclinical hypothyroidism, and osteopenia but no other drug history. A representative image of histopathology is shown (Figs 2 and 3).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: What is the most likely diagnosis?A.Colloid miliumB.AngiosarcomaC.Systemic amyloidosisD.Lipid proteinosisE.Pseudoxanthoma elasticum Answers:A.Colloid milium – Incorrect. Colloid milium is a rare degenerative cutaneous deposition disorder characterized by the yellowish translucent papules on the sun-exposed area. Amorphous eosinophilic material is deposited in the papillary dermis, separated by a prominent thin rim of collagen or elastic tissue.B.Angiosarcoma – Incorrect. Angiosarcoma is a rare malignant vascular tumor of endothelial cell origin. The head and neck are the most commonly affected sites and is often presented as bruise-like purpura or purpuric papules/nodules.C.Systemic amyloidosis – Correct. Amyloidosis is a pathologic entity characterized by the presence of homogenous hyaline materials. It shows various clinical presentations. Pinch and periorbital purpura, ecchymosis, and macroglossia may often suggest cutaneous involvement. Nodules, scleroderma, bullous lesions, alopecia, and nail dystrophy may also present as early symptoms.1Andrei M. Wang J.C. Cutaneous light chain amyloidosis with multiple myeloma: a concise review.Hematol Oncol Stem Cell Ther. 2019; 12: 71-81https://doi.org/10.1016/j.hemonc.2018.09.003Crossref PubMed Scopus (21) Google Scholar,2Wechalekar A.D. Gillmore J.D. Hawkins P.N. Systemic amyloidosis.Lancet. 2016; 387: 2641-2654https://doi.org/10.1016/S0140-6736(15)01274-XAbstract Full Text Full Text PDF PubMed Scopus (567) Google Scholar Immunohistochemistry with Congo red could confirm the presence of amyloid deposits on the subcutaneous layer and perivascular lesions.D.Lipid proteinosis – Incorrect. Lipid proteinosis is a rare genetic disorder caused by a mutation of extracellular matrix protein. It presents in early childhood with hoarseness of voice, skin infiltration, and thickening. Recurrent blistering leading to hemorrhagic crusting and scarring are common on the face and extremities. Skin biopsy shows deposition of periodic acid–Schiff stain-positive amorphous hyaline material in the papillary dermis.E.Pseudoxanthoma elasticum – Incorrect. Pseudoxanthoma elasticum is a heritable disorder showing progressive calcium hydroxyapatite deposition on the elastic tissue. It often presented as multiple yellowish flat papules on the neck and flexural areas. Fragmented, thickened, mineralized elastic fibers are shown in the dermis. Question 2: Which diagnostic testing would be most helpful for diagnosing systemic amyloidosis in this patient?A.Genetic testing for mutations in FGA (fibrinogen alpha-chain) geneB.Tzanck smearC.Polarizing microscopyD.Abdominal fat pad biopsyE.Renal biopsy Answers:A.Genetic testing for mutations in FGA (fibrinogen alpha-chain) gene – Incorrect. Mutations in the FGA gene cause FGA amyloidosis, which is inherited in an autosomal dominant fashion. It is characterized by nephrotic proteinuria that rapidly progresses to renal failure.3Stangou A.J. Banner N.R. Hendry B.M. et al.Hereditary fibrinogen A α-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation.Blood. 2010; 115: 2998-3007https://doi.org/10.1182/blood-2009-06-223792Crossref PubMed Scopus (102) Google Scholar,4Obici L. Perfetti V. Palladini G. et al.Clinical aspects of systemic amyloid diseases.Biochim Biophys Acta. 2005; 1753: 11-22https://doi.org/10.1016/j.bbapap.2005.08.014Crossref PubMed Scopus (220) Google Scholar As our patient had multiple myeloma and did not show evidence of renal involvement, screening for FGA gene mutations is unnecessary.B.Tzanck smear – Incorrect. Tzanck smear is a simple and rapid cytologic test often used for diagnosing herpetic infection. The presence of multinucleated giant cells (Tzanck cells) strongly suggests infection with herpes simplex or varicella-zoster virus.C.Polarizing microscopy – Correct. Histological confirmation with apple-green birefringence on Congo-red stained amyloid under polarized light microscopy is essential for the diagnosis of amyloidosis. Further immunohistochemistry, including monoclonal antibodies against transthyretin, serum amyloid A, lysozyme, and Kappa and Lambda light chain, would help identifying specific subtypes of amyloidosis.D.Abdominal fat pad biopsy – Incorrect. Abdominal fat pad biopsy is a reliable screening method for amyloidosis with minimal risk.2Wechalekar A.D. Gillmore J.D. Hawkins P.N. Systemic amyloidosis.Lancet. 2016; 387: 2641-2654https://doi.org/10.1016/S0140-6736(15)01274-XAbstract Full Text Full Text PDF PubMed Scopus (567) Google Scholar However, as amyloid deposition in the skin was confirmed with the skin biopsy, an additional abdominal fat pad biopsy is not needed.E.Renal biopsy – Incorrect. A tissue biopsy of the affected organs is necessary for the diagnosis of amyloidosis. However, invasive procedures, including renal biopsy, are not recommended unless organ involvement is clinically suspected. Baseline organ function tests, including kidney and heart, should be performed first.2Wechalekar A.D. Gillmore J.D. Hawkins P.N. Systemic amyloidosis.Lancet. 2016; 387: 2641-2654https://doi.org/10.1016/S0140-6736(15)01274-XAbstract Full Text Full Text PDF PubMed Scopus (567) Google Scholar Question 3: Which of the following amyloid fibril proteins is most likely to cause amyloidosis in this patient?A.TransthyretinB.Immunoglobulin light chainC.Serum amyloid AD.Galectin 7E.Cystatin C Answers:A.Transthyretin – Incorrect. Transthyretin amyloidosis is one of the major systemic amyloidosis, characterized by the deposition of misfolded transthyretin. It could be presented as both hereditary or acquired transthyretin amyloidosis.2Wechalekar A.D. Gillmore J.D. Hawkins P.N. Systemic amyloidosis.Lancet. 2016; 387: 2641-2654https://doi.org/10.1016/S0140-6736(15)01274-XAbstract Full Text Full Text PDF PubMed Scopus (567) Google Scholar Transthyretin amyloidosis may be associated with eyelid and peripheral ecchymosis, atrophic scar, bullous lesions, thickened skin, and xerosis.B.Immunoglobulin light chain – Correct. Amyloid light chain amyloidosis is caused by excessive accumulation of an immunoglobulin light chain protein produced by aberrant plasma cells.5Vela-Ojeda J. García-Ruiz Esparza M. Padilla-González Y. et al.Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor.Ann Hematol. 2009; 88: 59-66https://doi.org/10.1007/s00277-008-0554-0Crossref PubMed Scopus (42) Google Scholar Amyloid light chain amyloidosis is associated with multiple myeloma in 10% to 20% of patients. Also, the deposited materials stained positively with Kappa and Lambda chains, as in our patient.C.Serum amyloid A – Incorrect. Reactive systemic amyloidosis is secondary amyloidosis caused by prolonged inflammation. It could be developed in any long-term inflammatory diseases and is often associated with chronic infections, rheumatic, or auto-inflammatory diseases.D.Galectin 7 – Incorrect. Galectin 7 is accumulated in the localized types of amyloidosis.E.Cystatin C – Incorrect. Hereditary cystatin C amyloid angiopathy is a rare form of amyloidosis caused by a mutation in cystatin C. Mutated cystatin C predominantly invades brain arteries and arterioles, leading to recurrent cerebral hemorrhages. None disclosed.