|Year : 2019 | Volume
| Issue : 1 | Page : 38-41
Primary localized cutaneous amyloidosis – A clinicopathological study
Suguna Belur Venugopal, Aparna Muralidhar
Department of Pathology, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka, India
|Date of Web Publication||12-Jun-2019|
Dr. Aparna Muralidhar
Department of Pathology, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Cutaneous amyloidosis can be a manifestation of a systemic disorder or can result from localized process confined to the skin. Involvement of apparently normal skin is known as primary localized cutaneous amyloidosis. Histopathologically, amyloid appears as amorphous, eosinophilic material with hematoxylin and eosin stain. Congo red staining with apple-green birefringence under polarized microscopy confirms the diagnosis. Materials and Methods: Thirty-nine patients with a differential diagnosis of cutaneous amyloidosis reporting to the dermatology outpatient department of our hospital from November 2015 to May 2018 were studied. Twenty-six cases showed features of amyloidosis on histopathology. These were categorized into morphologic types of amyloidosis and correlated with the available clinical history. Congo red staining and observation under polarized microscope were done. Results: We encountered lichen and macular types of cutaneous amyloidosis with slight female predominance. Majority of the lesions were pruritic with involvement of the pretibial region. A history of friction was given by a few. All cases diagnosed clinically were concordant histopathologically. However, a single case of lichen amyloidosis was diagnosed solely based on histology. Microscopically, hyperkeratosis, amyloid deposits in the papillary dermis, and perivascular inflammation were the most consistent findings. All the cases showed apple-green birefringence with Congo red stain under polarized microscope. Conclusion: Cutaneous amyloidosis can have a wide range of differential diagnosis due to its varied clinical presentation. Histopathology, with the use of special stains, helps in identifying amyloid with a high degree of accuracy.
Keywords: Amyloidosis, birefringence, Congo red
|How to cite this article:|
Venugopal SB, Muralidhar A. Primary localized cutaneous amyloidosis – A clinicopathological study. Arch Med Health Sci 2019;7:38-41
| Introduction|| |
Amyloidosis is a condition associated with a number of inherited and inflammatory disorders in which extracellular deposition of fibrillar proteins is responsible for tissue damage and functional compromise. Primary localized cutaneous amyloidosis (PLCA) is the deposition of amyloid in an apparently normal skin without deposits in the internal organs.,
Amyloid in PLCA is believed to be caused by apoptosis of keratinocytes with a filamentous degeneration. Based on the pattern of amyloid deposition and epidermal changes, primary cutaneous amyloidosis is classified as lichen amyloidosis, macular amyloidosis, nodular amyloidosis, and biphasic amyloidosis.
Lichen amyloidosis and macular amyloidosis are different manifestations of the same disease process. Lichen amyloidosis is characterized by brown-red papules that often show scaling. The papules may coalesce to form plaques with verrucous surface, clinically resembling hypertrophic lichen planus or lichen simplex chronicus. The lesions are most commonly located on the pretibial area. The lesions of macular amyloidosis present as pruritic macules in a rippled or reticulate pattern, most commonly involving the upper back. The eruptions mimic postinflammatory hyperpigmentation, frictional melanosis, resolving lichen planus, and neurodermatitis clinically.
Nodular amyloidosis is characterized by nodular deposits of light chains of immunoglobulins, with no apparent systemic involvement. The legs and face are commonly involved.
Cutaneous amyloidosis has a varied clinical presentation ranging from asymptomatic-pigmented macules to waxy translucent nodules, plaques, purpura, and sometimes, bullous lesions. Therefore, histopathologic examination is essential to arrive at a definitive diagnosis for appropriate treatment.
| Materials and Methods|| |
We undertook a 1-year retrospective and 2-year prospective study of patients with a differential diagnosis of cutaneous amyloidosis reporting to the outpatient department of dermatology in our hospital from November 2015 to May 2018. Patients having any systemic disease and autolyzed and inadequate biopsy specimens were excluded from the study. The study was approved by the ethical committee of our institute. The representative skin punch biopsies received in formalin were processed. Serial sections were taken, stained with hematoxylin and eosin (H and E) stain. The slides were evaluated and categorized into different morphologic types of cutaneous amyloidosis. Repeat histologic sections were taken from the paraffin blocks, stained with Congo red, and examined under polarized microscope for apple-green birefringence.
| Results|| |
Thirty-nine skin biopsies with a differential diagnosis of amyloidosis were received in the department of pathology of our hospital from November 2015 to May 2018. Of these, 26 cases showed features of cutaneous amyloidosis on H and E staining. Subsequent confirmation with Congo red stain followed by examination under polarizing microscope was done. We encountered only two types of cutaneous amyloidosis, i.e., lichen amyloidosis and macular amyloidosis. Lichen amyloidosis was seen in 15 cases and macular amyloidosis in 11. Among the 26 cases, 12 were males and 14 were females with a slight female predominance. The age at presentation ranged from 20 to 70 years, with a mean of 42.68 years. Ten patients had the lesions for >5 years, 7 for 1–5 years, and 9 of them for 3 months–1 year, thereby signifying the chronicity of PLCA.
Clinically, patients with lichen amyloidosis presented with pruritic papules [Figure 1] of long duration (>1 year), involving predominantly the pretibial region. About 26.7% gave a history of friction. Those with macular amyloidosis had pruritic macules, patches, and maculopapular lesions [Figure 2] of variable duration. Only one patient with macular amyloidosis gave a history of friction. Pretibial involvement was seen in 16 cases (11 cases of lichen amyloidosis and 5 cases of macular amyloidosis). Extensor aspect of the upper limbs was the next most frequently affected site and was seen in five cases each of lichen amyloidosis and macular amyloidosis. The back was involved in four cases (one case of lichen amyloidosis and three cases of macular amyloidosis). Features suggestive of systemic involvement were not seen in any of the cases.
Histopathological examination of all the cases of lichen amyloidosis showed deposits of eosinophilic amorphous acellular material. Cong red staining showed these deposits as reddish-orange substance which exhibited apple-green birefringence under polarized microscopy.
The following changes were observed in lichen amyloidosis:
- Epidermis – Hyperkeratosis in all cases, parakeratosis in 2 cases (13.3%), acanthosis in 8 (53.3%), basal cell vacuolar degeneration in 7 (46.67%), and melanin in the stratum corneum in 6 (40%)
- Dermis – Amyloid in the papillary dermis and perivascular inflammatory infiltrate in all cases and melanin incontinence in 6 cases (40%).
Of the 11 cases of macular amyloidosis, variable amount of dermal amyloid was identified in all cases with H and E stain followed by Congo red stain and polarized microscopy. All cases showed hyperkeratosis. Other epidermal changes were parakeratosis in 1 (9%), acanthosis in 3 (27.28%), and basal cell vacuolization in 7 (63.64%). Dermis showed melanin incontinence in 9 (81.9%) and perivascular inflammatory infiltrate in 10 (90.9%) cases. The above findings are summarized in [Table 1].
[Figure 3], [Figure 4], [Figure 5] show the microscopic findings.
|Figure 4: Photomicrograph showing reddish-orange deposits (arrows) in the papillary dermis (Congo red stain, ×100)|
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|Figure 5: Photomicrograph showing apple-green birefringence (arrows) under polarized microscope (Congo red stain, ×100)|
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| Discussion|| |
The etiopathogenesis of primary cutaneous amyloidosis is still elusive. Female gender, racial factors, exposure to sunlight, friction, and atopy have been considered as the predisposing factors. Kumakiri and Hashimoto proposed that epidermal keratinocytes undergo filamentous degeneration in six stages, resulting in the formation of amyloid. These included fibrillar changes in the cytoplasm of epidermal keratinocytes in Stage 1 and degeneration of cell organelles and bundle formation by tonofilaments in Stage 2. Stage 3 and 4 comprised filamentous cells and masses, respectively, culminating in the formation of amyloid in Stages 5 and 6. Histochemically, early stages of amyloidogenesis did not stain with periodic acid - schiff (PAS), thioflavin T, and Congo red. A dermal component was thought to be necessary for full development of amyloid islands with an interaction between macrophages and filamentous masses playing a role. Macsween and Saihan and Hashimoto et al. found patients of Asian origin to have a higher rate of the lichen and the macular subtypes than patients of Caucasian origin. Frequent use of nylon cloth for exfoliating skin was suggested to be the likely reason.
Several cases of rare variants of primary cutaneous amyloidosis, such as papular amyloidosis of the auricular concha ( first reported in1988), have been reported. Amyloidosis cutis dyschromica is another rare variant, described by Morishima, characterized by reticular hyperpigmentation with hypopigmented macules almost all over the body, little or no itching, onset before puberty, and focal subepidermal amyloid deposition. Only 49 cases have been described till date. Bullous amyloidosis may have systemic involvement and a genetic component.
In the present study, lichen amyloidosis was more common (57.7%) than macular amyloidosis (42.3%). A similar distribution was found by al-Ratrout and Satti and Jayabhanu et al. Some studies have shown a predominance of macular amyloidosis., The mean age at presentation was 42.68 years similar to the study by Salim et al. Overall, slight female preponderance was noted in our study. The duration of the symptoms ranged from 3 months to >5 years. This finding concurred with previous studies indicating the chronicity of this disorder.
About 20 out of 26 patients had pruritus as the time of presentation. Weyers et al. are of the opinion that chronic scratching seems to be the cause and not the result of deposits of amyloid. Hence, treatment should be directed toward the amelioration of pruritus.
Histopathologically, hyperkeratosis and amyloid deposition in the papillary dermis with perivascular inflammation were consistently seen in all cases, similar to the findings of Salim et al. and Vijaya et al.
An uncommon finding in our study was the presence of melanin granules in the stratum corneum in six cases. Brownstein and Helwig have also reported a few such cases. One patient presented with xerotic patches over the anterior aspect of the thigh. Clinical differentials were leprosy, xerotic eczema, and mycosis fungoides. Histopathology showed features of lichen amyloidosis and was confirmed by Congo red staining.
The sensitivity of Congo red staining in the detection of amyloid in our study was 100%. Various techniques are available to demonstrate amyloid. Direct assessment of the fibril type by immunohistochemistry, proteomics, and occasionally, fibril sequencing are available today to identify the type of amyloid. However, the gold standard is Congo red staining. Electron microscopy may aid in diagnosis.
| Conclusion|| |
Cutaneous amyloidosis has varied clinical presentation. Histopathology, along with the use of special stains, helps in identifying amyloid deposits with a high degree of accuracy, thereby confirming the clinical diagnosis.
Congo red staining followed by observation under polarized microscope is the gold standard for confirming the diagnosis. However, our study showed no difference in identifying amyloid by routine H and E stain and by Congo red stain. This emphasizes the need for meticulous examination of the biopsy in identifying cutaneous amyloid deposits. Histomorphology, in correlation with the clinical features and history, enables an accurate etiopathologic diagnosis, thereby enhancing patient care.
We thank the Department of Oral Pathology, Vokkaligara Sangha Dental College and Hospital, for permitting us to use the polarizing microscope and Dr. Shashikiran, Senior resident, Department of Dermatology, for providing the clinical photographs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kumar V, Abbas AK, Aster JC. Diseases of the immune system. Robbins & Cotran Pathologic Basis of Diseases. 9th
ed. New Delhi: Elsevier; 2015. p. 256-62.
Maize J, Maize J, Metcalf J. Metabolic diseases of the skin. In: Elder DE, Elenitsas R, Johnson BL, Murphy BF, editors. Lever's Histopathology of the Skin. 9th
ed. Philadelphia: Lippincott Williams and Wilkins; 2005. p. 435-65.
Sarkany RP, Breathnache SM, Morris AA. Metabolic and nutritional disorders. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th
ed., Vol. 3. West Sussex: Wiley Blackwell; 2009. p. 59.42-58.
Kumakiri M, Hashimoto K. Histogenesis of primary localized cutaneous amyloidosis: Sequential change of epidermal keratinocytes to amyloid via filamentous degeneration. J Invest Dermatol 1979;73:150-62.
Kobayashi H, Hashimoto K. Amyloidogenesis in organ-limited cutaneous amyloidosis: An antigenic identity between epidermal keratin and skin amyloid. J Invest Dermatol 1983;80:66-72.
Padhiar B, Karia U, Shah B. Primary cutaneous amyloidosis. Indian J Dermatol Venereol Leprol 1997;63:105-6.
] [Full text]
Wong CK. History and modern concepts. Clin Dermatol 1990;8:1-6.
Jayabhanu AA, Bubna AK, Rangarajan S, Veeraraghavan M, Joseph LD, Sundaram M. A clinicopathologic study of cutaneous amyloidosis at a tertiary health care center in South India. Pigment Int 2016;3:17-23. [Full text]
Macsween RM, Saihan EM. Nylon cloth macular amyloidosis. Clin Exp Dermatol 1997;22:28-9.
Hashimoto K, Ito K, Taniguchi Y, Yang F, Youngberg G. Keratin in cutaneous amyloidoses. Clin Dermatol 1990;8:55-65.
Neff AG, McCuin JB, Mutasim DF. Papular amyloidosis limited to the ears. J Am Acad Dermatol 2010;62:1078-9.
Kuseyri O, Haas D, Lang N, Schäkel K, Bettendorf M. Amyloidosis cutis dyschromica, a rare cause of hyperpigmentation: A new case and literature review. Pediatrics 2017;139. pii: e20160170.
al-Ratrout JT, Satti MB. Primary localized cutaneous amyloidosis: A clinicopathologic study from Saudi Arabia. Int J Dermatol 1997;36:428-34.
Mehrotra K, Dewan R, Kumar JV, Dewan A. Primary cutaneous amyloidosis: A Clinical, histopathological and immunofluorescence study. J Clin Diagn Res 2017;11:WC01-5.
Krishna A, Nath B, Dhir GG, Kumari R, Budhiraja V, Singh K. Study on epidemiology of cutaneous amyloidosis in Northern India and effectiveness of dimethylsulphoxide in cutaneous amyloidosis. Indian Dermatol Online J 2012;3:182-6.
] [Full text]
Salim T, Shenoi SD, Balachandran C, Mehta VR. Lichen amyloidosus: A study of clinical, histopathologic and immunofluorescence findings in 30 cases. Indian J Dermatol Venereol Leprol 2005;71:166-9.
] [Full text]
Wang WJ, Chang YT, Huang CY, Lee DD. Clinical and histopathological characteristics of primary cutaneous amyloidosis in 794 Chinese patients. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:101-7.
Weyers W, Weyers I, Bonczkowitz M, Diaz-Cascajo C, Schill WB. Lichen amyloidosus: A consequence of scratching. J Am Acad Dermatol 1997;37:923-8.
Vijaya B, Dalal BS, Sunila, Manjunath GV. Primary cutaneous amyloidosis: A clinico-pathological study with emphasis on polarized microscopy. Indian J Pathol Microbiol 2012;55:170-4. [Full text]
Brownstein MH, Helwig EB. The cutaneous amyloidoses. I. Localized forms. Arch Dermatol 1970;102:8-19.
Suvarna SK, Layton C, Bancroft JD. Bancroft's Theory and Practice of Histological Techniques. 7th
ed. Philadelphia: Churchill Livingstone; 2013. p. 271-87.
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