Sir,

Amyloidosis encompasses various illnesses characterized by abnormal amyloid deposits in tissues outside cells. Amyloid formation stems from protein breakdown, with two variations involving amyloid derived from immunoglobulin light chains.

Amyloidosis is classified based on the patient’s clinical characteristics and the nature of amyloid deposits. Dermatologists most commonly encounter primary cutaneous forms such as macular, lichenoid, and nodular types, as well as localized secondary forms. Among these, nodular primary localized cutaneous amyloidosis (NPLCA) is exceptionally rare, with fewer than a hundred cases reported in the medical literature [1].

Nodular cutaneous amyloidosis represents a dermatological metabolic disorder characterized by the localized accumulation of amyloid proteins in the skin, devoid of systemic involvement. Typically categorized into macular, papular, and nodular subtypes, nodular amyloidosis stands out as the least common form. In nodular amyloidosis, singular or occasionally multiple nodules of varying sizes emerge, being primarily composed of dermal amyloid L deposition. Nodular amyloidosis presents distinct features, with single or occasionally multiple nodules emerging predominantly on acral regions such as the face, scalp, or extremities, although they may manifest anywhere on the skin. Typically ranging from 1 to 3 cm in diameter, these nodules exhibit a characteristic waxy, tumefactive appearance. Afflicting individuals aged between 50 and 60 years. There are no clear criteria for making the diagnosis; a biopsy is crucial. It’s a highly rare case. Below are two female patients with nodular amyloidosis on the cheeks [2–5].

A 44-year-old female patient presented with a lesion on the right cheek of five years of evolution. She exhibited a localized dermatosis on the right cheek characterized by a well-defined, yellowish plaque with telangiectasias (Fig. 1a). Dermatoscopic examination showed yellow plaques with erosions and telangiectasias (Fig. 1b) and revealed no abnormalities in the rest of the physical examination. The patient had a negative family history and a significant personal history of rheumatoid arthritis treated with Plaquenil 400 mg and prednisolone 5 mg/day, and fibromyalgia managed with pregabalin 150 mg every twelve hours. The condition began five years ago with the appearance of a small, yellowish lesion on the right cheek, gradually increasing in size. Touching or covering the lesion caused bleeding, and occasionally, it turned red. A biopsy was performed, diagnosing the lesion as cutaneous morphea, yet no treatment was administered. Given these findings, a diagnosis of yellowish plaque under study was made, prompting a new biopsy of the patient’s lesion. Histopathology of the new biopsy showed an atrophic epidermis with the shape of red net stratum corneum, papillary dermis to hypodermis. There was a cohesive dissociation with amyloid deposit that became more evident with a positive red Congo stain (Fig. 2a and b) and revealed a final diagnosis of cutaneous amyloidosis. Unfortunately, there has been no further follow-up from the patient.

	Figure 1: (a) Close-up of the patient’s yellowish plaque with two erosions. (b) Dermoscopy showing the yellowish plaque, telangiectasias, and the presence of erosions.
	Figure 2: (a and b) Atrophic epidermis with the shape of red net stratum corneum, papillary dermis to hypodermis. Cohesive dissociation with an amyloid deposit that became more evident with a positive red Congo stain.

A 42-year-old female patient consulted in 2019 due to a burn from boiling water on her left arm present for five days. Upon examination of the rest of her skin and its appendages, a plaque of the same color as the skin was observed in the right preauricular region with an undetermined etiology. She reported having this lesion since she was 16 years old and that it did not cause any discomfort. A biopsy was recommended, yet the patient did not return for further consultation. Her family and personal medical history was negative.

In June 2024, she returned seeking further evaluation and diagnosis. On examination, she presented with a localized dermatosis in the right preauricular region characterized by a reddish, infiltrated plaque with poorly defined borders (Fig. 3a). Dermoscopy revealed yellowish-white lesions with some telangiectasias and a cotton wool-like appearance (Fig. 3b). Based on these findings, a skin biopsy was performed with presumptive diagnoses of sebaceous nevus, cutaneous amyloidosis, or xanthomas.

Figure 3: (a) Reddish, infiltrated plaque with poorly defined borders in the right preauricular region. (b) Dermoscopy showing yellowish-white lesions with some telangiectasias and a cotton wool-like appearance.

A skin biopsy stained eosinophilic deposits on the papillary dermis (Fig. 4a) and around a sebaceous gland (Fig. 4b), stained with Congo red. Apple green fiber around a sebaceous gland was seen under polarizing light (Fig. 4c) A histopathological study confirmed the diagnosis of cutaneous amyloidosis.

Figure 4: (a and b) HE stains eosinophilic deposits in the papillary dermis and around the sebaceous gland. (c) Apple green fiber around a sebaceous gland seen under polarizing light.

These cases of cutaneous amyloidosis are reported for their interesting localization and rare manifestation of this disease.

Amyloidosis encompasses a diverse range of illnesses marked by abnormal deposits of amyloid outside cells within tissues. The formation of amyloid is attributed to the breakdown of various proteins and has multiple sources. Two variations involve amyloid derived from the light chains of immunoglobulins: primary systemic amyloidosis and nodular amyloidosis. Both are indicative of plasma cell disorders. In nodular amyloidosis, this abnormality is localized, carrying a minimal risk of progressing to systemic illness [2].

Cutaneous amyloidosis is categorized into macular, papular, and nodular subtypes. Among these, nodular amyloidosis stands out as the least common form of primary localized cutaneous amyloidosis, possessing unique characteristics that differentiate it from the other two subtypes. Solitary or occasionally multiple nodules tend to develop primarily on the acral regions, frequently appearing on the face, scalp, or extremities, although they may occur anywhere on the skin. These nodules typically appear in individuals aged between 50 and 60 years (with a mean age of 55 years), with no apparent sex preference [2].

Clinically, macules are common manifestations characterized by dark brown or gray spots measuring two to three millimeters in diameter. They are typically itchy and are commonly found on the chest, extremities, and face. These lesions contain deposits of amyloid and light chains of immunoglobulins, suggesting local production of amyloid by infiltrated plasma cells rather than in the bone marrow. Skin lesions present as one or multiple subcutaneous erythematous brownish nodules, with a waxy appearance and firm consistency [3].

They often exhibit telangiectasias and hemorrhage (purplish discoloration) on the surface. At times, atrophy may be observed in the center; however, the lesions are usually asymptomatic. Generally, the prognosis is benign over the years, yet sometimes there may be progression from localized nodular lesions to systemic amyloidosis in less than 15% of cases [3].

There are no clinical criteria for diagnosis. The diagnostic procedure involves fine needle biopsy, which includes subcutaneous fat and the affected area’s surface [3].

From a histopathological perspective, there may be atrophic alterations in the uppermost layer of the skin, known as the epidermis. The dermis, and occasionally the subcutaneous layer beneath it, appears replete with amorphous, eosinophilic, and a uniform amyloid substance. Additionally, amyloid deposits may be detected within the small blood vessel walls and surrounding adipocytes. A scattered concentration of plasma cells may also be found interspersed within these amyloid deposits. The dermal amyloid L protein originates from immunoglobulin light chains generated by plasma cells infiltrating the local area. The exact reason for this localized plasma cell infiltration remains unclear. Unlike macular or papular amyloidosis, traumatic epidermal injury is not believed to contribute to nodular amyloidosis [2,4].

The amyloid deposit occupies the entire dermis down to the subcutaneous tissue, composed of light chains of immunoglobulins (kappa and/or lambda). It is often associated with a plasma cell infiltrate localized around the vessels or skin adnexa. It is estimated that 7% of cases progress to systemic disease, hence long-term follow-up is recommended [4].

There are no clinical criteria for diagnosis. Amyloidosis is a condition that is clinically suspected. The diagnostic procedure involves fine needle biopsy that includes subcutaneous fat and the affected surface.

The treatment recommendations vary widely as there is no treatment that demonstrates greater efficacy over others. Only symptomatic patients should be treated. Topical treatments include corticosteroids (betamethasone), calcipotriol, 0.1% tacrolimus, and topical dimethyl sulfoxide. Nodules may be removed via surgery or treated with corticosteroid injections, cryotherapy, laser, among others. However, recurrence is frequent [3,4].

Nodular amyloidosis, although rare, should be included in the differential diagnosis of infiltrated, nodular, or tumoral plaques, especially when located in acral areas. We emphasize the importance of excluding systemic disease and conducting follow-up [5].

Consent

The examination of the patient was conducted according to the principles of the Declaration of Helsinki.

The authors certify that they have obtained all appropriate patient consent forms, in which the patients gave their consent for images and other clinical information to be included in the journal. The patients understand that their names and initials will not be published and due effort will be made to conceal their identity, but that anonymity cannot be guaranteed.

REFERENCES

1.Feito M, Garcia J, Pagán B, Mariño A, Vidaurrázaga D, Arcaya C, et al. Disseminated nodular primary localized cutaneous amyloidosis. Actas Dermosifiliogr. 2008;99:648-52.

2.Lee D, Kim Y, Lee J, Kim M, Yoon T. Primary localized cutaneous nodular amyloidosis following local trauma. Ann Dermatol. 2011;23:515-8.

3.García M, Alegre M, Val-Bernal J. Amiloidosis nodular:A propósito de un caso. Rev Esp Patol. 2008;41:41-4.

4.Moon A, Calamia K, Walsh J. Review and long-term follow-up of 16 cases. Disponible en:https://goo.su/mH9W.

5.Rendón A, MascaróJ. Amiloidosis nodular cutánea primaria. Actas Dermosifiliogr. 2024;115:164-5.