Localized Cutaneous Amyloidosis Research Articles

Evaluation and comparison of Q-switched Nd: YAG laser 1064 nm and Er: YAG laser 2940 nm in the treatment of macular amyloidosis.

Macular amyloidosis (MA) is one of the most common types of primary localized cutaneous amyloidosis (PLCA), distributed predominantly over the trunk and extremities. Due to the vast therapeutic options, this study aims to compare the effectiveness of Q-switched Nd: YAG laser 1064 nm and Er: YAG laser 2940 nm in treating MA. This clinical trial was performed in 2020-2021 on 33 women with MA. In each patient, the lesion was randomly divided into two areas, A and B. Area A underwent four treatment sessions with 4-week intervals of Q-switched Nd: YAG laser 1064 nm. Area B underwent four treatment sessions with an Er: YAG laser 2940 nm at 4-week intervals. Degree of basal pigmentation and degree of pigmentation after treatment, pruritus intensity, before and after the treatment, and patient and physicians' satisfaction were measured and compared. The pruritus in patients improved significantly after the study (P < 0.001), but no significant differences could be observed between the two groups regarding the improvements (P > 0.05). We also found no significant differences between the two groups of patients regarding patient and physicians' satisfaction rates (P > 0.05). The use of both Q-switched Nd: YAG laser and Er: YAG laser resulted in improvements in terms of pruritus, patient and physicians' satisfaction, and total improvement in pigmentation of the lesions.

A prospective interventional study on efficacy of fractional carbon dioxide laser in primary cutaneous macular amyloidosis

Background: Macular amyloidosis (MA) represents a common variant of primary localized cutaneous amyloidosis (PLCA). Many therapeutic modalities, including topical and systemic medications, phototherapy, photochemotherapy, dermabrasion, and lasers have been suggested for PLCA with variable efficacy. Over the past decade, several studies have reported successful treatment of PLCA with different types of lasers. Aim: To evaluate the efficacy and safety profile of fractional carbon dioxide laser (FrCO2) in primary cutaneous MA. Methods: Using the consecutive sampling technique, 30 clinically confirmed cases of MA aged 18 years and above attending the dermatology out-patient department were recruited for a prospective, single group, interventional study. Each patient received three sessions with 4 weeks interval and then subsequently monitored for 20 weeks. The degree of pigmentation, rippling, itching, overall progress, and patient satisfaction were graded and compared for each patient. SPSS software version 23.0 was used for data analysis. Results: There was a statistically significant (P &lt; 0.001) improvement in the mean percentage of the degree of pigmentation, itching (P &lt; 0.001), and rippling scores (P = 0.03). Marked patient satisfaction was noted at 20 weeks. The excellent safety profile was noted. Conclusion: Our study has shown a positive response to treating MA with FrCO2 laser. Patients were highly satisfied, as there was a significant reduction in itching, pigmentation, and area of the skin lesion with no significant side effects. Our study points towards better efficacy of FrCO2 laser in MA with a good safety profile and better patient satisfaction.

Primary Localized Cutaneous Amyloidosis in Central Europe: A Retrospective Monocentric Study on Epidemiology and Therapy.

Amyloid deposits can be the cause of many chronic diseases. Primary localized cutaneous amyloidosis (PLCA) is a chronic dermatologic condition with amyloid deposits in the papillary dermis. The most common types of the keratinocyte-derived form of PLCA include macular (MA), lichen (LA), and biphasic (BA) amyloidosis. The estimated prevalence of PLCA in the Asian population is 0.98/10,000, which is higher than in the European population; thus, epidemiologic data on PLCA in the Caucasian population are limited. We performed a retrospective single-center study analyzing epidemiologic characteristics of a Central European PLCA population. Epidemiologic data regarding age, sex, skin phototype (Fitzpatrick scale I-VI), disease duration, comorbidities, history of atopy, and family history of PLCA were collected. Clinical characteristics, localization of PLCA lesions, applied therapies and treatment outcomes were also analyzed. Dermoscopic characteristics were also evaluated. A total of 41 patients diagnosed with PLCA were included, with 22 presenting with macular, 18 with lichen, and 1 with biphasic amyloidosis. The male/female ratio was 16/25, and mean age at diagnosis was 54.6 ± 15.2 years (range 27-87 years). The mean age at the onset of PLCA was 53 ± 16.1 years (range 19-79 years) in MA, 46.7 ± 18.2 years (range 14-73 years) in LA, and 26 years in BA. The interscapular region in MA and the extensor surface of the lower extremities in LA proved to be localization-related areas. In our center, a wide range of therapeutic options was applied, with the most prescribed being topical corticosteroids in all types of PLCA. We presented a retrospective, monocentric study on the epidemiology of PLCA in the Central European region. By examining the medical data of a significant number of PLCA patients, we compared our epidemiologic data with that of the Asian PLCA population. Due to the rarity of the condition, further randomized controlled trials and guidelines are needed to improve therapeutic outcomes.

Dermatoscopy of primary localised cutaneous amyloidosis - A cross-sectional study in a setting of South Asian public dermatology department.

Amyloidosis, deposition of misfolded protein in body, is a fairly common condition. The deposition of misfolded proteins in skin which occurs in absence of systemic comorbidities, namely Primary Cutaneous Amyloidosis (PCA) is also a well-known entity in skin of colour patients of Asian subcontinent. Primary Cutaneous Amyloidosis is usually diagnosed with good clinical acumen and typical clinical phenotype and involved site. Dermoscope has been used as an adjunct non-invasive tool to confirm cases with diagnostic uncertainty and in those in whom biopsy is deferred. Typical dermoscopic features of PCA helps differentiate it from other pigmentary dermatoses and avoids unwanted invasive biopsies and investigations especially in resource poor settings with financial constraints. This study aims to identify and corroborate clinically, typical dermoscopic features in PCA in 42 patients which includes Macular Amyloidosis (MA) and Papular Amyloidosis (PA) predominantly in skin of colour patients from government based hospital of a south east Asian country. Patients with classic clinical features of PCA were selected. Primary Cutaneous Amyloidosis was subclassified into MA or PA and their corresponding clinically corroborative dermoscopic features were enlisted respectively. All patients (treatment naïve and previously treated), who consented to participate in the study were included. Patients were diagnosed based on the prototypical clinical features. Dermoscopy was done using DermLite III DL3N Polarised and Fluid Dermoscope w/PigmentBoost Brand (3Gen, DermLite LLC, San Juan Capistrano, CA, USA) and images were obtained to create digital dermoscopy system by attaching camera-equipped mobile device via an optional connection kit (Redmi Note 11, MIUI version 13.0.5, CHINA) and the findings were enlisted concurrently. In this study of dermoscopic findings of PCA, 42 patients were evaluated for their clinical lesions along with its corroboration with the dermoscopic features. Macular Amyloidosis was seen in 30 patients and 12 patients had typical cutaneous phenotypic and dermoscopic feature of PA. The most common dermoscopic finding seen in patients with MA was shiny to dull white, circular or oval central hub surrounded with halo of light brown dots. Most common configuration of brownish pigmentation around central hub was fine streak type. Also eccrine clues were seen in some cases of MA, which was a unique finding. Similarly in the PA subtype, the central hub was replaced by scar like structureless translucent white area surrounded by brownish black dot like structures, especially in those with large and thick plaques. Dermoscopic findings of PCA and their clinical corroboration is a much-needed aspect in treating patients with pigmentary disorders and in those with skin of colour, especially in developing countries. Utilization of dermoscope in clinical settings of low income countries and in government based hospitals will decrease the add on economic burden of invasive diagnostic modalities like biopsy and other inadvertent tests done to rule out pigmentary conditions.

DP25 Widespread subcutaneous nodular kappa light chain amyloidosis

Abstract A 69-year-old woman was referred to the dermatology department for evaluation of multiple widespread subcutaneous lesions involving the neck, torso and limbs. These lesions, initially diagnosed in the community as lipomas, had been slowly progressing in size and number for 3 years. She had remained systemically well. Her only medical history was essential thrombocythaemia. She took no regular medication. On examination, there were multiple subcutaneous lesions appreciated on palpation with no overlying epidermal change. The patient was experiencing pain in a sciatic distribution. Magnetic resonance imaging of the femur showed a 12-cm enhancing area of subcutaneous nodularity encasing the sciatic nerve. Computed tomography of the chest, abdomen and pelvis showed multiple subcutaneous, ill-defined, soft tissue lesions of the anterior abdominal wall with no lymphadenopathy or organ abnormality. Deep incisional biopsies from two separate locations were completed. There was an unremarkable epidermis and dermis. In the subcutaneous fat, the septae appeared thickened alongside thickened elastic fibres and a prominent multifocal granulomatous reaction with a high degree of elastophagocytosis. There were multifocal aggregates of plasma cells that displayed no cytological atypia. In situ hybridization showed strong kappa light chain restriction. Plasma protein electrophoresis was completed and confirmed a paraprotein band in the gamma region of IgM kappa. Full blood count revealed a high platelet count (585 × 109 cells L–1) but was otherwise unremarkable alongside normal renal and liver function, bone profile, lactate dehydrogenase, B2 microglobulin, Bence–Jones proteins and infection screen. A Congo red stain was performed on the original histological samples. This showed apple green birefringence under polarized light-confirming amyloid. Haematology completed a bone marrow biopsy, which was normal. Referral to the National Amyloid Centre was made. Serum amyloid P scan showed no visceral involvement. A diagnosis of subcutaneous amyloid kappa light chain subtype (AL) was made. The patient has since commenced rituximab, bortezomib (Velcade®), cyclophosphamide and dexamethasone (R-VCD) chemotherapy at 4-weekly intervals over a 4-month period. Primary localized cutaneous amyloidosis is characterized by extracellular deposition of amyloid protein in the skin without evidence of systemic involvement and is often subtyped into macular, papular and nodular. Amyloidoma (tumoral amyloidosis) is rare and defined as a solitary localized deposit of amyloid. There are only four case reports in the literature of multiple subcutaneous amyloid deposits, and only one of these cases was of AL (light chain) vs. amyloid A (AA) subtype. This case showed nodules restricted to the neck (Nguyen TU, Oghalai JS, McGregor DK et al. Subcutaneous nodular amyloidosis: a case report and review of the literature. Hum Pathol 2001; 32:346–8). To our knowledge, this is the first case of widespread kappa light chain subcutaneous amyloidosis.

Localized Cutaneous Nodular Amyloidosis: A Specific Cutaneous Manifestation of Sjögren's Syndrome.

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition attributed to plasma cell proliferation and the deposition of immunoglobulin light chains in the skin without association with systemic amyloidosis or hematological dyscrasias. It is not uncommon for patients diagnosed with PLCNA to also suffer from other auto-immune connective tissue diseases, with Sjögren's syndrome (SjS) showing the strongest association. This article provides a literature review and descriptive analysis to better understand the unique relationship between these two entities. To date, 34 patients with PLCNA and SjS have been reported in a total of 26 articles. The co-existence of PLCNA and SjS has been reported, especially in female patients in their seventh decade of life with nodular lesions on the trunk and/or lower extremities. Acral and facial localization, which is a typical localization of PLCNA in the absence of SjS, seems to be much more unusual in patients with associated SjS.

AHNAK, regulated by the OSM/OSMR signaling, involved in the development of primary localized cutaneous amyloidosis

BackgroundPrimary localized cutaneous amyloidosis (PLCA) is a chronic skin disease characterized by aberrant keratinocyte differentiation, epidermal hyperproliferation, and amyloid deposits. Previously, we demonstrated OSMR loss-function mutants enhanced basal keratinocyte differentiation through the OSMR/STAT5/KLF7 signaling in PLCA patients. ObjectiveTo investigate the underlying mechanisms involved in basal keratinocyte proliferation in PLCA patients that remain unclear. MethodsPatients with pathologically confirmed PLCA visiting the dermatologic outpatient clinic were involved in the study. Laser capture microdissection and mass spectrometry analysis, gene-edited mice, 3D human epidermis culture, flow cytometry, western blot, qRT-PCR and RNA sequencing were used to explore the underlying molecular mechanisms. ResultsIn this study, we found that AHNAK peptide fragments were enriched in the lesions of PLCA patients, as detected by laser capture microdissection and mass spectrometry analysis. The upregulated expression of AHNAK was further confirmed using immunohistochemical staining. qRT-PCR and flow cytometry revealed that pre-treatment with OSM can inhibit AHNAK expression in HaCaT cells, NHEKs, and 3D human skin models, but OSMR knockout or OSMR mutations abolished this down-regulation trend. Similar results were obtained in wild-type and OSMR knockout mice. More importantly, EdU incorporation and FACS assays demonstrated the knockdown of AHNAK could induce G1 phase cell cycle arrest and inhibit keratinocyte proliferation. Furthermore, RNA sequencing revealed that AHNAK knockdown regulated keratinocyte differentiation. ConclusionTaken together, these data indicated that the elevated expression of AHNAK by OSMR mutations led to hyperproliferation and overdifferentiation of keratinocytes, and the discovered mechanism might provide insights into potential therapeutic targets for PLCA.

Primary localized cutaneous amyloidosis − a review

Primary localized cutaneous amyloidosis − a review

Keratinic amyloid deposition in canine hair follicle tumors.

Keratinic primary localized cutaneous amyloidosis is a disease in humans; however, no similar condition has been reported in animals. This study aimed to investigate cutaneous keratinic amyloid deposition in dogs and elucidate its etiology. Canine hair follicle tumor tissues were histopathologically analyzed. Immunohistochemistry and mass spectrometry-based proteomic analyses were performed to identify precursor protein candidates. Structural prediction and in vitro fibrillization analyses were conducted to determine the amyloidogenic region and gene sequencing analysis was performed to assess mutations. Of the 266 samples, 16 had amyloid deposition. Amyloid deposits were found in the stroma of tumors and in the margins of keratin debris and around normal hair follicles. Cytokeratin 5 (CK5) was identified as a precursor protein candidate. C-terminal truncation of CK5 was observed in amyloid deposits, and the truncation sites varied depending on the deposition pattern. There was a significantly higher incidence of amyloid deposition in Shiba dogs, and CK5 amino acid polymorphisms were identified in these dogs. A part of the C-terminal region of both canine and human CK5 exhibited highly amyloidogenic properties in vitro. This study revealed the existence of cutaneous keratinic amyloid deposition in animals and identified CK5 as an amyloid precursor protein, providing novel insights into understanding the etiology of cutaneous amyloidosis.

Unilateral Primary Localised Cutaneous Nodular Amyloidosis of the Nipple

Background: Amyloidosis is characterised by extracellular accumulation of an amorphous fibrillary protein and can affect any organ. It is classified into systemic and localised disease according to its sites of presentation and as primary or secondary according to aetiology. Breast amyloid was first described in 1973 and is extremely rare.Case Presentation: A 61-year-old woman presented in 2020 with a 1-year history of an enlarging tender left nipple with some associated bleeding. Clinical differential diagnoses included a nipple adenoma and an intraductal carcinoma; therefore, a punch biopsy was taken. A full set of screening blood tests were undertaken which were normal, showing no evidence of a plasma cell dyscrasia.The biopsy showed diffuse replacement of the dermis by acellular eosinophilic material showing fracturing. Congo Red stain was positive showing apple-green birefringence under polarised light. A diagnosis of primary localised cutaneous nodular amyloidosis of the nipple was made.Conclusion: We present a rare documented case of isolated primary localised cutaneous nodular amyloidosis of the nipple. This can be considered as a differential diagnosis for patients with a new nipple lesion alongside nipple adenoma and intraductal carcinoma.

Pigmented squamous cell carcinoma in situ with amyloid deposition mimicking melanoma

Pigmented squamous cell carcinoma in situ with amyloid deposition mimicking melanoma

Generation of a human embryonic stem cell line (SMUDHe010-A-82) carrying a homozygous c.1538G > A (p.G513D) mutation in the OSMR gene by CRISPR/Cas9-mediated homologous recombination

Mutations in the tumor suppressor M receptor (OSMR) gene are associated with primary localized cutaneous amyloidosis (PLCA). Recently, we confirmed that OSMR loss-of-function mutations enhance epidermal keratinocyte differentiation via inactivation of the STAT5/KLF7 signaling. However, no disease model was available for PLCA. Accordingly, we generated an OSMR c.1538G > A mutant human embryonic stem cell line (SMUDHe010-A-82) using CRISPR/Cas9-mediated homologous recombination. The cell line preserves normal karyotype, pluripotency and the ability to differentiate into all three germ layers. Moreover, the cell line can be used to prepare human skin organoid, which may provide a disease model for PLCA.

Fibulin-4 Accelerates Amyloid Formation by Binding with a Keratin 5 Peptide Fragment

Keratins are the major amyloid fibril component in localized cutaneous amyloidosis. We analyzed the amyloid components in the skin of patients with localized cutaneous amyloidosis by immunohistochemical staining using antisera against extracellular matrix proteins and keratin 5 (K5). Fibulin-4 and K5 colocalized in the amyloid deposits. Using 14 synthetic peptides, we screened for amyloidogenic sequences in the C-terminal region of K5, including the α-helical rod domain and the tail domain. Two peptides stained with thioflavin T possessed a β-sheet structure and formed amyloid-like fibrils. Among the amyloidogenic peptides, a peptide KT5-6 (YQELMNTKLALDVEIATYRKLLEGE) derived from the α-helical rod domain of K5 specifically bound to fibulin-4. In addition, amyloid formation of KT5-6 was accelerated by fibulin-4. These results suggest that degraded fragments of K5 containing the KT5-6 sequence form amyloid fibrils with fibulin-4. The data further suggest that degraded fragments of K5 and fibulin-4 have the potential to initiate cutaneous amyloidosis.

The therapeutic role of lasers in primary localized cutaneous amyloidosis: a systematic review.

With the investigation of the efficacy of laser therapy in primary localized amyloidosis(PLCA) only recently starting to materialize, we aimed to review the currently available studies of laser therapy in the management of the disease. We searched PubMed, Scopus, Embase, Web of Science, Cochrane, and ProQuest online databases with a specified search strategy, assessed the quality of each study, and then extracted the eligible data. Five RCTs(randomized controlled trials), one non-randomized controlled trial, three case series, and nine case reports(18 in total) were included. Overall, carbon dioxide (CO2), neodymium-doped:yttrium aluminum garnet (Nd:YAG), pulsed dye (PDL), Er (Erbium):YAG, and yttrium/erbium fiber were the studied lasers. One hundred fifty-five cases in total underwent laser therapy, with CO2 being the most frequent laser. Almost all studies demonstrated significantly desirable outcomes, while only mild and transient side effects were noted. Even though the studies' results were significant, we noticed that implementing a consistent methodology and a standardized objective assessment method was missing. Therefore, we recommend that future studies be conducted with less heterogeneous data for a more definite conclusion.

Primary Localized Cutaneous Amyloidosis: A Retrospective Study of an Uncommon Skin Disease in the Largest Tertiary Care Center in Switzerland

Background: Primary localized cutaneous amyloidosis (PLCA) is defined by the deposition of amyloid protein in the skin without systemic involvement. There are four subtypes of PLCA: lichen amyloidosis (LA), macular amyloidosis (MA), biphasic amyloidosis (BA), and nodular amyloidosis (NA). PLCA occurs most frequently in Latin Americans and Asians. Treatment is not standardized. Objectives: To identify subtypes, demographic and clinical features and treatment efficacy in patients with histopathologically confirmed PLCA. Materials and Methods: Data of PLCA patients were extracted from the electronic hospital database and included if diagnosis of PLCA was histopathologically confirmed and if sufficient information regarding treatment and follow-up was available. The evaluation of the treatment efficacy was based on a novel score to assess the reduction of itch and skin lesions. Results: In this retrospective, monocentric study, 37 cases of PLCA diagnosed between 2000 and 2020 were included (21 females) with a mean age of 52 years. LA was the most frequent subtype found in 21 patients (56.8%), followed by MA in 10 patients (28%) and BA in 6 patients (16.2%). No cases of NA were included. 22 patients (59.4%) had skin phototype II or III. Regarding treatment, a combination of UVA1 phototherapy with high-potency topical corticosteroids seemed to show the highest efficacy with complete clearance of symptoms in 4 patients (10.8%). A substantial improvement of symptoms was found in 5 patients (12.7%) treated with high-potency topical corticosteroids alone or in combination either with UVA1 or bath PUVA or monotherapy with UVA1 phototherapy or capsaicin (0.075%) cream. Low-/medium-potency topical corticosteroids alone or in combination with UVBnb (311 nm) phototherapy showed a lower efficacy. Conclusion: Our data show that PCLA is a rare disease in central Europe but can also be expected in a predominantly Caucasian population. The best treatment response was achieved with a combination of UVA1 phototherapy and high-potency topical corticosteroids.

Primary Localized Cutaneous Amyloidosis of Keratinocyte Origin: An Update with Emphasis on Atypical Clinical Variants

Amyloid is a protein derived from at least 20 different substances. Once misfolded, it results in a group of cutaneous and systemic conditions. Primary localized cutaneous amyloidosis of keratinocyte origin is a very common subtype that can manifest either as lichen or macular amyloidosis, lacking systemic involvement. Lichen amyloidosis often presents as multiple hyperpigmented papules on the lower extremities whereas macular amyloidosis is classically characterized by dark brown rippled macules on the interscapular area. Review of the literature reveals that in addition to the classical presentation of primary localized cutaneous amyloidosis there exists a plethora of various manifestations that can be grouped into either geographic or morphologic categories. This review provides clinicians with the intimate knowledge of these presentations and summarizes the available treatment modalities.

Primary Localized Cutaneous Nodular Amyloidosis and Limited Cutaneous Systemic Sclerosis: Additional Cases with Dermatoscopic and Histopathological Correlation of Amyloid Deposition

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition due to the plasma cell proliferation and skin deposition of immunoglobulin light chains, without systemic amyloidosis or hematological dyscrasias. The association with autoimmune connective tissue diseases has been reported, especially with Sjogren’s syndrome, and in a few cases with systemic sclerosis. Herein, we describe three cases of PLCNA occurring in women with a diagnosis of limited cutaneous systemic sclerosis and review the literature on the topic to highlight a stereotypical presentation. Moreover, we support the usefulness of dermoscopy, characterized by a yellow–orange waxy pattern surrounded by telangiectasias, for a rapid and non-invasive diagnostic assessment. Thus, when asymptomatic nodules occur on lower limbs of women affected with limited systemic sclerosis, and dermoscopy identifies yellow–orange blotches, a diagnosis of PLCNA can be considered and further confirmed by histopathology. Monitoring for systemic amyloidosis development is advisable, although the risk of progression is considered very low.

Primary nodular localized cutaneous amyloidosis of the scalp associated with systemic lupus erythematosus.

Primary nodular localized cutaneous amyloidosis of the scalp associated with systemic lupus erythematosus.

FotoFinder Dermoscopy Analysis and Histopathological Correlation in Primary Localized Cutaneous Amyloidosis.

Primary localized cutaneous amyloidosis (PLCA) causes extracellular proteinaceous deposits in skin. It is clinically divided into macular amyloidosis, lichen amyloidosis and nodular amyloidosis. Atypical presentations of PLCA make the diagnosis challenging, requiring biopsy to confirm amyloid deposition in the upper papillary dermis. This study used FotoFinder dermoscopy to characterize lichen and macular amyloidosis and correlated the dermoscopic features with histopathological findings. This cross-sectional study enrolled patients with a clinical and histopathological diagnosis of PLCA. Dermoscopic examination was performed using the FotoFinder dermoscope, which provides a range of magnification from 20× to 140×. A total of 30 patients were included in the study. Common dermoscopic patterns of MA were white or brown central hubs, and common patterns of LA were white structureless, scar-like areas and central hubs. New dermoscopic findings were a day lily appearance in MA and white rosettes in LA. Dermoscopy plays a pivotal role in demonstrating characteristic findings of PLCA. These findings were well corelated with histopathology, thus avoiding unnecessary biopsy for arriving at an accurate diagnosis of PLCA.

Primary cutaneous amyloidosis: A clinicopathological, histochemical, and immunohistochemical study.

Primary cutaneous amyloidosis (PCA) comprises several forms of localized cutaneous amyloidosis characterized by amyloid deposits occurring at or near dermal-epidermal junctions. Immunohistochemical studies have shown the expression of cytokeratin (CK) suggesting that it has an epidermal origin. To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain. A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed. : The qualitative data has been expressed as proportions and the quantitative data has been expressed as mean ± SD. All data was analyzed using the Statistical Package for Social Sciences (SPSS) software version 22. Deposits of amyloid in papillary dermis were seen in all 30 cases. Mild focal basal cell vacuolar degeneration and apoptotic bodies in epidermis were seen in six cases. The presence of pigment cells in dermis were seen in 26 cases. CK5/6 showed weak/mild immunopositivity in nine cases, moderate in 20 cases, and strong in one case. The presence of dermal melanophages interspersed within eosinophilic deposits gives a clue to the diagnosis. Congo red stain highlights the deposits and visualization under polarized light gives apple green birefringence which is diagnostic of amyloid. Staining of amyloid deposits by CK5/6 proves that the amyloid is of keratinocyte origin. There was 100% sensitivity with Congo red and CK5/6. Thus, CK5/6 can be used as an adjunct tool to Congo red stain in the diagnosis of primary cutaneous amyloidosis.