bromochloroacetic-acid and Amyloidosis

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.

Topics: Adult; Aged; Amyloid; Amyloidosis; Dermis; Ear; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases

Electron-microscopic, histochemical and immunological studies have shown that the deposits of primary and secondary localized cutaneous amyloid (amyloid K) consist mainly of keratin filament material. The amyloid P component is the second most significant constituent. Pathogenetically, defective keratinocyte apoptosis is the most likely mechanism of generation for amyloid K. Apoptosis is a distinct mode of cell death according to which individual basal keratinocytes disintegrate in physiological and pathological conditions to form membrane-bound "apoptotic" bodies consisting mainly of keratin filament aggregates. These lose their protective membrane and drop into the upper dermis, where they present as keratin (Civatte, cytoid) bodies, which are regularly coated with immunoglobulins. Overproduction of keratin bodies and/or a defect in their degradation by enzymatic digestion or phagocytosis by macrophages and fibroblasts, followed by conversion into amyloid fibrils, may be responsible for the generation of deposits of amyloid K.

Topics: Amyloid; Amyloidosis; Humans; Keratins; Microscopy, Electron; Monocytes; Phagocytosis; Serum Amyloid P-Component; Skin; Skin Diseases

Topics: Amyloid; Amyloidosis; Disulfides; Histocytochemistry; Humans; Immunoglobulin G; Immunologic Techniques; Keratins; Maleimides; Microscopy, Electron; Skin Diseases; Staining and Labeling

Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal-epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34ßE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process.

Topics: Adult; Aged; Amyloid; Amyloidosis; Dermis; Ear; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases

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.

Topics: Amyloid; Amyloidosis; Animals; Dog Diseases; Dogs; Hair Follicle; Keratins; Plaque, Amyloid; Proteomics; Skin Neoplasms

There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings.. Since 2008, our reference laboratory has performed liquid chromatography/tandem mass spectrometry (LC-MS/MS) for amyloid typing. The institutional pathology archive and reference laboratory database were queried to retrospectively identify all penile surgical pathology specimens with LC-MS/MS results between January 1, 2008, and November 23, 2022. Archived H&E-stained and Congo red-stained sections were re-reviewed.. Twelve cases of penile amyloidosis were identified, which represented 0.35% (n = 3,456) of penile surgical specimens. AL-type amyloid was most frequent (n = 7), followed by keratin-type amyloid (n = 3) and ATTR (transthyretin)-type amyloid (n = 2). AL-type amyloid cases often showed diffuse dermal/lamina propria deposition, whereas all keratin-type amyloid cases were localized to the superficial dermis. Two cases with keratin-type amyloid had concomitant cutaneous findings (penile intraepithelial neoplasia and condyloma).. This series, the largest to date, demonstrates that penile amyloidosis has a heterogeneous proteomic landscape. To the best of our knowledge, this is the first study describing ATTR (transthyretin)-type penile amyloid.

Topics: Amyloid; Amyloidosis; Chromatography, Liquid; Humans; Keratins; Male; Penis; Prealbumin; Proteomics; Retrospective Studies; Tandem Mass Spectrometry

The study was undertaken to answer the question that how many patients with pigmentation of back and arms actually have amyloid deposits in pathology. 44 patients presenting with diffuse pigmentation of back and arms (DPOBA) were selected. Skin biopsies were performed in all cases from the affected sites. On all formalin fixed and paraffin embedded specimens, the following histochemical stains were performed: Haematoxylin and eosin (H&E), Congo red and immunohistochemical staining using anti-cytokeratin monoclonal antibody. In 9 of 44 cases (20%), amyloid deposits were found. In the remaining 35 cases (80%), H&E, Congo red and immunohistochemical staining failed to show any amyloid deposition. We were unable to find amyloid deposition in most of the patients presented with DPOBA. It seems that the signs may be attributable other disorders with similar clinical but different pathophysiologic aspects.

Topics: Adult; Amyloid; Amyloidosis; Antibodies, Monoclonal; Arm; Back; Biopsy; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Immunohistochemistry; Incidence; Iran; Keratins; Male; Plaque, Amyloid; Retrospective Studies; Skin; Skin Pigmentation

Amyloidosis cutis dyschromica is a rarely documented variant of cutaneous amyloidosis. To date, only 26 cases have been reported.. The purpose of this study was to improve the clinical and histopathological data for this variant of amyloidosis and to highlight the immunohistochemical features of the disease. The published cases were also reviewed.. We performed a retrospective review of patients with amyloidosis cutis dyschromica in a single centre. The clinical, histopathological and immunohistochemical features were documented and analysed.. We described 10 cases of amyloidosis cutis dyschromica. Six of them were female. Five patients were from the same family, and the other 5 were sporadic. The distinguishing features of the clinical presentation included generalised mottled hyper- and hypopigmented macules, which were asymptomatic or mild pruritic. The typical onset of the lesions occurred in childhood (n = 7) and occasionally after puberty (n = 3). No evidence of systemic amyloidosis deposition was observed in these cases of amyloidosis cutis dyschromica. Amyloid deposits were observed in the papillary dermis and were positive for the Congo red stain. An immunohistochemical study showed that the amyloid expresses cytokeratins CK34βE12 and CK5/6.. We described the largest series of amyloidosis cutis dyschromica to date and reviewed the published patients. This rare disease is featured by generalised mottled hyper- and hypopigmented lesions, and it is a rare variant of primary cutaneous amyloidosis without evidence of systemic amyloid deposition. Positive staining for the cytokeratins CK34βE12 and CK5/6 in amyloidosis cutis dyschromica suggests that the amyloid is derived from keratinocytes.

Topics: Adolescent; Adult; Aged; Amyloidosis; Congo Red; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Keratinocytes; Keratins; Male; Middle Aged; Pigmentation Disorders; Retrospective Studies; Skin Diseases; Young Adult

Cytokeratins (CKs) are expressed specifically in the cytoplasm of epithelial cells. We investigated the expression of CKs immunohistochemically in basal cell carcinomas (BCCs), epidermis overlying tumour, and skin tumor-associated amyloidosis (STA). Twenty cases of BCC, 11 of which had STA were included to the study. The primary antibodies of CK1-8 (AE3), CK10 (DEK-10), CK14 (LL002), CK17 (E3), CK18 (DC10), CK19 (KS19.1), CK 5/6/18 (LP34), CK8/18 (5D3) were applied to the section immunohistochemically. In BCCs without STA, CK1-8, CK14 and CK17 antibodies were expressed by tumour tissue in all biopsy specimens. In the BCCs with STA, tumour tissue was immunoreactive always with CK1-8 and CK17 antibodies, and commonly immunoreactive with anti-CK 14 antibody. In the epidermis overlying tumour tissue, there was positive immunoreactivity with anti-CK 1-8, CK 5/6/18, CK 10 and CK 14 antibodies in all biopsy specimens. Anti-CK 17 antibody was also positive in 17 biopsy specimens. STA is immunoreactive with anti-CK1-8 in all specimens. There was mild staining with anti-CK5/6/18 and with anti-CK19 whereas no immunoreactivity with anti-CK10 and CK18 antibodies was found. In conclusion, we could not find a significant CK expression difference between BCCs with and without STA. Weak positivity and a few number of CKs were shown in STA when compared with those of BCC and epidermis overlying tumour tissue expressing the more variable CKs. Interestingly, although CKs coexpressed in pairs consisting of one basic and one acidic CK, we detected predominantly basic CKs in STA.

Topics: Amyloidosis; Carcinoma, Basal Cell; Epidermis; Humans; Immunoenzyme Techniques; Keratins; Skin Neoplasms; Stromal Cells

To understand the role of epidermal cells in the pathogenesis of lichen amyloidosus (LA) and macular amyloidosis (MA).. We carried out immunohistochemical investigations on cytokeratins (CKs) in amyloid deposits in formalin-fixed and paraffin-embedded tissue specimens from eight persons with LA and 12 with MA. The primary antibodies of CK1-8 (AE3), CK10 (DEK-10), CK14 (LL002), CK17 (E3), CK18 (DC10), CK19 (KS19.1), CK5/6/18 (LP34) and CK8/18 (5D3) were used in the study.. In amyloid deposits, immunoreactivity with only two monoclonal antibodies (CK1-8 and CK5/6/18) was observed in 14 cases (eight LA and six MA), confirming the hypothesis that epidermal cells participate in amyloid formation of LA and MA.. All of the CKs detected in amyloid deposits were basic type (type II). It seems plausible either that acidic CKs might be degraded faster than basic types in amyloidogenesis or that paraffin-embedded tissue specimens are less sensitive than frozen tissue sections. The results of our study suggest that when paraffin-embedded specimens are investigated by immunohistochemical methods, CK5 antibody is useful in the diagnosis of LA and MA.

Topics: Adult; Aged; Amyloid; Amyloidosis; Biopsy, Needle; Cohort Studies; Culture Techniques; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Serum Amyloid A Protein; Severity of Illness Index; Skin Diseases

The major component of localized cutaneous amyloids may be derived from cytokeratin (CK). However, the CK profiles of primary cutaneous amyloidosis (PCA) and secondary cutaneous amyloidosis (SCA) remain obscure. Paraffin-embedded sections of skin tissue from 64 patients with PCA, 111 with SCA and 3 with systemic amyloidosis were analyzed immunohistochemically using 12 different polyclonal or monoclonal anti-CK antibodies (34betaE12, MNF116, LP34, AE1/AE3, anti-CK1, CK5, CK6, CK7, CK10, CK14, CK16 and CK17). In addition, frozen skin tissues from 12 patients with PCA were analyzed for comparison with the paraffin-embedded tissue. In all 64 PCA paraffin sections, the amyloid deposits were immunopositive for anti-CK5 antibody and 34betaE12. In all 12 frozen sections of PCA, the amyloid deposits were immunopositive for anti-CK5 antibody, 34betaE12, MNF116 and LP34, and seven (58.3%), three (25%) and one (8.3%) were immunopositive for anti-CK1, CK14, and CK10 antibodies, respectively. In all SCA sections, the amyloid deposits were immunopositive for CK5 and 34betaE12. In addition, MNF116 immunolabeled amyloids of all sections from patients with basal cell carcinoma and trichoepithelioma, and MNF116 and LP34 immunolabeled amyloids of sections from patients with porokeratosis. Our results indicate that CK5 is the major CK present in the amyloid deposits of PCA and SCA, and "amyloid-K" is mainly derived from basal keratinocytes.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Female; Humans; Immunohistochemistry; Keratin-5; Keratinocytes; Keratins; Male; Middle Aged; Skin Diseases

The frequency of amyloid deposits associated with squamous cell carcinoma (SCC) and dysplasia in the oral cavity, pharynx and larynx was examined. In addition, the origin of amyloid proteins by immunohistochemical staining with a panel of anticytokeratin monoclonal antibodies was investigated. Amyloid deposits were found in eight of 73 (11.0%) SCC and one of seven (14.3%) dysplasias in the oral cavity, in eight of 22 (36.4%) SCC and zero of two (0%) dysplasias in the pharynx, and in 22 of 37 (59.5%) SCC and four of 10 (40.0%) dysplasias in the larynx. Eight of 12 different cytokeratin (CK) antibodies reacted with these deposits: 34 beta E12 (CK1, -5, -10, -14) reacted with amyloid deposits in 19 of 19 cases (100%), LL002 (CK14) in eight of 18 cases (44.4%), MNF116 (CK5, -6, -8, -17) in eight of 19 cases (42.1%), D5/16B4 (CK5, -6) in five of 18 cases (27.8%), DE-K10 (CK10) in four of 17 cases (23.5%), RCK108 (CK19) in three of 18 cases (16.7%), 34 beta B4 (CK1) in three of 19 cases (15.8%) and AE8 (CK13) in two of 17 cases (11.8%). These antibodies always reacted with the cytoplasm of squamous cell lesions. Amyloid deposits in two cases contained a CK5 and CK14 pair, and in another two cases they contained both a CK5 and CK14 pair, and a CK1 and CK10 pair. Anti-CK antibodies, including OV-TL12/30 (CK7), c-51 (CK8), DC10 (CK18) and IT-Ks20.8 (CK20) did not react with the amyloid deposits. We conclude that the amyloid deposits associated with SCC or dysplasia in the oral cavity, pharynx or larynx were derived from CK of cancer cells and that some amyloid deposits might be assembled by two or more different CK.

Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms; Precancerous Conditions

The frequency of amyloid deposits in cases of seborrheic keratosis was investigated In addition, the origin of amyloid protein(s) in lichen amyloidosis, macular amyloidosis and seborrheic keratosis was studied by immunohistochemical staining using a panel of anti-cytokeratin (CK) monoclonal antibodies. Amyloid deposits were found in 41 of 327 specimens (12.5%) from 301 cases of seborrheic keratosis. Amyloid deposits in seborrheic keratosis reacted with 6 of 12 CK antibodies and in lichen and macular amyloidosis (20 specimens) reacted with 5 of 12 CK antibodies. In seborrheic keratosis, antibody DE-K10 (labeling CK10) reacted with amyloid in 17 of 36 cases, antibody 34betaE12 (labeling CK1, 5, 10, 14) reacted in 33 of 39 cases, and antibody MNF116 (labeling CK5, 6, 8, 17) reacted in 32 of 35 cases. Among 20 specimens from lichen and macular amyloidosis, the three antibodies reacted with amyloid in the following rates: 1 with antibody DE-K10, all 20 with antibody 34betaE12, and 6 with antibody MNF116. These results suggest that amyloid deposits in seborrheic keratosis and lichen and macular amyloidosis may derive from epidermal cytokeratins.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Female; Humans; Immunohistochemistry; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Skin

To describe a case of posterior polymorphous dystrophy associated with posterior amyloid degeneration of the cornea confirmed histopathologically and immunohistochemically.. An 80-year-old woman with corneal opacities required penetrating keratoplasty. The keratectomy specimen was evaluated by light microscopy and immunohistochemistry.. Microscopic examination of the keratectomy specimen showed scattered fusiform deposits located in the deep corneal stroma. Congo red stains of the fusiform deposits confirmed the diagnosis of amyloidosis. Immunohistochemical stains for cytokeratin (AE1/AE3) showed that the endothelial cells were immunoreactive, confirming the diagnosis of posterior polymorphous dystrophy.. To our knowledge, the association between posterior polymorphous dystrophy and posterior amyloid degeneration has not been reported previously.

Topics: Aged; Aged, 80 and over; Amyloidosis; Corneal Dystrophies, Hereditary; Corneal Opacity; Corneal Stroma; Endothelium, Corneal; Epithelium, Corneal; Female; Humans; Immunoenzyme Techniques; Keratins; Keratoplasty, Penetrating

We report a case of primary localized cutaneous amyloidosis-lichen amyloidosus in a 55-year-old man. Immunohistochemistry using antibodies against cytokeratin and AL immunoglobulins revealed the presence of both components in amyloid foci located subepidermally, mainly in dermal papillae. The results of histochemical reactions confirm the keratin-derived nature of amyloid in primary cutaneous amyloidosis.

Topics: Amyloid; Amyloidosis; Capillaries; Dermis; Humans; Immunoenzyme Techniques; Immunoglobulin Light Chains; Keratins; Male; Middle Aged; Skin; Skin Diseases

The association of porokeratosis with dermal amyloid deposits is extremely rare, only three cases are reported in the literature. We describe a case of disseminated superficial porokeratosis (DSP) with clear histologic evidence of amyloid deposition in the upper dermis. The amyloid was typed with an original immunohistochemical assay based on three anticytokeratin antibodies (MNF 116, CK1, KER B). The epidermal origin of the substance (K amyloid) was demonstrated by its strong positivity for MNF 116 and KER B.

Topics: Aged; Amyloidosis; Humans; Immunohistochemistry; Keratins; Male; Porokeratosis; Skin Diseases

The expression of keratins was investigated immunohistochemically on formalin-fixed and snap-frozen primary cutaneous amyloidosis tissue with a panel of monospecific and polyspecific antikeratin antibodies, with recognized keratins K1, K5, K6, K7, K8, K10, K14, K16, K17, K18 and K19. Amyloid deposits in frozen sections of seven cases of macular amyloidosis and lichen amyloidosus always reacted with antibodies LP34 (labelling K5, K6 and K18), MNF 116 (labelling K5, K6, K8, K10, K17 and K18), and RCK 102 (labelling K5 and K8); frozen sections in one case each of the seven cases also reacted with antibodies LL001 (labelling K14), LP1K (labelling K7 and K17), and LP2K (labelling K19). In formalin-fixed sections of 13 cases of macular amyloidosis and lichen amyloidosus, amyloid deposits were labelled with LP34 in three sections, MNF 116 in four sections, LL020 (labelling keratins K5 and K6) in one section, and LP2K in two sections. In nodular primary cutaneous amyloidosis, amyloid deposits were not labelled with any antikeratin antibodies. These data confirm that amyloid in macular amyloidosis and lichen amyloidosus contains keratin epitopes, and suggests derivation of the fibrillar component from keratin intermediate filaments. Several different keratins appear to undergo conversion to amyloid. LP34, MNF 116 and RCK 102 antibodies, which have in common the labelling of keratin K5, may be useful in the diagnosis of macular and papular amyloidosis with frozen tissue sections.

Topics: Amyloidosis; Antibodies, Antinuclear; Biomarkers; Culture Techniques; Humans; Immunohistochemistry; Keratins; Sensitivity and Specificity; Skin Diseases

Apolipoprotein E (apoE) is one of the amyloid associated proteins that is found in the amyloid plaque of Alzheimer's disease and systemic amyloidosis. ApoE might play an important part in the etiology of Alzheimer's disease by functioning as a "pathologic chaperone" to promote the formation of amyloid filaments. In this study, we investigated whether apoE is associated with amyloid deposits of primary localized cutaneous amyloidosis using immunohistochemistry, immunogold electron microscopy, and immunoblotting. The subjects consisted of 12 patients with lichen amyloidosus and one patient with macular amyloidosis. Light microscopically, amyloid deposits in the dermal papillae were round in shape and stained with Congo red. Immunohistochemically, apoE was detected in amyloid deposits in all the cases examined. Immunogold electron microscopy showed apoE immunoreactivity on the amyloid deposition. Immunoblots of amyloid-positive skin showed 35K and 14K proteins, which were taken to be apoE and its fragment, respectively. In normal skin extract, only the 35K protein was detected by the anti-human apoE. Moreover, the intensity of the amyloid-positive skin sample was stronger than that of the normal skin sample. Monoclonal anti-cytokeratin antibody reacted with the 45K protein of the amyloid-positive skin extract. These results indicate that apoE is a component of primary localized cutaneous amyloidosis, and that it might play an important role in primary localized cutaneous amyloidosis.

Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Antigen-Antibody Reactions; Apolipoproteins E; Female; Humans; Immunoblotting; Immunohistochemistry; Keratins; Lichenoid Eruptions; Male; Microscopy, Electron; Middle Aged; Skin Diseases

Localized amyloidosis of the uterine cervix is a rare entity. Only seven cases have been reported to date, and all were associated with a primary cervical squamous cell carcinoma; immunohistochemical studies proved the amyloid to be composed of cytokeratin, presumably derived from degenerated tumor cells. We report localized cervical amyloidosis producing a 1-cm nodule in a 28-year-old woman in the absence of systemic amyloidosis or a squamous cell carcinoma. Immunohistochemical stains showed the amyloid to be composed of amyloid-associated protein, a protein produced in chronic inflammatory conditions.

Topics: Adult; Amyloid; Amyloidosis; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; Keratins; Uterine Cervical Diseases

Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes.. Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA.. We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment.. In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective.. LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Amyloid; Amyloidosis; Antipruritics; Chronic Disease; Collagen; Disease; Female; Histamine H1 Antagonists; Humans; Keratinocytes; Keratins; Keratosis; Leg Dermatoses; Male; Middle Aged; Necrosis; Neurodermatitis; Pruritus; Remission Induction; Skin; Skin Diseases

Eosinophilic hyaline inclusions were consistently seen in the perinuclear cytoplasm of suprabasal keratinocytes in lichen amyloidosus. The inclusions, negative with amyloid staining, were immunoreactive for ubiquitin and cytokeratin, and ultrastructurally showed aggregations of fine filaments of two sizes (central thin and peripheral thick). The thin filaments were the main component in the upper epidermal layer. Four monoclonal antibodies (AE1, AE3, KL1 and CAM5.2) and one antiserum (WSS) were used for characterizing cytokeratin expression. The AE1 antibody normally stained the basal cells, but in lichen amyloidosus basal staining mostly disappeared. Instead, groups of suprabasal keratinocytes were labeled, with AE1-reactive inclusions distributed therein. In contrast, the KL1 antibody, showing suprabasal staining, failed to react with the inclusions. The inclusions were weakly reactive with the AE3 and WSS antibodies, which stained all keratinocytes. The CAM5.2 antibody was unreactive. The subepidermal amyloid deposits were negative with all the antibodies. The inclusions were ubiquitinated especially in the granular layer. Immunoelectron microscopy disclosed that ubiquitin was more densely localized in the thin filaments than in the thick ones. This indicated that cytokeratin expression and metabolism are altered in the affected epidermis, and that ubiquitin functions in the process of degradation of abnormal cytokeratin filaments.

Topics: Adolescent; Adult; Aged; Amyloidosis; Antibodies, Monoclonal; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Inclusion Bodies; Keratinocytes; Keratins; Lichen Planus; Male; Microscopy, Immunoelectron; Middle Aged; Skin; Ubiquitins

Topics: Adult; Amyloidosis; Female; Humans; Immunohistochemistry; Keratins; Lichen Planus; Macula Lutea; Male; Middle Aged; Retinal Diseases; Skin

Nail pathology shares some common features with skin pathology, but it also has its own peculiar aspects. The anatomical and physiological characteristics of the nail unit probably play a major role in determining these pathological differences. Although the presence of keratohyaline granules is a normal feature of the skin, there is no granular layer in the normal nail matrix. As a consequence, nail matrix hypergranulosis should be considered a separate entity from skin hypergranulosis. In our review of 150 longitudinal nail biopsy specimens, keratohyaline granules were seen in the nail matrix of 24 cases of lichen planus, 29 cases of spongiotic trachyonychia, 10 cases of psoriasis, and three cases of Hallopeau acrodermatitis. In all cases, the presence of keratohyaline granules was associated with the absence of the normal keratogenous zone. Similar nail matrix features were detectable in three cases of malignant melanoma, two cases of primary systemic amyloidosis, and one case of histiocytoid hemangioma compressing the nail matrix. Our data suggest that inflammatory and compressive insults to the nail matrix cause both disappearance of the keratogenous zone and matrix keratinization with the formation of keratohyaline granules. Skin hypergranulosis reflects a hyperplasia of a normal skin component. In the nail matrix, however, hypergranulosis represents the appearance of structures not normally present. Nail matrix hypergranulosis should be considered a pattern of nail matrix reaction to different inflammatory insults. It is therefore more analogous to epidermal parakeratosis than to epidermal hypergranulosis.

Topics: Acrodermatitis; Amyloidosis; Biopsy; Epidermis; Epithelium; Hemangioma; Humans; Hyalin; Hyperplasia; Keratins; Keratosis; Lichen Planus; Melanoma; Nail Diseases; Nails; Onychomycosis; Psoriasis

Fifty-one non-neoplastic human pituitary glands, including examples with Crooke's hyalinization or amyloidosis, were examined by an immunoperoxidase method using antibodies to keratin, vimentin, neurofilaments (NFs), glial fibrillary acidic protein (GFAP), desmin, actin, S-100 protein and a variety of pituitary hormones. It was confirmed that most of the epithelial cells in the pituitary gland express keratin immunoreactivity. These cells included endocrine cells in the anterior lobe, endocrine cells and squamous metaplastic cells in the pars tuberalis, columnar and ciliated epithelia forming follicular structures and salivary-type epithelium in the pars intermedia, and anterior lobe cells infiltrating the posterior lobe. This study also demonstrated that keratin and NFs may be co-expressed in endocrine cells in the pituitary anterior lobe, that keratin, vimentin and GFAP may be co-expressed in the epithelial cells forming cyst-like follicle in the pars intermedia, and that vimentin and GFAP may be co-expressed in folliculo-stellate cells and pituicytes. In addition, the GFAP and S-100 protein-negative high columnar epithelium in the pars intermedia tended to be positive for adrenocorticotropic hormone and melanocyte stimulating hormone, while the low columnar epithelium with the co-expression of GFAP and S-100 protein was negative for pituitary hormones.

Topics: Amyloidosis; Antibody Specificity; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Pituitary Gland

We present a patient with lichen amyloidosus on the ears and macular amyloidosis on the back. These diagnoses were supported by histological, histochemical and immunohistochemical studies. This is to the best of our knowledge the first reported case of a biphasic form of amyloidosis whose lichenoid counterpart consists of papules on the ears. This suggests that primary cutaneous localized amyloidosis may have peculiar clinical manifestations depending on the location of the lesion.

Topics: Amyloidosis; Ear Diseases; Ear, External; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Skin Diseases

Immunohistochemical staining properties of amyloids with anti-keratin antibodies were investigated using an avidin-biotin-peroxidase complex (ABC) system on formalin-fixed, paraffin-embedded sections. Anti-keratin antibody EAB-903 which recognize 66K and 57K daltons keratin peptides reacted with amyloid deposits in both lichen amyloidosus (LA) and macular amyloidosis (MA), but did not react with either primary systemic amyloidosis (AL), secondary systemic amyloidosis (AA) or heredofamilial amyloid polyneuropathy (AF). However, anti-keratin antibodies EAB-904 and MAK-6 did not react with any types of amyloids. These results suggested that immunohistochemical staining with anti-keratin antibody EAB-903 using formalin-fixed, paraffin-embedded sections appeared to be a useful method in making differential diagnosis of primary localized cutaneous amyloidosis (AD).

Topics: Amyloid; Amyloidosis; Antibodies; Formaldehyde; Histological Techniques; Humans; Immunohistochemistry; Keratins; Paraffin; Reference Values; Skin; Staining and Labeling

In order to characterize immunoglobulins found on amyloid deposits of lichen amyloidosus and macular amyloidosis, and elution from cryostat sections was performed with citrate buffer, glycine buffer, NaCl, and PBS. Resulting eluates (mainly IgG) were examined with dot immunoblotting and SDS-PAGE immunoblotting and were found to react with the human epidermal keratin of 50 and 67 kD. Antikeratin autoantibody activities in normal murine and human sera were examined using a dot immunoblotting assay. In murine sera, titers of IgG and IgM autoantibodies were higher in older mice. The human cord blood showed significantly lower IgM autoantibody titers, whereas IgG antibody titers showed no significant differences from adults' sera, probably due to the permeability of IgG through the placental barrier. A stronger antibody activity in older individuals was thought to be due to the repeated exposures to keratin proteins derived from apoptotic keratinocytes. Sera from lichen amyloidosus and macular amyloidosis patients did not show any difference from normal controls in their antikeratin titers. It was concluded that the patients with lichenoid or macular amyloidosis are capable of producing a normal level of antikeratin autoantibodies. However, the removal of opsonized keratin-type amyloid from the skin is slow or deficient due to as yet unknown factors.

Topics: Amyloid; Amyloidosis; Animals; Autoantibodies; Fluorescent Antibody Technique; Humans; Immunoblotting; Immunoglobulin G; Immunoglobulin M; Keratins; Mice

Topics: Aged; Amyloid; Amyloidosis; Antibodies, Monoclonal; Antibody Specificity; Humans; Immunohistochemistry; Keratins; Male; Skin; Skin Diseases

In lichen amyloidosus (LA) and macular amyloidosis (MA), small amyloid deposits occur in the upper papillary dermis. Previous electron-microscopic studies have indicated an epidermal origin of the amyloid, where degenerating keratinocytes drop into the dermis and undergo transformation to amyloid. While this mechanism seems possible at least in MA, we suggest an alternative pathogenetic pathway in LA, in which amyloid fibrils seem to form on the dermal surface of living basal keratinocytes. It is possible that the different morphology of the amyloid in LA and MA is explained by partially different pathogenetic mechanisms although the amyloid in both conditions may be chemically closely related.

Topics: Amyloid; Amyloidosis; Epidermis; Humans; Keratins; Microscopy, Electron

Topics: Aged; Amyloid; Amyloidosis; Anal Canal; Antibodies, Monoclonal; Coloring Agents; Humans; Keratins; Male; Organic Chemicals; Sacrococcygeal Region; Skin; Skin Diseases; Staining and Labeling

The ultrastructure of six cases of lichen amyloidosus was studied with special attention to epidermal keratinocytes and the role of tonofilaments as precursors of fibrils of amyloid. Through the process of apoptosis, keratinocytes undergo degeneration and become filamentous cells and then filamentous masses or Civatte bodies. These bodies then drop into the dermis through a damaged basement membrane. In the papillary dermis, islands of amyloid become closely associated with Civatte bodies. In some cases, conversion to straight nonbranching filaments, characteristic of fibrils of amyloid, was found within whorled, densely packed filamentous masses. The transformation into fibrils of amyloid was not observed in keratinocytes or Civatte bodies situated in the epidermis. This final step of conversion may be aided by dermal fibroblasts that are frequently lodged around deposits of amyloid.

Topics: Adult; Amyloidosis; Female; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases

Topics: Amyloid; Amyloidosis; Antibodies; Fluorescent Antibody Technique; Humans; Keratins; Skin Diseases; Staining and Labeling

The authors have used 5 different monoclonal antikeratin antibodies to study the antigenic profiles of cytoid bodies and skin-limited amyloids. Monoclonal antibodies AE1 (which stains the basal cell layer in normal human epidermis), AE2 (suprabasal layers), AE3 (whole epidermis), EKH4 (lower 2-3 layers), and EKH1 (recognizes all classes of intermediate filaments) were used to stain frozen skin sections by the indirect immunofluorescent or indirect immunoperoxidase technique. Cytoid bodies in lichen planus (LP) and discoid lupus erythematosus (DLE) were strongly stained with AE1, AE3, EKH4, and EKH1 antibodies but were negative with AE2. In contrast, amyloids in lichen amyloidosus and macular amyloidosis were stained strongly with EKH4 but only weakly or not at all with AE1, AE2, AE3, and EKH1. Amyloid associated with epithelial tumors showed closer immunologic profiles to cytoid body. These findings suggest that epidermal keratins are the major precursor substance of skin-limited amyloids as well as cytoid bodies in LP and DLE. Sequential changes in antigenic profiles from basal cells to amyloids through cytoid bodies further suggest that cytoid bodies may represent one of the precursor substances of skin-limited amyloids.

Topics: Amyloid; Amyloidosis; Antibodies, Monoclonal; Carcinoma, Basal Cell; Fluorescent Antibody Technique; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Skin Diseases; Skin Neoplasms; Staining and Labeling

Thirty-one cases of primary cutaneous amyloidosis were studied by the immunoperoxidase technique (PAP method) employing anti-keratin antibodies. All specimens were examined using consecutive paraffin sections to confirm the correspondence between amyloid existing area and reactive sites. All of the sections examined were non-reactive in amyloid deposited sites whereas the epidermis always showed strong reaction with anti-keratin antibodies.

Topics: Amyloid; Amyloidosis; Antibodies; Humans; Immunoenzyme Techniques; Keratins; Skin

Epidermal keratin was extracted and antibody against this protein was produced in rabbits. Various forms of organ-limited cutaneous amyloidosis (lichenoid, macular, and nodular amyloidosis, and basal cell epithelioma) and primary systemic amyloidosis were immunohistochemically examined to test the identity between epidermal keratin and skin amyloid. Amyloids in lichenoid and macular amyloidoses, and in basal cell epithelioma had an identical antigenicity with epidermal keratin, whereas amyloids in nodular amyloidosis and systemic amyloidosis did not have this identity. In addition, amyloid in lichen amyloidosis contained disulfide bonds as in keratin. Connective tissue components including filaments of fibroblasts and vascular endothelial cells did not react with this antikeratin antibody. It was concluded that at least some of the amyloid substance in organ-limited cutaneous amyloidosis is derived from degenerated epidermal keratinocytes through filamentous degeneration or apoptosis.

Topics: Amyloid; Amyloidosis; Epitopes; Fluorescent Antibody Technique; Humans; Keratins; Skin; Skin Diseases

Lichen amyloidosus (LA) and macular amyloidosis (MA) are two forms of localized cutaneous amyloidosis in which the amyloid occurs as larger and smaller deposits respectively in the papillary dermis. The histogenesis of the amyloid of these conditions is unknown. By using an indirect immunofluorescence technique we showed that LA and MA do not react with antibodies against different previously characterized amyloid fibril proteins. These results indicate that the amyloid of LA and MA is different from other known types of amyloid. Protein AP, which was demonstrated in amyloid of MA and LA, is known to be present in all forms of amyloid and is of unknown significance. Antiserum against keratin did not react with the larger homogeneous amyloid bodies, but showed a weak reaction with some small deposits. Histochemical staining failed to show keratin in any of the tissues containing LA or MA.

Topics: Adult; Aged; Amyloid; Amyloidosis; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Skin; Skin Diseases

Topics: Amyloid; Amyloidosis; Antibodies; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Skin Diseases

A case of localized cutaneous amyloidosis which developed after a lichen planus-like skin reaction is reported. The amyloid consisted of amyloid fibrils enveloped by heparan sulphate granules. These amyloid fibrils reacted to anti-human keratin antibody, indicating an epidermal origin for the fibrils.

Topics: Aged; Amyloid; Amyloidosis; Antibodies; Heparitin Sulfate; Humans; Keratins; Male; Skin; Skin Diseases

Amyloid of localized cutaneous amyloidosis and systemic amyloidosis were subjected to study with an indirect immunofluorescence technique using anti-keratin antiserum. Anti-keratin antiserum was prepared ad modum Sun & Green. Amyloid of localized cutaneous amyloidosis was positively stained for the antiserum, whereas amyloid of systemic amyloidosis (primary and multiple myeloma-associated) was negative. There was no difference between primary localized cutaneous amyloidosis (lichen amyloidosus and macular amyloidosis) and secondary localized cutaneous amyloidosis (amyloidosis associated with skin tumor). These results indicate that amyloid of localized cutaneous amyloidosis contains components derived from epidermal fibrous protein, probably tonofilaments of keratinocytes.

Topics: Amyloid; Amyloidosis; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Multiple Myeloma; Skin; Skin Diseases

Topics: Amyloidosis; Antibodies; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Keratins

Skin specimens obtained from two cases of primary localized cutaneous amyloidosis (PLCA) were subjected to study with an indirect immunofluorescence technique using anti-keratin antibody. Distinct fluorescence was observed in stratum corneum, and in spinous and basal cells of the epidermis and also in amyloid masses located in the upper dermis. These results appear to indicate that keratinous protein is one of the constituents of amyloid masses of cutaneous amyloidosis.

Topics: Amyloidosis; Antibodies; Fluorescent Antibody Technique; Humans; Keratins; Skin

Topics: Amyloid; Amyloidosis; Carcinoma, Basal Cell; Epidermis; Fibroblasts; Histiocytes; Humans; Keratins; Psoriasis; Skin

Two cases of lichen amyloidosus and 8 cases of macular amyloidosis were examined by electron microscopy. Epidermal keratinocytes showed variable degrees of focal degeneration in the basal or lower Malpighian layer. The primary change was seen in cells which contain fibrillar (30 nm in thickness) cytoplasmic inclusion. The following developments seemed to lead to filamentous degeneration (colloid bodies): (1) aggregation of tonofilaments within the granular or fibrillar cytoplasm, (2) filamentous cells, which are composed of bundles of 7-nm thick filaments surrounded by cell membrane and desmosomes, and (3) filamentous masses composed of bundles or whorls of tightly packed 7-nm thick filaments in the intercellular spaces. At the dermo-epidermal junction, some of the filamentous masses were surrounded by the basal lamina of the epidermis and others were dropping into the dermis. Occasionally, loosened filaments (similar to amyloid filaments) were about to drop into the dermis. Early formation of amyloid islands consisted of electron-dense and electron-light parts. They were located directly beneath the epidermis. In the deeper postion of the papillary dermis and in the upper reticular dermis, the majority were electron-light masses. Electron dense parts were the densely packed 7-nm thick filaments, whereas electron-light parts were the typical straight amyloid filaments. Small tubular filaments were seen in common in the filamentous cells, filamentous masses, and amyloid islands. It is concluded that some of the amyloid substance in primary localized forms of cutaneous amyloidoses derive from the epidermal cells through filamentous degeneration.

Topics: Adult; Amyloid; Amyloidosis; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Skin Diseases; Time Factors

Topics: Amyloid; Amyloidosis; Cytoplasm; Fibroblasts; Humans; Keratins; Leg; Male; Middle Aged; Skin; Skin Diseases

Topics: Adult; Aged; Amyloid; Amyloidosis; Collagen; Diagnosis, Differential; Female; Forearm; Humans; Keratins; Leg Dermatoses; Lichen Planus; Lipidoses; Male; Melanins; Middle Aged; Pruritus; Skin; Skin Diseases; Skin Neoplasms; Staining and Labeling