Identifying the potential origin of mucin in primary cutaneous mucinoses-A retrospective study and analysis using histopathology and multiplex fluorescence staining.

BACKGROUND: Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits. OBJECTIVES: A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a single-cell level. MATERIAL AND METHODS: Patients diagnosed with PCM between 2010 and 2020 at our department were included in this study. Biopsy specimens were stained using conventional mucin stains (Alcian blue, PAS) and MUC1 immunohistochemical staining. Multiplex fluorescence staining (MFS) was used to investigate which cells were associated with MUC1 expression in select cases. RESULTS: Thirty-one patients with PCM were included, 14 with follicular mucinosis (FM), 8 with reticular erythematous mucinosis, 2 with scleredema, 6 with pretibial myxedema and one patient with lichen myxedematosus. In all 31 specimens, mucin stained positive for Alcian blue and negative for PAS. In FM, mucin deposition was exclusively found in hair follicles and sebaceous glands. None of the other entities showed mucin deposits in follicular epithelial structures. Using MFS, all cases showed CD4+ and CD8+ T cells, tissue histiocytes, fibroblasts and pan-cytokeratin+ cells. These cells expressed MUC1 at different intensities. MUC1 expression in tissue histiocytes, fibroblasts, CD4+ and CD8+ T cells, and follicular epithelial cells of FM was significantly higher than the same cell types in the dermal mucinoses (p < 0.001). CD8+ T cells were significantly more involved in expression of MUC1 than all other analysed cell types in FM. This finding was also significant in comparison with dermal mucinoses. CONCLUSION: Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins.

Oral focal mucinosis: A multi-institutional study and literature review.

BACKGROUND: Oral focal mucinosis (OFM) is a rare benign condition of unknown etiology, considered the oral counterpart of cutaneous focal mucinosis. We report the clinicopathologic features of 21 cases of OFM in conjunction with a review of the literature. METHODS: Clinical data were collected from the records of five oral and maxillofacial pathology services. All cases were evaluated by hematoxylin and eosin staining, histochemistry, and immunohistochemistry (vimentin, S-100, α-SMA, CD34, and mast cell). RESULTS: The series comprised 14 females (66.7%) and seven males (33.3%), with a mean age of 48.2 ± 20.7 years (range: 8-77 years) and a 2:1 female-to-male ratio. Most of the lesions affected the gingiva (n = 6, 28.6%) and presented clinically as asymptomatic sessile or pedunculated nodules with fibrous or hyperplasic appearance. All cases were negative for S-100 protein, CD34, and α-SMA and positive for Alcian blue staining. Conservative surgical excision was the treatment in all cases, and there was only one recurrence. CONCLUSION: OFM is a rare benign disorder that is often clinically misdiagnosed as reactive lesions or benign proliferative processes. Dermatologists and pathologists should consider OFM in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located in the gingiva.

Mycosis fungoides with epidermal mucinosis: a variant of mycosis fungoides with a spongiosis-like pattern.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) has classically relied on the presence of atypical epidermotropic T-lymphocytes predominating over spongiosis. However, in some cases of MF, prominent epidermal mucinosis in a spongiosis-like pattern mimics a spongiotic dermatitis. To our knowledge, only one series in the literature has thus far recognized the presence of epidermal mucinosis in MF. METHODS: We evaluated 30 skin biopsies from 18 patients with the clinical diagnosis of MF, which fulfilled all histopathologic criteria for patch- or plaque-stage MF, but also showed epidermal mucinosis in a spongiosis-like pattern. A total of 15 specimens were studied by immunohistochemistry, and seven were tested for T-cell receptor (TCR) gene rearrangements. Twenty biopsies of spongiotic dermatitides were included as controls. RESULTS: We confirmed the presence of epidermal mucinosis in all 30 cases of MF with a spongiosis-like pattern based on histopathologic criteria and the colloidal iron stain for mucin. Immunohistochemistry in 15 specimens showed significant loss of pan-T-cell antigens CD5 (10/15) and CD7 (14/15); and TCR clonality was detected in 7 specimens from 6 patients, supporting the diagnosis of MF. CONCLUSIONS: We report helpful histopathologic criteria for distinguishing MF with epidermal mucinosis in a spongiosis-like pattern from spongiotic dermatitis.

Reticular erythematous mucinosis: histopathological and immunohistochemical features of 25 patients compared with 25 cases of lupus erythematosus tumidus.

BACKGROUND AND OBJECTIVES: Reticular erythematous mucinosis (REM) and lupus erythematosus tumidus (LET) share similarities. However, to our knowledge no study extensively compared the histological features of these two conditions. The aim of this study is to compare the histological and immunohistochemical features of REM and LET. METHODS: We evaluated epidermal thickness, hyperkeratosis, dermo-epidermal junction changes, interstitial mucin deposition, vessel dilatation and pattern, type and density of the inflammatory infiltrate in 25 cases of REM and LET. Anti-CD3, anti-CD20, anti-CD68, anti-CD4, anti-CD8, anti-CD123, anti-CD2AP, anti-IgG and anti-C3 antibodies were tested in a subset of patients. RESULTS: Both diseases are characterized by perivascular dermal infiltrates of lymphocytes mainly CD4+ positive and increased dermal mucin. However, REM tended to show more scattered and more superficial lymphocytes with more superficial mucin and to have less frequent immunoglobulin and complement depositions along the dermo-epidermal junction. Plasmacytoid dendritic cells (PDCs) were less represented in REM, and were mainly found as single cells differently from LET. CONCLUSIONS: REM and LET present some differences in the infiltrate, including PDCs, the mucin deposition and the immunoreactant deposition at the dermo-epidermal junction that justify the distinction of the two diseases and suggest different pathogenetic mechanisms.

Ossifying fibromyxoid tumor of the breast mimicking fibroadenoma: a case report and differential diagnoses.

An 80-year-old woman presented with a palpable mass in the right breast. Mammographic findings were consistent with calcified fibroadenoma. An ultrasound was performed that showed a solid nodule with peripheral calcification. A core biopsy was obtained that revealed a spindle cell proliferation with a shell of mature bone. The histologic features, in combination with immunohistochemical studies, were those of an ossifying fibromyxoid tumor. Complete excision of the specimen further confirmed the diagnosis. To the best of our knowledge, this is the first reported case of ossifying fibromyxoid tumor occurring in the breast. We review the current literature on ossifying fibromyxoid tumor and discuss the differential diagnoses when confronted with bland spindle cells on a core biopsy of the breast.

Nodular lesions of self-healing juvenile cutaneous mucinosis: a pitfall!

Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder of unknown origin, which occurs in children in good health. It is characterized by the multiplication of transient cutaneous papules and nodules, mainly located on the head and periarticular areas that spontaneously resolve. Histological features of SHJCM have been well described; therefore, the diagnosis is usually made easily when papules are biopsied. We report a series of 3 new cases of SHJCM presenting mainly with nodular lesions. Histological examination of these nodules showed either lesions consistent with nodular or proliferative fasciitis or nonspecific panniculitis. Mucinous deposits were present but often inconspicuous, so could be disregarded. We wanted to emphasize this misleading presentation because a biopsy for histological examination is always mandatory in cases of proliferating nodules to rule out malignant tumors. Therefore, the diagnosis always requires discussion between pathologists and clinicians to rapidly reassure the parents and avoid inappropriate therapy.

Hereditary progressive mucinous histiocytosis: first report in a male patient.

Progressive mucinous histiocytosis is a very rare, benign, non-Langerhans' cell histiocytosis limited to the skin. In total ten patients (all women) in four families and three sporadic cases have been reported. We report here the first published case of a male patient with progressive mucinous histiocytosis. The multiple red papules on the scalp and forearms were asymptomatic and had slowly increased over approximately the past 20 years. The patient's mother had similar lesions. Histological examination revealed nodules in the dermis with histiocytes and mucin deposition. The histiocytes stained positively with CD31 and negative with CD34, CAM 5.2, PGM-1 and factor XIIIa. Ultrastructurally, the histiocytes showed numerous circular myelin bodies and zebra bodies reminiscent of those seen in lysosomal storage diseases. The genetic transmission of hereditary progressive mucinous histiocytosis remains unclear; we assume an autosomal dominant transmission with some hormonal factor that makes hereditary progressive mucinous histiocytosis more likely in women.

Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum.

BACKGROUND: Dermal mucin is an amorphous gelatinous substance composed primarily of hyaluronan (HA) and sulphated glycosaminoglycans (GAGs). In primary cutaneous mucinosis, accumulation of mucin is a characteristic feature of lichen myxoedematosus, scleromyxoedema and reticular erythematous mucinosis. Secondary mucinoses are disorders where mucin deposition is an additional finding, and deposition is associated with lupus erythematosus, dermatomyositis, scleroderma and granuloma annulare. The underlying cause of the abnormal mucin deposition is unknown. An increasing number of cases of a fibromucinous scleromyxoedema-like disorder associated with renal dysfunction, recently termed nephrogenic fibrosing dermopathy (NFD), is being reported. OBJECTIVES: To examine the synthesis of sulphated GAGs and HA by fibroblasts derived from uninvolved and involved skin of a patient with dermatomyositis and two patients with NFD, and the effect of patient serum. METHODS: GAGs were quantified by a radiometric assay and HA was determined by an enzyme-linked HA-binding protein assay. RESULTS: We found that fibroblasts derived from active lesions of NFD synthesize elevated levels of GAGs, and in particular HA, compared with normal controls, while serum from the patient with dermatomyositis and the two patients with NFD stimulates GAG synthesis, including HA synthesis, by both control and patient fibroblasts. CONCLUSIONS: Fibroblasts from patients with active NFD are either activated to synthesize elevated levels of HA or contain another cell type, possibly derived from circulating fibrocytes. In both disorders, there is additionally a serum-derived factor that stimulates production of sulphated GAGs and HA by fibroblasts.

Two sporadic cases of adult-onset progressive mucinous histiocytosis.

Progressive mucinous histiocytosis is a rare, benign, non-Langerhans' cell histiocytosis limited to the skin. Ten cases--all women--in four families and one sporadic case have been described in the literature. The disorder usually begins in childhood and progresses slowly. We report two sporadic cases of adult-onset progressive mucinous histiocytosis in unrelated African-American women, aged 48 and 55 years, respectively, who developed red-brown and flesh-coloured, asymptomatic papules on the face, the arms and the legs without truncal, mucosal or visceral involvement. The lesions showed no spontaneous regression. Both patients lacked associated systemic symptoms, including polyuria, polydipsia or seizures. There was no underlying hyperlipidaemia, paraproteinaemia or lymphoproliferative disease. No family history of similar lesions could be identified. Light microscopy revealed dermal proliferation of spindle-shaped histiocytes with abundant mucin deposition. Electron microscopy demonstrated a high number of myelin figures or zebra bodies in the cytoplasm of histiocytes. On immunohistochemistry, positive staining with macrophage markers--CD68, HAM56 and lysozyme--and factor XIIIa, a transglutaminase present in dermal dendrocytes, and negative staining with Langerhans' cell markers--CD1a and S100--and CD34, a marker present in dermal dendritic cells derived from uncommitted mesenchymal cells, were observed.

Cutaneous mucinoses: microscopic criteria for diagnosis.

The clinical aspects and the histologic features of cutaneous mucinoses have been reviewed and their classification updated. Cutaneous mucinoses are divided into distinctive (primary) cutaneous mucinoses in which the mucin deposit is the main histologic feature resulting in clinically distinctive lesions, and disorders associated with histologic mucin deposition as an additional finding (secondary mucinoses). The former are further divided into degenerative-inflammatory mucinoses, which may be either dermal or follicular, and into neoplastic-hamartomatous mucinoses. Histopathologic diagnosis is particularly difficult for dermal mucinoses and requires clinicopathologic correlation. Three histologic clues, namely the pattern of mucin distribution (diffuse or focal), the level of mucin deposit in the dermis and some additional findings may help diagnosis. Follicular mucinoses have the easiest pattern to recognize histologically, but the distinction between Pinkus' follicular mucinosis and follicular mucinosis with mycosis fungoides is very difficult.Lastly, neoplastic-hamartomatous cutaneous mucinoses include mucinous nevus, a benign hamartoma, and myxoma, which is a benign tumor to be differentiated from reactive cutaneous focal mucinosis.

Solitary subcutaneous mucinosis surrounded by bizarre-shaped, factor XIIIa-positive cells with intranuclear vacuoles.

We describe a subcutaneous mucinosis developing in the right cheek of a 38-year-old man. Histologic examination revealed bipolar fibroblast-like cells embedded in a well demarcated mucinous stroma in the subcutis without a manifest reticulin network. In addition, bizarre, sometimes multinucleate, cells with intranuclear vacuoles were found at the periphery of the mucinous stroma. Immunohistologically, both the bipolar fibroblastic cells and bizarre-shaped cells were positive for vimentin, but were negative for smooth muscle A-actin, desmin, CD34, S100, trypsin, or chymotrypsin. However, the latter reacted to anti-factor XIIIa antibody, suggesting that they are derived from dermal dendritic cells. We think that this solitary subcutaneous mucinosis is a unique variant of cutaneous focal mucinosis, because neither a reticulin network nor reactivity to anti-smooth muscle A-actin antibody were demonstrable.

Fatal scleromyxedema: report of a case and review of the literature.

Scleromyxedema is a rare fibromucinous connective tissue that can be associated with systemic changes, such as myopathy, neurologic defects, esophageal dysmotility, paraproteinemia, and restrictive lung disease. We describe a fatal case of scleromyxedema in which neurologic, cardiac, gastrointestinal, and muscle changes were present. At autopsy, mucin was found in the papillary dermis of skin and in coronary and pulmonary vessels, but was absent from the brain, kidneys, heart, gastrointestinal tract, esophagus, liver, thyroid, lymph nodes, bone marrow, and pancreas. Because the pathogenesis of scleromyxedema may not always be attributable to mucin deposition, the role of circulating factors in the development of systemic manifestations warrants further investigation.

Type I and type III collagens in cutaneous mucinosis.

Cutaneous mucinoses are a heterogeneous group of diseases characterized by the focal or diffuse dermal deposition of glycosaminoglycans. The histopathologic examination of many cutaneous mucinoses reveals that the collagen fibers are fragmented. We wanted to characterize the type I (COL1) and type III (COL3) collagen distribution in skin biopsy specimens of patients with cutaneous mucinosis. The diagnosis of mucinosis was based on a modification of the classification by Rongioletti and Rebora: four patients had familial papulonodular mucinosis: four had papular mucinosis, one of which was associated with myxedema and one had scleromyxedema; and one had focal mucinosis. We performed anti-type I and type III collagens immunolabeling on frozen sections. Immunofluorescence for COL1 was increased in the superficial dermis of 2/4 familial papulonodular mucinosis, in 5/5 of papular mucinosis, and in scleromyxedema and focal mucinosis cases. The mid-dermis showed intense staining for COL1 at the periphery of collagen bundles and, in three cases of familial papulonodular mucinosis and two cases of papular mucinosis, a lacy appearance. The superficial dermis of familial papulonodular mucinosis specimens and of papular mucinosis + myxedema, scleromyxedema, and focal mucinosis specimens had decreased COL3 staining. The mid-dermis showed a more prominent fibrillar staining at the periphery of the collagen bundles, and two cases of papular mucinosis showed intense labeling for COL3. Both COL1 and COL3 distributions are altered in cutaneous mucinosis. An intense labeling with COL1 is predominantly found in the superficial layer of cutaneous mucinosis. Cases of FTP revealed decreased COL3 reactivity at the superficial layer.

Polyarthritis with cutaneous mucinosis and intrasynovial mucin deposits.

We report the first case of cutaneous and articular mucinosis with presence of mucin deposits within the synovium in an HIV-positive patients. Presentation was asymmetric polyarthritis, and subcutaneous nodules developed two months later. Treatment was with hydroxychloroquine. The outcome of both the skin and joint lesions was favourable.

Reticular erythematous mucinosis syndrome: glycosaminoglycan synthesis by fibroblasts and abnormal response to interleukin-1 beta.

BACKGROUND: Reticular erythematous mucinosis (REM) syndrome is characterized by an accumulation of mucin in the dermis. OBJECTIVE: To elucidate the mechanism of mucin deposition, the response of REM syndrome fibroblasts to various exogenous factors was studied. METHOD: REM and control fibroblasts were treated with potent modulators including tumor necrosis factor-alpha, basic fibroblast growth factor, interferon-gamma, transforming growth factor-beta 1 and interleukin-1 alpha (IL-1 alpha) and -4. RESULTS: IL-1 beta failed to stimulate glycosaminoglycan synthesis in REM fibroblasts whereas it stimulated glycosaminoglycan synthesis up to 6-fold in control fibroblasts. The stimulation of glycosaminoglycan was caused largely by a comparable increase in hyaluronic acid. CONCLUSION: These results suggest that the patient fibroblasts exhibit an abnormal response to stimulation by exogenous IL-1 beta and that IL- 1 beta may be involved in the abnormal hyaluronic acid metabolism in REM syndrome.