Proliferation of reactive and neoplastic human tissue mast cells. An immunohistochemical study using the antibody PC10 (anti-PCNA)

Studies on the proliferative compartment of human tissue mast cells (MCs) and their tumours (mastocytosis) have not been performed. We have used the monoclonal antibody PC 10 to study MCs in reactive or hyperplastic states (chronic non-specific lymphadenitis, n = 10; benign and malignant solid tumours, n = 5) and in the various subtypes of mastocytosis (urticaria pigmentosa, n = 22; solitary mastocytoma of the skin, n = 7; systemic mastocytosis; n = 8; malignant mastocytosis, n = 4). The identification of PC10-positive MC nuclei was achieved by double staining. We found no PC10-positive MCs in reactive or hyperplastic states, or in 14 of 22 cases of urticaria pigmentosa. PC 10-positive MCs could be identified in all other mastocytoses but mostly in very low numbers. The mean percentages of PC10-positive MCs amounted to 0.5 in eight positive cases of urticaria pigmentosa, 1.2 in mastocytoma, 0.7 in sytemic mastocytosis, and 4.0 in malignant mastocytosis. The difference between the latter form of mastocytosis and each of the other subtypes proved to be significant (P<0.05). The very smali proliferative compartment in the cutaneous and sytemic variants of mastocytosis is in accord with their favourable prognosis Most of the patients with systemic mastocytosis in the present study are all alive and well up to 12 years after diagnosis. In contrast, most of the patients with malignant mastocytosis died within 1 year of diagnosis.     

Mast-cell phenotype in indolent forms of mastocytosis. Ultrastructural features, fluorescence detection of avidin binding, and immunofluorescent determination of chymase, tryptase, and carboxypeptidase.

The factor(s) that causes excessive mast cell (MC) proliferation in indolent forms of mastocytosis is not known, nor is it known whether that proliferation is a regulated clonal expansion or merely a non-neoplastic hyperplasia. Human MCs display phenotypes that depend on the microenvironment. Thus, if the phenotype of MCs in mastocytosis lesions is determined to be abnormal for that tissue site (and therefore the MCs are refractory to microenvironmental signals) then a clonal process would be suggested. The authors determined the phenotypes of MCs from the lesional skin of 17 patients with indolent mastocytosis and the bone marrows of 9 patients. They compared them with the phenotypes of MCs from the lesional skin of 8 patients with various dermatitides, the skin of 2 patients with idiopathic anaphylaxis, and the breast skin of 15 control patients. MCs from all the skin specimens showed the characteristic skin MC phenotype, with predominantly scroll-poor granules by ultrastructure and containing tryptase and chymase by immunofluorescence detection (the MCTC immunophenotype). The skin MCs of each patient bound avidin and contained carboxypeptidase by immunofluorescence detection. MCs from the bone marrow of patients with indolent mastocytosis, the source of progenitors, also showed the scroll-poor and MCTC phenotypes. These findings do not support an unregulated clonal expansion in indolent forms of mastocytosis. They are consistent with a non-neoplastic hyperplasia or possibly a clonal process in which MCs remain responsive to microenvironmental regulation.     

Mastocytosis, classification, biological diagnosis and therapy

In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic none MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. Two important diagnostic clues in SM are an increased serum tryptase level and the presence of abnormal mast cells in the bone marrow. The current review provides an overview of mastocytosis and its subvariants, the new classification of these diseases, a practical guide for the biological diagnosis and advances and future directions in therapy of these pathologies.     

Quantitative distribution of brush cells in the rat gastrointestinal tract: brush cell population coincides with NaHCO3 secretion

The function of brush cells is obscure, but recent cytochemical studies indicate that rat bile duct brush cells secrete NaHCO₃. The aim of this study was to determine the quantitative distribution of brush cells at 16 sites of the rat gastrointestinal tract and to investigate the role of NaHCO₃ secretion at these sites. Specimens of 16 sites of the gastrointestinal tracts of three female Long-Evans rats were fixed in a periodate-lysine-paraformaldehyde solution. Frozen sections were stained with the anti-cytokeratin 18 antibody, a selective marker for brush cells. The numbers of brush cells were counted from photographs. The percentages of brush cells in the epithelium at the 16 sites were gastric groove, 32.3%; corpus adjacent to the gastric groove, 2.5%; corpus, 0.4%; antrum, 0.4%; duodenum adjacent to the pyloric ring, 2.3%; proximal duodenum, 0%; duodenum facing the bile duct orifice, 0%; distal duodenum, 0.2%; proximal jejunum, 0.1%; transitional site between the jejunum and the ileum, 0.1%; distal ileum, Peyer’s patch dome, 1.5%; and the villi, 0.4%; caecum, 2.1%; proximal colon, 0.2%; middle colon, 0.1%; distal colon, 0.1%; and rectum, 0.1%. We concluded that the population of brush cells is high in the gastric groove, the duodenum adjacent to the pyloric ring, and the caecum, where NaHCO₃ is postulated to neutralize gastric HCL or organic acids produced by enteric bacteria. The brush cell population is low in the duodenum and jejunum, which receive bile and pancreatic juice.     

Cutaneous manifestations in Hymenoptera and Diptera anaphylaxis: relationship with basal serum tryptase

Objectives To compare the clinical presentation of systemic anaphylaxis to Hymenoptera and Diptera with regard to basal serum tryptase (BT) and to evaluate mastocytosis in patients with elevated tryptase.
Patients and Methods The medical records of 140 patients with a history of a systemic reaction to venom were retrospectively reviewed. Symptoms and severity of anaphylaxis and BT were recorded. Most patients with elevated tryptase were screened for mastocytosis: a dermatological examination with a skin biopsy was performed in 19 cases and a bone marrow biopsy in 14 cases.
Results Tryptase was elevated in 23 patients. These patients reported fewer usual skin reactions (urticaria in 26.1% of cases with raised tryptase vs. 76.1% of cases with normal tryptase), more flushing (52.2% vs. 4.3%) and frequently did not present skin reaction (26.1% vs. 9.4%). They presented a more severe reaction (mean grade of severity: 3.48 vs. 2.69). Mastocytosis was diagnosed in seven patients with elevated tryptase: indolent systemic mastocytosis in six cases and cutaneous mastocytosis without systemic involvement in one case. In five cases, mastocytosis was previously undiagnosed. Lesions of cutaneous mastocytosis, diagnosed in five patients, consisted of urticaria pigmentosa in all cases and were often inconspicuous.
Conclusion These results demonstrate particular clinical features of the allergic reaction in patients with elevated BT and the higher frequency of mastocytosis in this population. In patients with a severe anaphylactic reaction without urticaria, but with flushing, tryptase should be assayed and an underlying mastocytosis should be considered.     

Lectin binding patterns of human tissue mast cells indicate marked phenotypical diversity.

Glycoconjugate expression by human tissue mast cells (MCs) from various sources (including lymph nodes with signs of chronic non-specific lymphadenitis, skin lesions of urticaria pigmentosa, and bone marrow infiltrates associated with systemic mastocytosis) was studied histochemically with a broad panel of fluorescein-labelled lectins. Of the 19 lectins applied, 11 (sugar specificities: fucose, N-acetylgalactosamine and neuraminic acid) did not stain any MCs, while 8 (sugar specificities: mannose, N-acetylglucosamine, and galactose) were found to bind to MCs. These lectins exhibited different binding patterns in various disease entities. Only a few of these 8 lectins (in particular, phythaemagglutinin-L) produced strong staining of the MCs in most or all of the cases. Some (e. g. phythemagglutinin-E) produced only weak staining, and this in only a few cases. The lectins used, however, did not distinguish between reactive and tumorous MCs. Although lectins are therefore unlikely to be of use in resolving problems of differential diagnosis concerning proliferation of MCs, our investigation has shown that tissue MCs exhibit marked phenotypical diversity with regard to their lectin-binding properties.     

Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms

In mast cell (MC) disorders (mastocytosis), clinical symptoms are caused by the release of chemical mediators from MCs, the pathologic infiltration of neoplastic MCs in tissues, or both. Cutaneous mastocytosis is a benign disease in which MC infiltration is confined to the skin. In pediatric cases cutaneous mastocytosis might regress spontaneously. Systemic mastocytosis (SM) is more frequently diagnosed in adults and is a persistent (clonal) disease of bone marrow-derived myelomastocytic progenitors. The somatic c-kit mutation D816V is found in the majority of such patients. The natural clinical course in SM is variable. Whereas most patients remain at the indolent stage for many years, some have aggressive SM (ASM) at diagnosis. Other patients have an associated clonal hematologic non-MC lineage disease (AHNMD). MC leukemia (MCL) is a rare disease variant characterized by circulating MCs and fatal disease progression. The diagnoses of ASM, SM-AHNMD, and MCL might be confused with a variety of endocrinologic, vascular, or immunologic disorders. It is therefore of particular importance to be aware of the possibility of an underlying (malignant) MC disease in patients with unexplained vascular instability, unexplained (anaphylactoid) shock, idiopathic flushing, diarrhea, headache, and other symptoms that might be mediator related. An important diagnostic clue in such cases is an increased serum tryptase level. The current review provides an overview of mastocytosis and its subvariants and a practical guide that might help to delineate mastocytosis from unrelated systemic disorders.     

Anatomical Mapping and Density of Merkel Cells in Skin and Mucosae of the Dog

Merkel cells (MCs) are specialized cutaneous receptor cells involved with tactile sense. Although the distribution of MCs has been extensively studied in humans and rodents, their precise distribution and density throughout skin in the dog has not previously been determined. Knowledge of their distribution could facilitate understanding of their functions. By using of immunohistochemistry, density, and anatomical mapping of the MCs population in the dog skin was determined. Assessment of the MCs innervation was also achieved. Different patterns were noted in epidermis, hair follicles, or mucosa, including variable‐sized clusters, linear or horse‐shaped arrangements, and scattered and individualized cells. MCs revealed great variations in density and distribution over the body surface, with the highest numbers in oral mucosa and facial skin. There was no correlation of MCs density with age, sex, type of breed, coat type or pigmentation. Between 41 and 65% of MCs in hairy and glabrous skin and 8–18% of MCs in oral mucosa were in intimate contact with intraepithelial axon terminals. These findings indicate that canine MCs are numerous in sensory receptive areas and may be associated with the tactile sense in the dog. The present article enhances the knowledge of the skin structure in this species. Anat Rec, 299:1157–1164, 2016. © 2016 Wiley Periodicals, Inc.     

Merkel cell differentiation in trichoblastoma

 Four cases of trichoblastoma rich in Merkel cells (MCs) are reported. They occurred in two men and two women, with ages ranging from 58 to 76 years (mean 67.5 years). MCs were detected immunohistochemically with antibodies to keratin 20, chromogranin A and neuron-specific enolase (NSE). In an attempt at better definition of the nature and role of MCs in trichoblastoma, the distribution of MCs in normal adult and fetal skins obtained at autopsy was studied. In addition, ten cases of sebaceous naevus of Jadassohn (NSJ) were evaluated along similar lines. MCs made up 2–20% of the tumour cells in trichoblastomas; they were present in normal fetal skin and were rare in normal adult skin. All but one of the cases of NSJ showed numerous positive cells in the epidermal component of the lesion with all three antibodies. Six basal cell carcinomas and one syringocystadenoma papilliferum associated with NSJ were negative with keratin 20, chromogranin A and NSE antibodies, whereas a minute trichoblastoma arising against the same background was positive for these markers. Hair follicle cell tumours may recapitulate the skin embryogenesis, as numerous MCs are present in fetal follicles, but only occasional such cells are seen in adult skin. Received: 26 February 1998 / Accepted: 22 April 1998     

小腿内侧神经血管复合体岛状皮瓣的应用解剖

目的 :为小腿内侧神经血管复合体岛状皮瓣的设计提供解剖学基础。方法 :在 5 4侧下肢标本上解剖观察了大隐静脉及隐神经营养血管的来源、走行、分支、分布及吻合情况。结果 :小腿内侧浅筋膜层营养血管链由隐动脉、胫后动脉肌间隔皮支及内踝前动脉构成 ,沿大隐静脉及隐神经分布 ,三者密切相关 ,构成一复合体。血管链筋膜皮支分布达外侧 5 .2cm ,内侧 4.0cm。结论 :以小腿内侧神经血管复合体为蒂截取岛状皮瓣可用于膝周、足背及足跟软组织缺损的修复。     

Myoepithelial cells in salivary gland tumors. An immunohistochemical study

Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.     

Characterization of cellular dermal infiltrates in human cutaneous mastocytosis

Biopsies of lesional and nonlesional skin from 14 patients with localized cutaneous or associated systemic mastocytosis were examined by ultrastructural and immunohistochemical techniques. Mast cells within lesions of the dermis were highly variable between patients with regard to cell number and extent of degranulation, although lesional sites consistently contained more mast cells than did nonlesional sites. Two mast cell patterns were identified based upon granule morphology. In biopsies from 8 patients, the majority of granules contained electron-dense amorphous zones; crystalline lattices; and indistinct, incomplete solid scrolls forming parallel lamellae. In biopsies from 6 patients, in addition to these granules, there were also granules composed of electron-dense amorphous zones, reticulated matrices, and/or distinct scrolls with lucent cores interrupted by dense spheres. The granule morphology for the first group (N = 8) was identical with that seen in the preponderant type of skin mast cell of 6 normal control subjects, whereas the granule morphology of the second group (N = 6) displayed an abnormal ultrastructural phenotype for skin that included granule types normally found not only in skin but also in intestinal lamina propria and lung. For individual patients, the patterns of granule ultrastructure were consistent between clinically nonlesional and lesional skin. A minority of cells in both patient groups appeared primitive ultrastructurally, exhibiting rudimentary, Golgi-associated progranules; monocyte-like morphologic characteristics; and mitotic activity. Moreover, when mast cells in lesional skin were screened for a limited panel of surface antigens, they displayed common patterns of reactivity (M718+, HLA-DR/DQ+, CD4+), and in a selected case, immunoelectron microscopy confirmed the presence of these antigens on mast cell plasma membranes. Dermal mast cells from normal donors (N = 6) lack these epitopes. These observations suggest that infiltrates in cutaneous mastocytosis may exhibit phenotypic characteristics not only of cutaneous mast cells, but in some patients also of mucosal mast cells. In either circumstance, the mast cells may display antigenic determinants common to monocyte/macrophages. Concordance of granule phenotype between lesional and clinically uninvolved skin of individual patients furthers the notion that even localized mastocytosis reflects covertly defective systemic mast cell homeostasis.     

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.     

Mastocytosis and allergy

PURPOSE OF REVIEW: To illustrate features of allergy in mastocytosis. RECENT FINDINGS: The rates of atopy in patients with mastocytosis have generally been found to be similar to those of the normal population, although the incidence of anaphylaxis is much higher in mastocytosis. Introduction of objective pathologic criteria by the WHO for the diagnosis of mastocytosis has greatly facilitated the workup of patients with suspected mastocytosis, and has led to identification of mast cell disease in a subset of patients with anaphylaxis. There is increasing evidence that an activating c-kit mutation (D816V) exists in a subset of patients with recurrent mast cell activation symptoms who have normal-appearing bone marrow biopsies in routine evaluations without skin lesions. The genetic deficiency of alpha tryptase has not been found to influence serum tryptase levels in patients with mastocytosis. SUMMARY: Pathologic mast cell activation is a key finding in both allergic diseases and mastocytosis, albeit caused by entirely different mechanisms. Mastocytosis should be suspected in patients with recurrent anaphylaxis, who present with syncopal or near-syncopal episodes without associated hives or angioedema.     

Mast cells and eosinophils in feline allergic dermatitis: a qualitative and quantitative analysis

Mast cells (MCs) and eosinophils are prominent in the perivascular infiltrate of cats with allergic dermatitis. In the skin of allergic cats MCs were mainly observed diffusely in the superficial dermis, while eosinophils were found mainly in the deep dermis in a perivascular pattern. MC counts were significantly higher in cats with allergic dermatitis (P < 0.05) than in healthy control cats, but the number varied widely. Moreover, the numbers of eosinophils in the skin of allergic and control cats differed significantly (P < 0.05) none being found in the latter. There was no significant correlation between numbers of mast cells and eosinophils in the same biopsy sample. In the allergic cats, a significantly lower number of MCs was detected by staining for tryptase than by staining for chymase or by Astra blue staining. Additionally, the chymase: tryptase ratio in healthy cats was reversed in cats with allergic dermatitis. These changes were observed in lesional and nonlesional skin of cats with allergic dermatitis. The findings indicate a generalized effect on MCs in allergic dermatitis. In addition, eosinophils are an important indicator of allergic dermatitis.     

Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor

We previously reported that subcutaneous (s.c.) administration of stem cell factor (SCF), the ligand for the c-Kit receptor, to the back skin of mice promotes marked local increases in the numbers of cutaneous mast cells (MCs), and that cessation of SCF treatment results in the rapid reduction of cutaneous MC populations by apoptosis. In the present study, we used the 125I-fibrin deposition assay, a very sensitive method for quantifying increased vascular permeability, to assess whether the clearance of large numbers of apoptotic MCs is associated with significant cutaneous inflammation. The s.c. injection of rrSCF164 (30 or 100 microg/kg/day) or rrSCF164-peg (polyethylene glycol-treated SCF, 30 or 100 microg/kg/day) for 23 days increased the numbers of dermal MCs at skin injection sites from 5.1+/-0.7 MCs/mm2 to 36.4+/-4.1, 34.7+/-9.7, 52.5+/-5.8, and 545+/-97 MCs/mm2, respectively. In contrast, MC numbers were markedly lower in mice that had been treated with SCF for 21 days, followed by 2 days of injection with the vehicle alone. Notably, when tested during the period of rapid reduction of skin MCs,125I-fibrin deposition in the skin was very similar to that in mice receiving continuous treatment with SCF or vehicle. We conclude that the rapid elimination of even very large populations of MCs by apoptosis, which also results in the clearance of the considerable quantities of proinflammatory products stored by these cells, does not lead to significant local cutaneous inflammatory responses.     

Increased fibronectin production by cell lines from hypertrophic scar and keloid

Primary cell lines of fibroblasts from 8 tissues were established--three from hypertrophic scars (HS), one keloid (K) and four from the normal uninvolved dermis adjacent to each lesion. The objective was to quantify and compare all eight cell lines on the basis of fibronectin (FN) produced per cell and per total protein (PR). Two hypertrophic scars and their adjacent skin cell lines were evaluated by the ELISA method for FN and a micro Lowry assay for PR. The scar lines showed statistically significant increases in the amount of FN/cell compared to the cell lines from their adjacent normal dermis. The third hypertrophic scar and the keloid with their adjacent skin cell lines were assayed for FN and PR by radioimmunoprecipitation. Subconfluent cells were metabolically labeled with 35S-methionine for 20 hours. Harvested media and cell monolayers were assayed for radioactivity incorporated into FN and PR. The percentage of FN/PR was significantly higher in media for HS and K compared to the adjacent normal skin lines in the three passages tested. These results support our previous immunofluorescence studies and demonstrate that a fibroblast-type cell line from a hypertrophic scar or keloid produces more FN/PR over time than the normal fibroblast-type cell line from adjacent uninvolved dermis.     

Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients

BACKGROUND: Systemic mastocytosis (SM) is a condition typically characterized by an increased number of mast cells in the bone marrow or in skin areas known as urticaria pigmentosa. Patients may present with flushing, itching, gastrointestinal symptoms, arrhythmias, headaches and osteoporosis. Some patients experience systemic symptoms indicative of SM in the absence of a positive bone marrow or skin biopsy, and are known as 'clinical mastocytosis', but are herein referred to as suspected of having systemic mastocytosis. Serum tryptase has been increasingly used as a biochemical marker of mastocytosis, but is not always elevated. OBJECTIVE: To investigate the association of serum levels of two key mast cell mediators, interleukin-6 (IL-6) and tryptase, to each other and with disease severity in patients with mastocytosis. METHODS: Patients responded to an announcement from the Systemic Mastocytosis Society (USA) and submitted frozen serum samples, but the precise diagnosis made by their own health providers was not known until after the assays were completed. There were 9 suspected systemic mastocytosis (SuSM), 3 cutaneous mastocytosis (CM), 11 indolent systemic mastocytosis (ISM), and 3 aggressive systemic mastocytosis (ASM). Five normal volunteers (3 females/2 males) also submitted samples, as did 33 cardiac patients without coronary artery disease. For 2 days prior to and during the collection period, mastocytosis patients were asked to abstain from any over-the-counter or food products containing biogenic amines, as well as drugs prescribed for this condition. Serum levels of IL-6 and tryptase were measured using established assays. RESULTS: Twenty-six patients (14 females/12 males) submitted serum samples. There were 9 cases of SuSM (6 females/3 males) in whom tryptase values were borderline normal; IL-6 values were slightly elevated with one being high. In 3 cases of CM (2 females/1 male), both tryptase and IL-6 were slightly elevated. In patients with ISM (5 females/6 males), only 6/11 had any tryptase elevated significantly as compared to 9/11 with elevated serum IL-6. Three patients with ASM had significant elevations of both IL-6 and tryptase. The most consistent finding was that of IL-6 elevations in 7/7 patients (3 females/4 males) who reported symptoms of osteoporosis and/or bone pain (1 SuSM, 3 ISM, 3 ASM) in the absence of any coexisting condition involving bone pathology. CONCLUSION: Serum IL-6 is elevated in mastocytosis patients and correlates with severity of symptoms and the presence of osteoporosis. High serum IL-6 may not only signify disease progression, but may also participate in the pathophysiology of mastocytosis.     

Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and bcl-x(L)

In an attempt to identify novel diagnostic markers for mast cell (MC)-proliferative disorders, serial bone marrow (bm) sections of 22 patients with mastocytosis (systemic indolent mastocytosis, n = 19; mast cell leukemia [MCL], n = 1; isolated bm mastocytosis, n = 2) were analyzed by immunohistochemistry using antibodies against CD2, CD15, CD29, CD30, CD31, CD34, CD45, CD51, CD56, CD68R, CD117, HLA-DR, bcl-2, bcl-x(L), myeloperoxidase (MPO), and tryptase. Staining results revealed expression of bcl-x(L), CD68R, and tryptase in neoplastic MCs (focal dense infiltrates) in all patients. Mastocytosis infiltrates were also immunoreactive for CD45, CD117 (Kit), and HLA-DR. In most cases, the CD2 antibody produced reactivity with bm MCs in mastocytosis, whereas in control cases (reactive bm, immunocytoma, myelodysplastic syndrome), MCs were consistently CD2 negative. Expression of bcl-2 was detectable in a subset of MCs in the patient with MCL, whereas no reactivity was seen in patients with SIM or bm mastocytosis. Mastocytosis infiltrates did not react with antibodies against CD15, CD30, CD31, CD34, or MPO. In summary, our data confirm the diagnostic value of staining for tryptase, Kit, and CD68R in mastocytosis. Apart from these, CD2 may be a novel useful marker because MCs in mastocytosis frequently express this antigen, whereas MCs in other pathologic conditions are CD2 negative.     

A portable reflectometer for the rapid quantification of cutaneous haemoglobin and melanin

A portable reflectance instrument for the rapid quantification of cutaneous haemoglobin and melanin is presented. Light emitting diodes (LEDS) are used to illuminate the skin and a silicon photodiode to detect the light diffusely reflected from the surface. Reflectance measurements are made at only three wavelengths and the problems of pigment quantification consequent upon this are discussed. In addition to quantification of haemoglobin and melanin, qualitative information on the redox state of the blood may also be obtained. Measurements made on a port wine stain, which had been treated with 576 nm CW laser radiation at times between 1 and 6 months previously, provided information on the vascular response to this thermal injury. Despite the treated area visually appearing normal at 6 months post-treatment the measured levels of deoxygenated and total haemoglobin were still markedly higher than those in the adjacent uninvolved skin. The cutaneous pigment indices are insensitive to skin movement and almost all body sites are suitable for measurement.