Microabscess Formation Research Articles

Right Lower Quadrant Pain in a Patient With Inflammatory Bowel Disease of Undetermined Type

A 48-year-old man diagnosed with inflammatory bowel disease of undetermined type 6 years earlier presented with sharp nonradiating right lower quadrant pain. He denied fever, chills, nausea, vomiting, diarrhea, or anorexia. The patient had been in clinical remission on azathioprine and mesalamine. Physical examination was significant for right lower quadrant tenderness without rebound or guarding. His white blood cell count and hemoglobin were normal. A computed tomography scan demonstrated cecal inflammation with associated 5-cm phlegmon (Figure A, arrow). The appendix was not visualized. The terminal ileum appeared narrowed at the ileocecal valve. The patient was treated with antibiotics and bowel rest. Colonoscopy revealed a 4-cm nonobstructing mass in the cecum (Figure B). The remainder of the colon was normal without mucosal breaks or friability. Biopsies of the mass revealed normal colonic mucosa with mild inflammation and mild architectural change. Figure The patient underwent diagnostic laparoscopy revealing an abnormal enlarged appendix. Laparoscopic appendectomy was performed. The surgical specimen measured 5.6 × 4.5 × 3.0 cm and contained no masses. Histologic examination (Figure C; hematoxylin and eosin, bar = 200 μm; Courtesy of W. Sandy Twadell, MD) demonstrated transmural acute and chronic inflammatory infiltrates. Crypt destruction with microabscess formation (arrowhead) and architectural distortion in the form of crypt branching (small arrow) were present, as were poorly formed granulomas with focal giant cells (large arrows). The findings favored a diagnosis of Crohn's disease (CD), changing our patient's diagnosis to Crohn's colitis with appendiceal involvement. Data from our patient's initial diagnosis were reviewed. Colonoscopy revealed patchy colitis with moderate to severe ulceration. The terminal ileum was not intubated, although small bowel follow through revealed a normal fold pattern in the terminal ileum. Random biopsies demonstrated active colitis and areas of acutely inflamed granulation tissue without granulomas or chronic changes. Colonoscopy performed 1 year after diagnosis demonstrated pseudopolyps from the ascending to sigmoid colon and few erosions from the transverse to sigmoid colon. Biopsies revealed chronic active colitis without granulomas. Granulomatous involvement of the appendix is rare and is found in 0.1%–2% of all appendectomy specimens.1 Involvement of the appendix in patients with CD is as high as 40%2; however, symptomatic appendicitis caused by appendiceal CD is uncommon. Our patient developed appendicitis in the setting of mucosal healing of the colon while on immunosuppressive therapy. The reasons for this are unclear and speculative, but may be caused by persistent inflammation in the submucosa, mucosa, and/or serosa of the appendix resulting in luminal obstruction and appendicitis. It is also possible that lymphoid cells within the appendix served as a focal point for recurrent CD. Finally, we cannot exclude the possibility that our patient coincidentally developed “classic” appendicitis superimposed on histologic CD. Symptoms of granulomatous disease of the appendix are similar to acute appendicitis and include fever, right lower quadrant pain, nausea, and anorexia. Other causes of appendiceal granulomatous disease include infection (eg, Yersinia, Mycobacterium tuberculosis, Campylobacter), foreign body reaction, appendiceal or cecal diverticulitis, chronic beryllium poisoning, and sarcoidosis. Our patient did well postoperatively. Azathioprine and mesalamine were continued. He will begin surveillance colonoscopies next year.

Tricuspid valve endocarditis complicated by septic pulmonary embolism in an intravenous drug user

Case reportA 32-year-old woman collapsed suddenly in the early hoursof the morning after visiting the toilet. Her partner made anemergency call immediately and started telephone-assistedcardiopulmonary resuscitation. Subsequent professionalresuscitation efforts were unsuccessful, and the woman waspronounced dead at the scene. She was known to be a long-term intravenous drug (IVD) user. A medicolegal autopsywas requested considering the woman’s young age and herspecific history of IVD abuse.Autopsy revealed the body of a poorly nourished Cau-casian woman, 162 cm in height and 55 kg in weight. Onexternal examination, there were prominent areas ofdepigmentation of the skin in the bilateral groin area, theanterior part of the right thigh, and the left cubital fossa.Fresh subcutaneous hemorrhages were seen on the anteriorpart of the right thigh with fresh puncture marks. Externalexamination also revealed multiple petechial hemorrhageson the right lower leg. Other external findings wereunremarkable.Dissection of the heart (weight, 280 g; dimensions13 9 10 9 4 cm) showed almost complete destruction ofthe anterior and septal cusps of the tricuspid valve (Fig. 1).The edges of the ulcerated cusps contained yellowishgranular vegetations. A smaller shaggy vegetation was alsopresent on the atrial aspect of the posterior cusp of thetricuspid valve, but the degree of destruction of the pos-terior cusp was not as severe as that of the anterior andseptal cusps. The leaflets of the tricuspid valve wereedematous and slightly coarse. A yellowish mass with aslightly granular surface was wedged into both branches ofthe pulmonary artery, causing complete obstruction(Fig. 2). The cardiac muscle was grossly normal. Therewas no septal defect. No pathological change was seen inthe coronary arteries.Further findings included septic changes of the spleen(weight, 460 g), congestion of the internal organs, and lungand brain edema.Histological examination of the lesions on the tricuspidvalve and the mass from the pulmonary artery revealed anorganizing thrombus with numerous colonies of bacteria,focal areas of acute inflammation, and microabscess forma-tion (Fig. 3a). Gram staining displayed gram-positive coc-cobacilli (Staphylococcus aureus). Histological examinationof the heart showed dispersed occlusions of small intramyo-cardial arteries bythrombicontaininglarge numbersofgram-positive bacteria with acute inflammation of adjacent areas ofmyocardium (Fig. 3b). There were no signs of nuclear atypiain the cardiomyocytes. Focal microabscesses containinggram-positive bacteria, karyorrhectic debris, and polymor-phonuclear cells surrounded small vessels in both lungs(Fig. 3c). Histologically proven focal and segmental septicglomerular infarcts were present in both kidneys (Fig. 3d).

Histological changes after treatment for localized fat deposits with phosphatidylcholine and sodium deoxycholate

Phosphatidylcholine (PPC) and sodium deoxycholate (DC) injections have been used cosmetically to reduce localized fat, but to date, few studies have addressed the histological effect of human fat tissue following injections of PPC and DC. We injected PPC and DC mixed with normal saline into the patient's abdominal area. Examinations of postinjection tissue revealed marked changes within the subcutaneous fat. We observed important microscopic evidence of substitution of fat by fibrosis, marked inflammatory infiltration with microabscess formation in the dermis, and septal and lobular panniculitis with thick fibrous septa. Fat necrosis with microcalcification and cyst formation were observed in the subcutaneous fat. Fibroid necrosis with extravasation was noted in the small vessels around fat necrosis. Therefore, careful use of PPC and DC is recommended when patients want to cosmetically reduce localized fat.

IL-1R1 Signaling Facilitates Munro’s Microabscess Formation in Psoriasiform Imiquimod-Induced Skin Inflammation

Munro’s microabscesses contain polymorphonuclear leukocytes and form specifically in the epidermis of psoriasis patients. The mechanism whereby the neutrophils are recruited into the epidermis is poorly understood. Using a combination of human and mouse primary keratinocyte cell cultures and the imiquimod-induced psoriasis-like mouse model of skin inflammation we explored the role of interleukin-1 (IL-1) signaling in microabscess formation. In vitro imiquimod stimulated production of IL-1α and neutrophil recruiting chemokines. Imiquimod activated chemokine expression was dependent upon adenosine signaling and independent of IL-1α and IL-1 receptor type 1 (IL-1R1); nevertheless, IL-1α could enhance chemokine expression initiated by imiquimod. Topical application of imiquimod in vivo led to epidermal microabscess formation, acanthosis and increased IL-1α and chemokine expression in the skin of wild type mice. However, in IL-1R1 deficient mice these responses were either absent or dramatically reduced. These results demonstrate that IL-1α and IL-1R1 signaling is essential for microabscess formation, neutrophil recruiting chemokine expression and acanthosis in psoriasis-like skin inflammation induced by imiquimod.

CD8+ T Cells Mediate RAS-Induced Psoriasis-Like Skin Inflammation through IFN-γ

The RAS signaling pathway is constitutively activated in psoriatic keratinocytes. We expressed activated H-RASV12G in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses and increased Th1/Th17 and Tc1/Tc17 skin infiltration. The majority of skin infiltrating CD8+ T cells co-expressed IFN-γ and IL-17A. When RAS was expressed on a Rag1−/− background, microabscess formation, iNOS expression and keratinocyte hyperproliferation were suppressed. Depletion of CD8+ but not CD4+ T cells reduced cutaneous and systemic inflammation, the RAS-induced increase in cutaneous Th17 and IL-17+ γΔ T cells, and epidermal hyperproliferation to levels similar to a Rag1−/− background. Reconstitution of Rag1−/− inducible RAS mice with purified CD8+ T cells restored microabscess formation and epidermal hyperproliferation. Neutralization of IFN-γ but not IL-17A in CD8+ T cell reconstituted Rag1−/− mice expressing RAS blocked CD8-mediated skin inflammation, iNOS expression and keratinocyte hyperproliferation. These results show for that CD8+ T cells can orchestrate skin inflammation with psoriasis-like pathology in response to constitutive RAS activation in keratinocytes, and this is primarily mediated through IFN-γ.

Biliary Obstruction After Short-Time Choledochal Clamping in Rats

IntroductionBiliary complications after liver procedures can lead to morbidity and poor survival. AimThe aim of this study was to evaluate the hepatic function after quick clamping of the common bile duct (BD) in Wistar rats. MethodsTwelve male Wistar rats with a mean weight of 323.14 g were anesthetized with sodium thiopental intravenous (IV). The common BD Clamping Group (BDCG; n = 6) was submitted to an abdominal incision (2 cm); the BD was isolated, dissected, and underwent clamping for 10 minutes with a microvascular clamp. After this time, the clamp was removed and the incision closed. The Sham Operation Group (SOG; n = 6 rats), under normal conditions, were subjected only to anesthesia and laparotomy and later control tests. On the 28th day liver and choledoch biopsy and biochemical tests were performed on all animals: total bilirubin (TB), alkaline phosphatase (ALK-P), aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and gamma-glutamyl transferase (GGT). After the tests all the rats were humanely killed while still under anesthesia. ResultsIn this study 83% of the animals in the BDCG had large dilatation of the common BD with ductular proliferation, formation of septae, as well as multiple foci of parenchymal necrosis including micro-abscess formation. We also observed alterations in biochemical tests (P < .05). ConclusionOur study demonstrated that BD clamping even for a short time was sufficient to generate important morphological alterations in the liver and BD, as confirmed by enzymatic and histological analysis. Therefore, this technique can be used as a model of biliary obstruction for future studies.

Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis

ObjectiveEosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia.DesignWe developed...

Pityriasis Rotunda

We present a male patient with polycythemia vera (PV) in whom pyoderma gangrenosum (PG) was induced by subcutaneous injections of interferon-α2beta (IFN-α2b).The patient presented with a 6 cm wide necrotic ulcer on the external aspect of his left thigh, which was surrounded by an erythematous and indurated plaque. He also had a simetrical but smaller 2 cm of size ulcer on the external aspect of the right thigh. Histopathological examination showed a massive perivascular and interstitial inflammatory infiltrate. It was vastly composed of neutrophils and secondary formation of interstitial neutrophilic microabscesses was also observed.To our knowledge only two cases of PG secondary to IFN-α2b injections have been reported, none of them in a patient with PV. Physicians should be aware of these IFN-α2b-related local adverse effects as they might become extremely severe. Immediate local discontinuation of drug administration is mandatory. In order to avoid these complications, alternating injection sites is highly advisable.

Eosinophilic gastrointestinal diseases—clinically diverse and histopathologically confounding

Eosinophilic gastrointestinal diseases are a group of chronic diseases characterized by a range of symptoms caused by eosinophilic inflammation of various parts of the gastrointestinal tract. Other causes for eosinophilia need to be ruled out prior to making the diagnosis of EGIDs. The most common form of EGID is eosinophilic esophagitis (EoE), an antigen-driven disease that afflicts children and adults and has been identified across the world. Histological features include dense eosinophilia of the esophageal mucosa, eosinophil degranulation, eosinophil microabscess formation, and other features of epithelial inflammation including basal zone hyperplasia and rete pege elongation. Treatments include dietary exclusions and topical corticosteroids.

Mycobacterium chelonaeinfection: a complication of tattooing

We describe an outbreak of Mycobacterium chelonae infection in four young immunocompetent patients who were tattooed by the same artist. All had been previously tattooed without complication, but following the latest tattooing session, they all developed a very similar papular eruption confined to skin that had been newly coloured light grey. On histological examination of the eruption, granulomatous inflammation with microabscess formation was seen, in association with the tattoo pigment. Skin cultures grown under optimal conditions grew M.chelonae, sensitive to clarithromycin, from one patient. M. chelonae was also cultured from the contents and nozzle of an opened bottle of light-grey ink from the tattoo parlour frequented by the patients. Dermatologists should consider mycobacterial infection in patients who develop inflammatory changes within a new tattoo.

Immune reactivity in psoriatic Munro-Saboureau microabscesses, stratum corneum and blood vessels

Background:A characteristic feature of early active psoriatic lesions is the intraepidermal penetration of neutrophils, with attendant formation of Munro-Saboureau microabscesses. Previous immunofluorescence studies have shown reactivity of in vivo binding of stratum corneum antibodies (SCAs) within the Munro-Saboreau microabscesses in cases of psoriasis.Aims:In our study, we aimed to investigate any correlation between the SCAs and the Munro-Saboureau microabscesses.Materials and Methods:We investigated 50 archival biopsies of psoriasis with Munro-Saboureau microabscesses, and attempted to confirm antibody colocalization within these microabcesses via immunohistochemistry staining. As controls, we utilized 50 skin biopsies from healthy patients undergoing esthetic plastic surgery procedures.Results:Within the Munro-Saboureau microabscesses, the following markers were statistically significantly positive relative to controls: CD1a, CD8, CD23, cyclooxygenase-2, myeloid histoid antigen, albumin, fibrinogen, kappa, lambda, von Willebrand factor, IgG, IgM, IgD, complement/C3c, C3d, myeloperoxidase, and carcinoembryonic antigen (P < 0.05). Autoreactivity to blood vessels was also detected, with multiple immunoglobulins and complement factors.Conclusions:We document important correlations between the Munro-Saboureau microabscesses, SCAs, and other immunoreactants.

Immune System Modeling and Related Pathologies

Immune System Modeling and Related Pathologies

Computational Modeling of Microabscess Formation

Bacterial infections can be of two types: acute or chronic. The chronic bacterial infections are characterized by being a large bacterial infection and/or an infection where the bacteria grows rapidly. In these cases, the immune response is not capable of completely eliminating the infection which may lead to the formation of a pattern known as microabscess (or abscess). The microabscess is characterized by an area comprising fluids, bacteria, immune cells (mainly neutrophils), and many types of dead cells. This distinct pattern of formation can only be numerically reproduced and studied by models that capture the spatiotemporal dynamics of the human immune system (HIS). In this context, our work aims to develop and implement an initial computational model to study the process of microabscess formation during a bacterial infection.

Abstract 2858: A novel mouse model for cutaneous T-cell lymphoma reveals a role for IL-15 and activity of a new oral HDAC inhibitor

Abstract Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin's lymphoma representing a spectrum of diseases composed of malignant clonal CD4 (+) helper T lymphocytes. The etiology of CTCL remains to be elucidated and no animal models for CTCL are known. We quantified expression of IL-15 in patients with CTCL and demonstrated aberrant overexpression of IL-15 compared to normal CD4+ T cells (Fold increase = 7.476 ± 1.788 N=3, P=0.0073), that showed direct correlation with the stage of the disease (Fold increase in IL-15 in Stage I patients vs. Stage III patients = 3.283 ± 0.8246 vs. 7.476 ± 1.788, N=3 each, P=0.02). We engineered a transgenic (tg) mouse to constitutively and globally overexpress murine IL-15. These mice develop alopecia and cutaneous lesions in all mice within 6 weeks of birth, characterized by erythematous plaques/patches, erythroderma, pruritis and early death compared to wild type (WT) controls (49 weeks vs. 100 weeks, P=0.0003). Skin lesions showed an infiltration of atypical lymphocyte in the dermis and throughout the epidermis including the formation of classic Pautrier's microabscesses as seen in human CTCL. Immunophenotypic analysis of the skin T-cells from these mice revealed ∼25 fold increase in CD3+ T-cells compared to WT littermates. Intradermal CD4+ cells from CTCL mice were predominantly CD62L- and significantly higher than WT mice (P=0.007). Immunohistochemistry showed high expression of cutaneous lymphocyte antigen (CLA) and CCR4 on skin sections of CTCL mice, consistent with a skin-specific homing pattern as seen in human CTCL. Cells obtained from the skin of these IL-15tg CTCL mice could be successfully engrafted into skin of SCID recipient mice with reproducible histological lesions. Consistent with human studies, CTCL mice exhibited significantly increased levels of Hdac-1 in CD4+ T cells when compared to their WT counterparts (P = 0.0013). To investigate the importance of IL-15 in this process, we cultured sorted mouse WT (CD3+CD4+) T-cells in medium supplemented with 100ng/ml IL-15 and observed a significant increase in Hdac-1 expression at the mRNA and protein level within 10 days of culture, compared to freshly isolated WT CD4+ T cells (N=3 each, p =0.02). In a randomized, placebo-controlled trial of an orally administered novel HDAC inhibitor, AR-42 (Arno Therapeutics, Inc, Parsippany, NJ; Sargeant AM et al, Cancer Research, 2008) to IL-15 tg mice with CTCL, we observed an improvement in skin lesions and a marked reduction in T-cell dermal infiltrate as early as 12 days post-treatment. In conclusion, we provide evidence for a reproducible in vivo mouse model of spontaneous CTCL that appears to mimic the human condition. Further, we provide evidence for a role of aberrant IL-15 expression in the genesis of both human and experimental CTCL, and alterations in Hdac-1 expression that may to serve as an appropriate target for a novel oral HDAC inhibitor now in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2858. doi:10.1158/1538-7445.AM2011-2858

Dermatitis Herpetiformis (DH) in Association with H. pylori Infection: Description of a Case Report

Dermatitis herpetiformis (DH) is an autoimmune blistering disorder associated with a gluten-sensitive enteropathy (GSE), and is generally accepted as a cutaneous manifestation of celiac disease and is characterized by grouped excoriations; erythematous, urticarial plaques; and papules with vesicles. We reported an interesting case of adult DH occurred in a 30 year old Sudanese young adult with chronic inflammatory bowel disease, presented with typical string of pearls in the face, trunk and extremities for 2 months duration. The case is diagnosed and confirmed as DH where histopathologically shows a sub-epidermal bulla with microabscess formation, sigmoidoscopy and H. pylori ELISA test were positive IgA. Our case had an adult onset of presentation. Clinical features and histopathology are typical. It is associated of H. Pylori, although poorly responding to triple therapy (Doxycyclin 100 mg bid for 8 days, Cefixime 400 mg for 5 days and Rabeprazole as proton pump inhibitor (PPI) 20 mg for 28 days), but focusing as possible antigen was of paramount concern as possible causative antigen; as in this case all serological specific tests for Coeliac disease were negative. The case was considered to be the second case of DH with CIBD due to H. Pylori been reported in Sudan.

Nodular lymphangitis: Report of a case with presentation of a diagnostic paradigm

A 54-year-old man with asthma, mitral valve prolapse, and a back injury developed erythematous nodules that progressed along the lymphatic drainage of his right arm. Skin biopsy revealed granulomatous inflammation with microabscess formation. Culture confirmed Mycobacterium marinum infection. The patient was treated with clarithromycin, ethambutol, rifampin, and topical silver sulfadiazine. Oral doxycycline hyclate was later added because of slow healing. Mycobacterium marinum is one of a group of infectious agents that can cause nodular lymphangitis. Sporotrichoid lesions most commonly develop after cutaneous inoculation with Sporothrix schenckii, Leishmania species, Nocardia species, and Mycobacterium marinum. A thorough clinical history and physical examination can narrow the differential diagnosis by eliciting information about the etiologic setting, incubation time, clinical appearance of the lesions, and presence or absence of systemic involvement for each of the causative organisms. Skin biopsy and microbiological tissue cultures are essential for diagnostic confirmation. The differential diagnosis and a suggested diagnostic paradigm will be reviewed.

Experimental candidosis on rat’s tongue

The purpose of this study was to evaluate the development of candidosis in rat’s tongue after intraepithelialinjections of Candida albicans. Fifty rats (Rattus norvegicus, Albinus, Wistar), originally negative for the Candidaspp. received ten intraepithelial injections of C. albicans on the dorsal tongue. Groups of five animals werekilled after 1, 2, 4, 6, 8, and 12 hours and 1, 2, 7, and 15 days after the injection. The rat’s tongues weresurgically removed and then macroscopic and microscopic analyses were performed. The development of candidosislesions was observed in all the rats studied. One hour after the injection, the development of germ tubesfrom the yeast cells could be observed. After 4 hours, Candida spp. pseudohyphae penetrated the epithelial cellswith the formation of microabscesses. After 24 to 48 hours, the epithelial areas with pseudohyphae invasionpresented desquamation, hyperplasia of the basal layer and discrete inflammation of the connective tissue. Afterseven days, few pseudohyphae could be observed. The epithelium presented acanthosis, hyperkeratosis and lossof filiform papillae. After 15 days, neither yeasts nor pseudohyphae were found. In some areas, the epitheliumpresented acanthosis and loss of filiform papillae. It can be concluded that the intraepithelial injection of Candidaalbicans on the dorsal rat tongue caused candidosis lesions in all the animals studied. C. albicans waspresent until seven days after the injections.

Exaggerated IL-23-induced psoriasis-like inflammation in mice lacking CCR4 (135.32)

Abstract Recent evidence strongly implicates the IL-23/Th17/Th22 axis in psoriasis, and intradermal injection of IL-23 produces local psoriasis-like inflammation, which depends on IL-22 and other IL-10-family cytokines. CCR4 is a chemokine receptor thought to be important for T cell trafficking to skin, and is expressed on all Th2 cells, as well as many Th17 cells and Treg. We tested CCR4 deficient mice in the IL-23 injection model and found, surprisingly, that they had an exaggerated inflammatory response, with increased swelling of the injected skin, greater acanthosis, parakeratosis, and microabscess formation, higher numbers of infiltrating neutrophils, T cells and dendritic cells, and higher numbers of pro-inflammatory cytokines, including: IL-17a, IL-17f, IL-19, IL-22 and TNFα. Remarkably, despite the greater inflammation, Foxp3+ cells were not increased in the IL-23-injected skin of the CCR4 deficient mice, producing a higher effector T cell/Treg ratio as compared with wild-type mice. Our results suggest that CCR4 is important, not for effector functions, but for recruiting cells to down-modulate Th17/Th22-mediated inflammation in skin. These findings may help in understanding how inflammation is regulated in psoriasis and related disorders. Supported by the Intramural Research Program, NIH, NIAID.

Epidermal expression of oncogenic ras subverts cytotoxic inflammation by skewing infiltrating myeloid cells towards an immunosuppressive phenotype. (100.16)

Abstract Cancer development is frequently accompanied by inflammation and immune activation. The nature of this inflammatory response, however, is non-uniform and can consist of cells with opposing functions. To characterize the innate immune response to neoplastic epithelial tissue, we used an epidermally-restricted transgenic mouse model of oncogenic H-Ras expression in which epidermal hyperplasia and premalignant progression induces aberrant myelopoesis and cutaneous hyperinflammation associated with the formation of myeloid resident epithelial microabscesses. Antibody mediated depletion of neutrophils concurrent with transgene activation ablated neutrophil infiltration and microabscesses resulting in increased epidermal thickening relative to isotype controls. Neutrophils isolated from mice expressing ras for 1 week killed keratinocytes in vitro, suggesting that the in vivo myeloid response to oncogenic ras expression is initially a cytotoxic one. Simultaneously, there is cutaneous upregulation of genes implicated in the activation, function and recruitment of myeloid derived suppressor cells (MDSC) such as GMCSF, GCSF, MMP9, VEGF, S100A8/9, CCL2, and IL1β. This coincides with upregulation of IL4Rα on myelocytes, increased percentage of Tregs, and decreased effector T cell responses from 1 to 2 weeks post H-Ras expression. These data suggest that the acute cytotoxic neutrophil response is replaced by a suppressor myeloid phenotype that could enhance neoplastic progression.

Granulomatous mastitis: Presentation, treatment and outcome in 43 patients

Background Granulomatous mastitis is a rare benign breast condition commonly affecting women of child-bearing age. It is characterised histopathologically by the presence granuloma and microabscess formation. It is frequently mistaken for inflammatory breast carcinoma both clinically and mammographically. The aim of this study was to retrospectively review the clinical presentation, radiological investigation, histopathological features, treatment and outcome of granulomatous mastitis of women presenting to Ripas Hospital between October 1997 and June 2009. Results Forty-three patients with a mean age of 34 years presented with a diagnosis of granulomatous mastitis. All patients presented with a palpable breast lump; 24 (56%) patients also experienced pain in the lump and 3 (7%) patients also had associated nipple discharge on presentation. The role of radiological imaging is found to be limited in differentiating GM from other inflammatory and malignant conditions of the breast. Forty (93%) patients underwent a surgical procedure as the main treatment; in the form of excision or incision and drainage of the breast lesions. Mean follow-up was 15 (range 1–80) months with recurrence in 10 (23%) patients. Conclusion Granulomatous mastitis presents clinically with a palpable breast lump. The diagnosis is often only made histopathologically after surgical excision or core biopsy. Complete surgical excision or incision and drainage of the lesion are the main treatment modalities. Treatment with corticosteroids and immunosuppression remains controversial and there is tendency for this condition to recur after treatment.