Histoplasmosis Related to Immunosuppression in a Patient with Crohn's Disease: A Diagnostic Challenge.

BACKGROUND Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) alpha with proven efficacy and known safety profile, is currently widely used in the treatment of inflammatory bowel diseases. Increased risk for serious infections and malignant neoplasms secondary to immunosuppression is a major concern during therapy with this medication. Histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum. Disseminated forms of the disease have immunodepression as a major risk factor. CASE REPORT A 39-years-old man had been followed with refractory fistulizing ileocolonic Crohn's disease using combination therapy (infliximab plus azathioprine) and also receiving short courses of steroids. After 2 years of this immunosuppressive therapy, the patient presented with high fever (39.5ºC) for 5 days, associated with profuse sweating, and moderate pain in the left hypochondrium. The patient was hospitalized. Diagnoses of tuberculosis, malignancy, autoimmune diseases, and bacterial and viral infections were rapidly discarded after investigation. Clinical, laboratory, and image signs of liver involvement prompted a guided percutaneous biopsy, which revealed granulomatous hepatitis, with the presence of fungal structures suggestive of Histoplasma capsulatum. Upon treatment with liposomal amphotericin followed by itraconazole, the patient showed an impressively positive clinical response. CONCLUSIONS TNF blockers, particularly when associated with other immunosuppressors, are a serious risk factor for opportunistic infections. This unusual case of disseminated histoplasmosis in a patient with Crohn's disease using infliximab in combination with azathioprine and steroids emphasizes the need for surveillance of this uncommon but potentially lethal complication before starting TNF blockers therapy.

Human Antigen Leucocyte (HLA)-G and HLA-E are differentially expressed in pancreatic disorders.

BACKGROUND: Little information is available regarding the expression of the immunomodulatory Human Leukocyte Antigen (HLA)-G and -E molecules in pancreatic disorders. AIM: To analyze HLA-G and -E expression in specimens of alcoholic chronic pancreatitis (ACP), idiopathic chronic pancreatitis (ICP), type 1 (T1D) and type 2 diabetes (T2D) and in histologically normal pancreas (HNP). METHODS: HLA-G and -E expression (ACP = 30, ICP = 10, T1D = 10, T2D = 30 and HNP = 20) was evaluated by immunohistochemistry in three different areas (acini, islets and inflammatory infiltrate). RESULTS: Acini and islets from HNP specimens exhibited higher HLA-G and -E expression compared to corresponding areas from all other patient groups. In inflammatory infiltrate, HLA-G and -E expression was observed only among the pancreatic disorders. We observed higher HLA-G and -E expression in acini from T2D compared to ACP, as well as higher HLA-G expression compared to ICP. CONCLUSION: The decreased expression of HLA-G and -E in islets and acini together with the expression of these molecules in the inflammatory infiltrating cells were shared features among chronic inflammatory and autoimmune pancreatic disorders evaluated in this study, possibly reflecting tissue damage.

Immunohistochemical expression of p63 in endometrial polyps: evidence that a basal cell immunophenotype is maintained.

OBJECTIVE: Although endometrial polyps likely originate from reserve cells in the basal layer, the underlying biology is not fully understood. One protein that plays an important role in regulating epithelial proliferation and differentiation is the 63-kd membrane protein (p63), which is also a marker of basal and reserve cells in the female genital tract. Our objective was to determine whether p63 is expressed differently in postmenopausal endometrial polyps than in the adjacent endometrium. DESIGN: In this study, 36 specimens of endometrial polyps and 36 samples of the adjacent endometrium were obtained from postmenopausal women through hysteroscopic surgery performed in a tertiary-care university hospital. Immunohistochemistry was used to evaluate the expression of p63 in all samples. RESULTS: The majority of endometrial polyp samples (94.4%) presented nuclear immunostaining for p63, whereas only 5.6% of adjacent endometrium samples were positive for p63 (P < 0.0001). Distribution of p63 immunostaining in the endometrial polyp samples was homogeneous. CONCLUSIONS: Our results provide evidence that a basal cell immunophenotype is maintained in the endometrial polyps seen in postmenopausal women, suggesting that p63 plays a role in the pathogenesis of such polyps.

Biochemical analysis of human breast tissues using Fourier-transform Raman spectroscopy.

We employ Fourier-transform Raman spectroscopy to study normal and tumoral human breast tissues, including several subtypes of cancers. We analyzed 194 Raman spectra from breast tissues that were separated into 9 groups according to their corresponding histopathological diagnosis. The assignment of the relevant Raman bands enabled us to connect the several kinds of breast tissues (normal and pathological) to their corresponding biochemical moieties alterations and distinguish among 7 groups: normal breast, fibrocystic condition, duct carcinoma in situ, duct carcinoma in situ with necrosis, infiltrating duct carcinoma not otherwise specified, colloid infiltrating duct carcinoma, and invasive lobular carcinomas. We were able to establish the biochemical basis for each spectrum, relating the observed peaks to specific biomolecules that play a special role in the carcinogenesis process. This work is very useful for the premature optical diagnosis of a broad range of breast pathologies. We noticed that we were not able to differentiate inflammatory and medullary duct carcinomas from infiltrating duct carcinoma not otherwise specified.

Reactivation of Chagas' disease in a patient with non-Hodgkin's lymphoma: gastric, oesophageal and laryngeal involvement.

Changes in the natural course of Trypanosoma cruzi infection have been associated with immunosuppression. We report here a case of the reactivation of Chagas' disease in a patient with non-Hodgkin's lymphoma with gastric, oesophageal and laryngeal involvement. This is the first report describing the involvement of the larynx by T. cruzi.

Phyllodes tumor with osteosarcomatous differentiation: a comparative immunohistochemical study between epithelial and mesenchymal cells.

AIMS AND BACKGROUND: Phyllodes tumor of the breast with osteosarcomatous differentiation is rare and very little is known about its molecular profile. METHODS AND STUDY DESIGN: An immunohistochemical panel with 37 primary antibodies including cytokeratins, mesenchymal markers, key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors was performed on a formalin-fixed paraffin-embedded sample of phyllodes tumor with osteosarcomatous differentiation in a 49-year-old woman. RESULTS: Antiapoptotic stimuli (survivin) predominated in sarcomatous cells. Antiproteolytic stimuli (TIMP-1, TIMP-2 and PAI) were preponderant in all cells, a surprising fact in view of the aggressiveness of the neoplasm. The immunoprofile of the osteoblastic and stromal cells was quite similar, except for c-erbB-3, c-myc, cyclin D1 and p21. Both exhibited positive cells for actin, MyoD1 and GFAP. CONCLUSIONS: Our results suggest that this osteosarcoma may have originated from metaplasia of stromal cells that underwent a malignant change.

Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women.

OBJECTIVE: To detect the presence of estrogen (ER) and progesterone (PR) receptors in endometrial polyps and adjacent endometrium in postmenopausal women. METHODS: Forty-four consecutively enrolled postmenopausal patients were submitted to operative hysteroscopy. These patients had diagnosed benign endometrial polyp. The presence of ER and PR was determined in endometrial samples and polyps by immunohistochemical method and the slides were evaluated using a semiquantitative analysis. RESULTS: In the glandular epithelium, the median of the ER score was 7.0 in the polyps and 5.0 in the endometrium (P<0.0001) and the median of the PR was 6.0 in the polyps and 4.0 in the endometrium (P<0.0001). In the stroma, the median of the ER score was 6.0 in the polyps and 5.0 in the endometrium (P=0.021) and the median of the PR score was 4.0 in the polyps and 4.5 in the endometrium (P=0.34 ). CONCLUSIONS: Our data suggests that steroids receptors present a crucial role in the phisiopathology of the endometrial polyps in postmenopausal women, specially the estrogen receptors.

EVALUATION OF TERMINAL VERTEBRAL PLATE ON CERVICAL SPINE AT DIFFERENT AGE GROUPS AND ITS CORRELATION WITH INTERVERTEBRAL DISC THICKNESS.

UNLABELLED: To evaluate, by means of histomorphometry, terminal vertebral plate thickness, intervertebral disc thickness and its correlation on different age groups, seeking to identify its correlation. METHODS: C4-C5 and C5-C6 cervical segments removed from human cadavers of both genders were assessed and divided into five groups of 10-year age intervals, from 21 years old. TVP and intervertebral disc thickness evaluation was made by means of histomorphometry of histological slides stained with hematoxylin and eosyn. Lower C4 TVP, upper C5 TVP, and upper C6 TVP de were compared between each other and to the interposed intervertebral disc thickness between relevant TVP. RESULTS: The thickness of terminal vertebral plates adjacent to the same ID did not show statistic differences. However, the comparison of upper and lower vertebral plates thickness on the same cervical vertebra (C5), showed statistical difference on all age groups studied. We found a statistical correlation coefficient above 80% between terminal vertebral plate and adjacent intervertebral disc, with a proportional thickness reduction of both structures on the different cervical levels studied, and also on the different age groups assessed. CONCLUSION: Terminal vertebral plate shows a morphologic correlation with the intervertebral disc next to it, and does not show correlation with the terminal vertebral plate on the same vertebra.