Does a Subset of Localized Chronic Fibrosing Vasculitis Represent Cutaneous Manifestation of IgG4-Related Disease/a Histologic Pattern of IgG4-Related Skin Disease? A Reappraisal of an Enigmatic Pathologic Entity.

Localized chronic fibrosing vasculitis (LCFV) is a rare cutaneous fibroinflammatory and vasculitic process of poorly defined etiology. Furthermore, controversy remains as to whether LCFV represents a primary pathologic process or a histologic pattern. The current case documents a 52-year-old male patient with a scrotal mass and clinical history of a retroperitoneal mass as well as a previously resected tumor of the right submandibular salivary gland displaying morphologic features of eosinophilic angiocentric fibrosis. Histologic examination of the resected scrotal mass revealed a tumefactive lesion characterized by focally storiform fibrosis, obliterative phlebitis, tissue infiltration by IgG4-positive plasma cells, and leukocytoclastic vasculitis. Apart from the leukocytoclastic vasculitis, the scrotal lesion demonstrated characteristic morphologic features of an IgG4-related disease (IgG4-RD). In recognition of the combined histologic findings of both LCFV and IgG4-RD in the scrotal mass, it was postulated that a subset of LCFV cases might represent cutaneous manifestations of IgG4-RD or a new histologic pattern of IgG4-related skin disease (IgG4-RSD). The literature analysis of previously reported LCFV cases appeared to lend credence to this hypothesis. Pathologists should be aware of this new histologic pattern of IgG4-RSD as judicious consideration for additional studies might potentially detect an unexpected systemic IgG4-RD in the patient, particularly in cases of LCFV displaying storiform fibrosis associated with plasma cell infiltrate.

Sperm agglutination: Prevalence and contributory factors.

Agglutination is a finding noted in semen analyses (SAs) that often causes confusion as to its significance. While some have attributed agglutination to antisperm antibodies (ASAs), there are other causes as well, such as genital tract infection and ascorbic acid deficiency. Additionally, it is known that patients with ASAs often have risk factors such as a history of scrotal trauma or surgery. Therefore, we sought to determine the prevalence of agglutination in our patient population and correlate it with these risk factors, regardless of the presence/absence of ASAs. A retrospective study was conducted on the SAs of men seen at a single academic Reproductive Center. Of the 1,095 SAs identified, 133 (12.1%) patients experienced agglutination (61.7% scant, 21.8% moderate and 16.5% excessive). Of patients who underwent multiple SAs, 24 (12.2%) showed variability. Furthermore, patients who underwent scrotal surgery carried 3.4 times the risk of agglutination (X2 p < 0.01) and 5.5 times the risk of variability (X2 p < 0.01) as compared to those patients without a history significant for scrotal surgery. Agglutination is a relatively common finding in men presenting to a reproductive clinic with little intrapatient variability. Scrotal surgery confers a higher risk of agglutination and variability.

A giant primary sclerosing lipogranuloma of the scrotum.

Sclerosing lipogranuloma is a rare, benign disease that can affect several organs, particularly of genitourinary system in males. The majority of the cases are secondary to exogenous foreign bodies. The masses are composed of granulomatous tissue formed around an either exogenous or endogenous lipomatous substance. We describe a 47-year-old male patient who presented with a growing, painless scrotal mass on physical examination. The mass was in 20 cm diameter and the laboratory findings were in normal limits. Pathologic evaluation confirmed the diagnosis of scrotal sclerosing lipogranuloma. To the best of our knowledge, this is the biggest scrotal sclerosing lipogranuloma case in the literature. We aimed with this presentation to keep in mind this benign lesion and also to assist the algorithmic approach.

Effect of vaccination against gonadotropin-releasing factor (GnRF) with Bopriva® in the prepubertal bull calf.

The aim of this study was to evaluate the effect of immunization against gonadotropin-releasing factor (GnRF) with Bopriva(®) (Pfizer Animal Health, Parkville, Australia) in prepubertal bull calves. For the study, 6 calves were vaccinated at the age of 3 and 6 weeks with 1 mL Bopriva(®), and 6 animals served as matched controls. Concentrations of GnRF antibodies, testosterone and LH were determined in serum samples out to 30 weeks after the first immunization. Body weight and scrotal circumference were measured for 59 weeks. At slaughter, 65 weeks after the first immunization, the quality of epididymal sperm was evaluated. The results showed that vaccination against GnRF influenced (P<0.05) anti-GnRF titer, LH and testosterone concentrations as well as scrotal circumference. Antibody titers significantly (P<0.05) increased after the booster vaccination and reached peak values 2 weeks later. Compared to control animals, inhibition (P<0.05) of the prepubertal LH secretion was observed in vaccinated calves at weeks 10 and 12-14 after the first vaccination. In vaccinated calves testosterone concentrations decreased after the booster injection to values below 0.5 ng/mL serum and remained for at least 22 weeks at this low level. Animals vaccinated with Bopriva(®) showed a delay in testes growth and smaller scrotal circumference. Puberty occurred at the age between 46 and 55 weeks in vaccinated and between 38 and 52 weeks in control animals and body weight gain was similar in both groups. All vaccinated bulls attained spermatogenic capacity at slaughter when they were 68 weeks old.

Rosmarinus officinalis L. essential oil inhibits in vivo and in vitro leukocyte migration.

Rosmarinus officinalis L. (Lamiaceae), popularly known as rosemary, is used for food flavoring and in folk medicine as an antispasmodic, analgesic, antirheumatic, diuretic, and antiepileptic agent. Few studies have shown the anti-inflammatory effects of rosemary essential oil (REO). This study evaluated the effects of REO on leukocyte migration through in vivo leukocyte migration and in vitro chemotaxis assay. REO was analyzed by using gas chromatography-mass spectometry, and the main components identified were camphor (27.59%), 1,8-cineole (15.74%), α-pinene (16.58%), and ß-myrcene (10.02%). In rats, administration of REO reduced the number of leukocytes that rolled, adhered, and migrated to the scrotal chamber after carrageenan injection. All doses of REO tested significantly inhibited leukocyte chemotaxis induced by casein. The effects of REO on leukocyte migration highlight an important mechanism of the anti-inflammatory action of rosemary.

Immunocytochemical localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotum.

The present study revealed in detail the subcellular localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of beta-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.

Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)--a histological comparison in male animals.

A N-terminal modified gonadotrophin releasing hormone (GnRH-I, tetanus toxoid-CHWSYGLRPG-NH2) conjugate was evaluated histologically in a number of male animal species (mice, dogs and sheep). The immunogen has previously been shown to be highly effective in rats, by suppressing both steroidogenesis and spermatogenesis. However, cross-species efficacy of peptide vaccines is known to be highly variable. Therefore, a comparative evaluation of reproductive tissues from animals immunized against this immunogen adsorbed onto an alum-based adjuvant was made. The sheep and dogs were chosen, as use of anti-fertility vaccines in these species is important in farming and veterinary practice. Changes in testicular size were measured during the immunization period and the greatest alteration (attributed to gonadal atrophy) was observed in the rat. Following euthanasia, the testicular tissue was evaluated for spermatogenesis. The most susceptible species to GnRH-I ablation was the rat, which showed significant (P < 0.0001) arrest in spermatogenesis compared with untreated controls. Testicular sections taken from treated animals were completely devoid of spermatozoa or spermatids, in comparison with 94% of the untreated controls showing evidence of spermatogenesis. The immunized mice and rams also showed significant arrest (P < 0.0001). There was a 30-45% decrease in spermatogenesis and total azoospermia was not apparent. However, the least responsive were the dogs, which showed little significant variation compared to untreated animals and only a 5% decrease in activity. A comparison of the specific IgG response to GnRH-I indicated that in sheep and dogs the response was not maintained, unlike in rodents, suggesting that suppression of fertility may be due to differences in immune responses in different animal species.

Median raphe cyst in the scrotum, mimicking a serous borderline tumor, associated with cryptorchidism after orchiopecxy.

Median raphe cyst (MRC) is a benign lesion occurring predominantly in the ventral surface of the penises of young men and is an embryological developmental anomaly of the male genitalia. Serous borderline tumors (SBT) are found most frequently in the female ovary and only several cases with SBT of the male genitalia have been reported. We describe a case of MRC with features of SBT, which appeared in the scrotum of a 9-year-old boy after orchiopexy and was associated with surgery for cryptorchidism. The cyst arose on the right testicular tunica and consisted of cystic components with intracystic papillae lined by stratified epithelial cells, some of which showed mild cytological atypia and sporadic mitosis. These epithelial cells expressed CA 125, CA 19-9, carcinoembryonic antigen, estrogen receptor and progesterone receptor. Although no cases of MRC with characteristics of SBT in association with the rete testis has been described, the current report gives additional information for follow-up of cryptorchidism.

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection.

BACKGROUND: Cutaneous manifestations of B-cell chronic lymphocytic leukemia (B-CLL) comprise a wide spectrum of clinicopathologic presentations. In some cases, onset of skin lesions is triggered by antigenic stimulation, and specific skin infiltrates at sites of previous herpes simplex or herpes zoster infection have been well documented. Specific skin manifestations of B-CLL can also be observed at sites typical for lymphadenosis benigna cutis (nipple, scrotum, earlobe), a Borrelia burgdorferi-associated cutaneous B-cell pseudolymphoma. METHODS: We studied specific skin manifestations of B-CLL arising at sites typical for B. burgdorferi-induced lymphadenosis benigna cutis, analyzing tissues for presence of B. burgdorferi DNA using the polymerase chain reaction (PCR) technique. Six patients with B-CLL (M : F = 4 : 2; mean age: 67.8) presented with specific skin lesions located on the nipple (four cases) and scrotum (two cases). RESULTS: Clinically there were solitary erythematous plaques or nodules. Histology revealed in all cases a dense, monomorphous infiltrate of small lymphocytes showing an aberrant CD20+/CD43+ phenotype. In all cases monoclonality was demonstrated by PCR analysis of the JH gene rearrangement. PCR analysis showed in four of the six cases the presence of DNA sequences specific for B.burgdorferi. CONCLUSIONS: Our study demonstrates that infection with B. burgdorferi can trigger the development of specific cutaneous infiltrates in patients with B-CLL.

Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic inflammation.

We investigated morphological alterations induced by s.c. injection of 2.5 microg of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres was observed 1 min after the venom injection, particularly at regions near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions. At this time, damaged endothelial cells were not observed. In rats envenomed as above, but immediately after cardiorespiratory failure induced by deep ether anaesthesia, alterations in the connective tissue structures, as previously described, were not observed. The mediation of this haemorrhage was investigated by injecting the venom into the foot pad of mice and compared to the mediation of oedema. Local haemorrhage was significantly reduced in mice pre-treated with capsaicin or guanethidine or submitted to a surgical section of sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oedema significantly reduced. Indomethacin or dexamethasone pre-treatments significantly reduced the oedema, but not the haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage induced by Bothrops jararaca venom is partially controlled by serotonin and neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema are mediated by different pharmacological systems.