Adult self-healing papular mucinosis on genital skin.

We report a unique case of papular mucinosis on genital skin. The lesion was initially misdiagnosed and mistreated as molluscum contagiosum. The histological sections showed a large amount of mucin with sparse plump fibroblasts. The papules resolved in a few weeks, indicating a very rare form of the adult variant of self-healing papular mucinosis. Genital localization of this peculiar mucinosis, which we suspect may be more common than reported, is an important clinical simulator of sexually transmitted disease, and correct diagnosis is important for appropriate treatment.

Scurvy as cause of purpura in the XXI century: a review on this "ancient" disease.

OBJECTIVE: Scurvy is defined as a deficiency of ascorbic acid, which is an essential exogenous vitamin in humans. Vitamin C is involved in collagen synthesis and its deficit can cause disorders of connective tissue. The most frequent symptoms are weakness, arthralgias, anorexia and depression, commonly associated with follicular hyperkeratosis and perifollicular hemorrhage, with purpura. PATIENTS AND METHODS: A young woman, with a history of malnutrition, manifested purpura and hematoma of the left lower limb. The laboratory tests didn't detect alterations either in coagulation, the platelet count or in the autoimmunity. The total body TC scan didn't show neoplasia or other suspected lesions. Excluding the most important causes of purpura, in consideration of malnutrition, scurvy was suspected. RESULTS: A skin biopsy confirmed the diagnosis. Accordingly to this finding, a treatment with a daily intravenous infusion of vitamin C was started with consequent improvement of hematoma and purpura. CONCLUSIONS: Scurvy is a re-emerging disease, also in western countries. When purpura appears in young adults, scurvy has to be investigated, especially when a history of malnutrition is present. The treatment with vitamin C infusions should be started as soon as possible in order to prevent any complications.

Lymphoepithelioma-like carcinoma of the skin.

The term lymphoepithelioma-like carcinoma identifies a group of nasopharingeal epithelial tumors characterized by aggregates of malignant undifferentiated cells surrounded by a dense reactive lymphoplasmacellular infiltrate. Primary cutaneous localization is rare, with approximately 30 cases reported in literature. We describe a case of primary lymphoepithelioma-like carcinoma of the skin in a 92-year-old woman. Immunohistochemical examination was positive for cytokeratine (KL1 and EMA) as regards epithelial cells, while the lymphocitic infiltrate was positive for LCA and CD3. In situ hybridization for Epstein Barr virus in tumor cells was negative. Electron microscopy showed rounded and occasionally spindle-shaped poorly-differentiated squamous epithelial cells, and a lymphoid stroma consisting mostly of normal-appearing small lymphocytes. Examination of the nasopharynx did not show any tumoral mass and after a 7 years follow-up the patient is free of local and distant recurrences. This tumor affects people aged over 50 years and is localized to the face, but scalp, shoulder and forearm may be involved. Research of Epstein-Barr virus is always negative in this tumor, unlike nasopharingeal epithelial carcinoma. The differential diagnosis of lymphoepithelioma-like carcinoma of the skin may present some difficulties and includes squamous cell carcinoma. Lymphoepithelioma-like carcinoma of the skin is a malignant neoplasm which tends to relapse locally and has a moderate tendency to metastatize.

Atypical thyroid nodules express both HBME-1 and Galectin-3, two phenotypic markers of papillary thyroid carcinoma.

Ninety-six thyroid lesions were immunohistochemically evaluated for HBME-1 and Galectin-3 expression including nodules with cytological atypia, the latter defined as nuclear features suggestive but not diagnostic of papillary thyroid carcinoma. Thirty nodules with cytological atypia, 49 papillary thyroid carcinomas (PTCs), 4 follicular carcinomas and 13 oxyphilic tumors were examined. Forty-one of the 49 PTCs, 16 atypical thyroid nodules and 3 non-malignant oxyphilic tumors exhibited a combined expression of HBME-1 and Galectin-3. In 6 of the sixteen atypical thyroid nodules the immunoreactivity for both markers was strong and diffuse, simulating the pattern observed in PTC. We conclude that thyroid nodules with cytological atypia and strong/diffuse positivity for both HBME-1 and Galectin-3, two well recognized markers of PTC, represent a starting phenotypic change towards PTC, for which a benign or borderline counterpart has not yet been defined. The expression of HBME-1 and Galectin-3 in some thyroid nodules is related to the presence of cytological atypia suggestive but not diagnostic of PTC. The phenotypic similarity between this subset of thyroid nodules with cytological atypia and PTC is also confirmed by our data according to which Galectin-3 and HBME-1 have been found to be highly sensitive for PTC.

Myxoid monophasic synovial sarcoma: case report of an unusual histological variant.

We report the case of a 61-year-old woman who presented a recurrent myxoid synovial sarcoma involving the right ankle and foot. This tumor, defined as a synovial sarcoma showing more than 50% myxoid change in the stroma, has only recently been described as a rare histological variant. The histological diagnosis is particularly difficult in such cases, as the one we are describing, where the tumor is entirely myxoid and monophasic raising the possibility of other myxoid soft tissue neoplasms, such as extraskeletal myxoid chondrosarcoma, malignant peripheral nerve sheath tumor or leiomyosarcoma. On the basis of morphological and immunophenotypical findings, the diagnosis of myxoid synovial sarcoma should be properly established, especially in view of its unusual clinical course and treatment. Furthermore, we will discuss the clinicopathological and immunohistochemical features observed in our case.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Sex steroid modulation of neurohypophysial hormone receptors in human nonpregnant myometrium.

Neurohypophysial hormone receptors were studied in myometrial specimens obtained from nonpregnant women using binding and in vitro contractility studies. The mathematical modeling of self- and cross-competition curves among [3H]oxytocin (OT), [3H]arginine vasopressin, the V1 vasopressin (VP) antagonist [3H]d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and the OT agonist [Thr4, Gly7] OT strongly indicates the presence of multiple classes of OT and arginine vasopressin receptors. The latter show the same pharmacological characteristics as the neurohypophysial hormone receptors described by our group for the human pregnant myometrium; in addition, they regulate the contractility of uterine strips. Blocking experiments were performed to evaluate the relative OT and V1 VP receptor distribution in 30 uterine specimens obtained from normal cycling and postmenopausal women. The glucuronoconjugate metabolites of 17 beta-estradiol and progesterone were also measured in 16 patients in early morning urine samples taken the same day as surgery. Our results show that V1 VP receptors are not only present but also biologically active in all the uterine specimens studied with virtually equal density in normal cycling and postmenopausal women. However, their concentrations do not correlate with either estrogen or progesterone urinary levels. The lowest OT receptor density was found at mid-cycle and in menopause, independently of any correlation with the urinary estrogens. Conversely, OT receptors rise sharply in the late luteal phase and during menstruation. In addition they show a positive relationship with glucuronoconjugate metabolites of progesterone levels. These results indicate that progesterone does not inhibit the expression of uterine OT receptors in the human uterus. Furthermore, they imply that neurohypophysial hormones are involved in the control of uterine activity during the menstrual cycle.

Human myometrium during pregnancy contains and responds to V1 vasopressin receptors as well as oxytocin receptors.

We have recently demonstrated the presence of two classes of neurohypophysial hormone receptors in the vagina, myometrium, and oviduct of rabbit: an oxytocin (OT) site and a V1 arginine vasopressin (AVP) site. We now report binding and in vitro contractility studies on human myometrial specimens obtained at cesarean section from women at the end of pregnancy. The program Ligand was used to analyze self- and cross-displacement curves for labeled OT, AVP or its V1 antagonist d(CH2)5TyrMeAVP, the corresponding unlabeled peptides, and selective analogs. Our results clearly indicate the presence of heterogeneity of binding sites in human uterus. Blocking experiments were performed to evaluate the density of OT and V1 AVP receptors in individual uterine specimens. The contractile response of the same samples to OT, AVP, and analogs was also evaluated. Our results indicate that V1 AVP receptors are present in all of the uterine specimens investigated, with virtually equal density from 32 weeks to term. AVP and the V1-selective agonist [Phe2,Ile3,Orn8]VP stimulate contractility of uterine strips, an effect blocked by nanomolar concentration of the V1 antagonist d(CH2)5TyrMeAVP. Uterine OT receptors increase during late pregnancy, peaking in early labor. A significant correlation between the density of OT receptors and the frequency of uterine contractions (external tocography) was found in pregnant women before surgery. OT stimulated in vitro contractility of uterine strips only when the density of receptors was more than 150 fmol/mg protein. In conclusion, we identified biologically active V1 AVP receptors in human uterus at the end of gestation and confirmed the primary relevance of OT receptors in human parturition.

Management of benign adnexal masses by vaginal route.

Until recently, surgical treatment of a benign adnexal mass implied a laparotomy. In recent years, the development of laparoscopic surgery, as well as ultrasound-guided aspiration techniques, have significantly modified the treatment options for these patients. These procedures have shown considerable advantages. They have reduced surgical trauma and have shortened the hospital stay. We present the results of our experience on the feasibility of a trans-vaginal surgical approach for the removal of benign adnexal masses. This technique, using traditional and cheap surgical instruments, allows the surgeon to excise benign adnexal masses, by entering the peritoneum through the posterior vaginal fornix and thus avoids the trauma of laparotomy. Fifty-four patients were operated on by this technique at our Department. The mean age was 39 years (range 21-66). In all cases, the operation was completed by the trans-vaginal approach. The median operative time was 30 minutes (range 20-45), and no blood transfusion was needed. The pathological diagnoses were as follows: functional ovarian cyst; 19, endometriotic cyst; 18, dermoid cyst; 11, parovarian cyst; 4 and peduncolated fibroid of the uterine fundus; 2 cases. The diameter of the adnexal masses ranged from 3 to 10 cm (median of 6 cm). In 30 cases, a conservative surgery was done (including 2 myomectomies), whereas in 24 cases, the adnexectomy was needed. Median post-operative stay in hospital was 4 days (range 1-14). This study shows the feasibility of trans-vaginal surgical approach for benign adnexal masses. The advantages and limitations of this technique, as well as of the traditional and laparoscopic surgery are considered and discussed. We believe that the transvaginal approach could be useful and cost-effective for the treatment of selected cases of adnexal masses.

Nimesulide in the treatment of mastalgia.

Sixty patients with mastalgia, either idiopathic or secondary to dysplastic lesions, were treated with oral nimesulide (100mg tablets twice daily) for 15 days. Breast tension and pain, assessed at baseline and on completion of the treatment period, improved or resolved with therapy. Indeed, breast pain (which most likely manifests as a consequence of periductal inflammation) was most noticeably reduced. The drug was well tolerated in nearly all patients. These results support the usefulness of nimesulide and other nonsteroidal anti-inflammatory drugs in the treatment of mastalgia.

Relationship between leptin and oestrogens in healthy women.

OBJECTIVE: Leptin. a protein secreted by white adipocytes, plays a relevant role in the regulation of body weight and food intake. A possible role for sex hormones in the regulation of leptin secretion has been suggested; however, the effect of variations in oestrogen concentration on serum leptin levels has not been described so far. METHODS: In study 1, serum leptin concentrations were measured on days 3, 10, 17 and 24 of the menstrual cycle in 18 healthy, lean, regularly menstruating women, aged 18-35 years. Serum oestradiol, progesterone, testosterone. Delta4-androstenedione, dehydroepiandrosterone sulphate (DHEAS). LH and FSH concentrations were also determined. In study 2, serum leptin and oestradiol levels were measured on the 5th and 7th day of ovarian stimulation with human FSH (225 IU daily) during an in vitro fertilisation programme for infertility in 20 women aged 25-45 years. RESULTS: The results from study 1 show a physiological fluctuation of leptin levels during the menstrual cycle, which has not been described previously. Leptin levels are significantly lower in the early follicular phase. The results of study 2 show a parallel increase in serum oestrogen and leptin concentrations during FSH administration. CONCLUSIONS: The fluctuation in leptin levels during the menstrual cycle observed in study 1 is compatible with the hypothesis of a stimulatory effect of oestrogen on leptin secretion. The results of study 2 support the hypothesis of a relevant role for oestrogen in the regulation of leptin secretion. Leptin fluctuations during the menstrual cycle are consistent with reported perimenstrual variations in food craving and consumption.

Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma.

The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.

Pathogenesis and pathology of liver disease associated with alpha 1-antitrypsin deficiency.

alpha 1-Antitrypsin (alpha 1-AT) accumulates in the rough endoplasmic reticulum through a mechanism of polymerization. Polymerization is favored by the incorrect tertiary structure of the alpha 1-AT caused by a point mutation at position 342 of the protein. Accumulation of alpha 1-AT in the liver cells (and in hepatocytes and colangiocytes) is not sufficient per se to explain the liver disease that is manifested in a minority of PiZ subjects and thus, a trigger factor must be hypothesized. A virus (hepatitis C virus or some other kind of virus not identified as yet) is among the most probable trigger factors. In Z subjects (among the general population), relevant liver disease is probably a more rare event than thought in the past and most of these subjects escape major liver disease. Usually, liver disease is not a significant problem in patients with COPD.

Fibrolamellar carcinoma of the liver: the malignant counterpart of focal nodular hyperplasia with oncocytic change.

A case of fibrolamellar carcinoma (FLC) in a noncirrhotic liver of a 20-year-old man is described. Gross features and the presence, among the tumor cells, of bile ducts, of thick-walled blood vessels and nerves, and, ultrastructurally, of myofibroblast-like cells are the most significant findings, suggesting that FLC is the malignant counterpart of focal nodular hyperplasia with oncocytic change. Histochemical and immunohistochemical methods demonstrate the presence inside the oncocytic tumor cells of copper, copper-binding protein, and alpha 1 antitrypsin. The pathogenesis and the significance of these findings then are discussed and related to the restricted capacity of oncocytic cells to fulfill normal cellular function.

Alpha-1-antitrypsin (AAT) deposits in gall bladder adenocarcinoma and liver in partial AAT deficiency (Pi SZ phenotype).

Alpha-1-antitrypsin (AAT) immunoreactive inclusions were found in an adenocarcinoma of a gall bladder of a patient with Pi SZ phenotype who also had globular AAT accumulation in the liver. The inclusions did not react with antibodies against other plasma proteins, thus suggesting a primary synthesis of AAT in these cells. The presence of AAT in the tumor cells may represent resurgence of an oncofetal antigen, or, indirectly, may mean that AAT-containing cells normally exist in the human non-neoplastic gall bladder. The accumulation of AAT in tumor cells might be a basic process in malignant transformation.

Alpha-1-antitrypsin phenotypes in malignant lymphoma.

The alpha-1-antitrypsin (alpha 1 AT) Pi phenotypes have been determined by isoelectric focusing in a series of 228 patients having a histologically diagnosed malignant lymphoma and in 250 healthy controls. The Pi MZ phenotype occurred in 13 patients with lymphoma (5 . 8%) and in five of 250 healthy individuals (2%). Furthermore, one patient with a Pi SS and three patients with an abnormal unknown phenotype, migrating slower than Z, were found in the lymphoma group. No prevalence for a special lymphoma type was observed among the abnormal Pi phenotype patients. The increased incidence of abnormal Pi phenotypes in malignant lymphoma's support the hypothesis of the possible role of alpha 1 AT in development of immunopathological disorders.

Giant pelvic retroperitoneal liposarcoma.

BACKGROUND: Pelvic retroperitoneal liposarcomas are rare in young women (under 30 years old). We present a case of a giant well-differentiated liposarcoma of the retroperitoneum in a young woman. CASE: A 27-year-old nulligravida presented with rapid abdominal enlargement. Pelvic examination found a huge mass extending from the left adnexa to the epigastric region. At surgery, the pelvic organs were displaced to the right side by a retroperitoneal mass that marginally involved the left fallopian tube. The left ovary, uterus, and right adnexa were not involved and were not removed. No adjuvant irradiation was given. The patient was alive and well 2 years after the operation and was 23 weeks pregnant. CONCLUSION: Gynecologists should be familiar with pelvic retroperitoneal liposarcomas and their treatment.

Intestinal anastomosis with the biofragmentable anastomosis ring.

BACKGROUND: The fear of anastomotic complications prevents the spread of the use of the biofragmentable anastomosis ring (BAR) in intestinal surgery. PATIENTS AND METHODS: A total of 453 patients underwent intestinal resection and anastomosis with the BAR. RESULTS: In all, 514 anastomoses have been carried out, 424 (83%) in elective settings, and 90 (18%) in emergency. Fifty-one patients had multiple anastomoses. Reoperation was performed in 4 patients (1%) who had a complete anastomotic leakage. In 13 patients (3%), anastomotic leakage was partial, and only 1 patient required reoperation. No postoperative intestinal obstruction occurred. Four patients (1%) developed late anastomotic strictures, which have been treated by endoscopic dilation. CONCLUSIONS: The results of our experience and those of other large clinical series definitely confirm the effectiveness of the BAR method, which seems to be a standard, easy, rapid, and safe technique either in elective or emergency surgery.

A national program for detection of alpha 1-antitrypsin deficiency in Italy. Gruppo I.D.A.

alpha 1-antitrypsin (AAT) deficiency is an inherited condition characterized by low serum levels of AAT and an increased risk of developing pulmonary emphysema. The disease occurs mainly in Caucasians, but Southern Europe, including Italy, is considered a low prevalence area. We developed a national program in Italy in order to improve our knowledge of the epidemiology of AAT deficiency and to establish a registry of the AAT-deficient individuals. The program had two phases: the first lasted 36 months, during which blood from coupons mailed by respiratory physicians from throughout the country, was isoelectrofocused by the Central Laboratory in Rome. The second phase started in February 1996, and the Registry was established. Up to August 1998, 151 subjects with AAT deficiency have been identified and 64 have been enrolled in the Registry. We believe that such a program plays a crucial role in identifying AAT deficiency in a country such as Italy, with low prevalence and low awareness of this rare condition.