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.

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.

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.

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.

Primary small cell neuroendocrine carcinoma of the breast.

We report and characterize immunohistochemically a case of primary small cell neuroendocrine carcinoma of the breast. The tumor, which arose in the left side, was 18 cm in maximum diameter and microscopically was composed of patternless sheets of undifferentiated small cells with a high nuclear-to-cytoplasmic ratio, hyperchromatic nuclei with indistinct cytoplasm, inconspicuous nucleoli, numerous mitotic figures and large areas of coagulative necrosis. Tumor cells were positive for bcl-2, neuron-specific enolase, synaptophysin, CAM 5.2 and cytokeratin AE1/3, but negative for LCA, CD30, HMB-45, chromogranin A, estrogen receptor, progesterone receptor, Her-2/neu and CD99. The opposite breast harboured an intraductal carcinoma with a focus suggesting microinfiltration, a finding never reported before. In this paper we have also extensively reviewed the literature on the subject, emphasizing the variable immunohistochemical profile and the aggressiveness of mammary small cell carcinoma. The rapidly fatal clinical course of our case, which appears to have the largest dimensions described in literature, underlines the importance of an early diagnosis and treatment for long-term survival.

Evaluation of galectin-3 expression by sarcomas, pseudosarcomatous and benign lesions of the soft tissues. Preliminary results of an immunohistochemical study.

Galectin-3 is an endogenous galactose-binding protein that is expressed in several normal and neoplastic tissues and is thought to play a role in a variety of biological processes. In this study we have examined the immunohistochemical expression pattern of galectin-3 in the most representative categories of soft tissue tumors consisting of 162 patients' specimens. Lesions were classified according to histogenetic criteria into 13 major categories. Overall, there were 18 fibrous tumors (13 benign, 4 intermediate and 1 malignant), 21 fibrohistiocytic tumors (5 benign, 11 intermediate and 5 malignant), 22 lipomatous tumors (14 benign and 8 malignant), 20 smooth muscle tumors (12 benign, 5 intermediate and 3 malignant), 2 skeletal muscle tumors (2 malignant), 19 vascular tumors (9 benign and 10 malignant), 6 perivascular tumors (5 benign and 1 malignant), 7 synovial tumors (4 benign and 3 malignant), 3 benign mesothelial tumors, 27 neural tumors (25 benign and 2 malignant), 7 cartilaginous and osseous tumors (4 benign and 3 malignant), 8 miscellaneous tumors and 2 high grade unclassified sarcomas. Galectin-3 was constantly expressed by almost all the major categories of benign, pseudosarcomatous and malignant soft tissue tumors. At this time no data are available in the literature about the expression of galectin-3 distribution in a wide range of soft tissue tumors. In the present work we discuss the significance and the possible usefulness of such findings.

Passive smoking and lung function in alpha(1)-antitrypsin heterozygote schoolchildren.

BACKGROUND: A study was performed to determine whether Pi heterozygotes exposed to smoking have a higher risk of reduced lung function than Pi M homozygotes. METHODS: The effect of passive smoking on lung function was investigated in a cross sectional study of 997 primary and secondary schoolchildren aged 11-13 years categorised by Pi phenotype as either PiM homozygotes or Pi heterozygotes. Data on respiratory health and risk factors were collected by questionnaire, lung function was measured by spirometric tests, bronchial hyperresponsiveness was evaluated by methacholine test, atopic status was evaluated by skin prick testing, and a blood sample was collected to determine Pi phenotype. Urinary cotinine and creatinine concentrations were determined and assessment of exposure was made from questionnaire data and urinary cotinine concentrations. The results were analysed by multiple regression analysis. RESULTS: Sixty one subjects (6.1%) were found to be Pi heterozygotes. Lung function did not differ between homozygotes and heterozygotes. There was a reduction in lung function in subjects exposed to parental smoking in the overall sample: FEV(1)/FVC ratio (-0.78%), FEF(25-75) (-0.11 litres), and FEF(75) (-0.13 litres). Interaction terms between parental smoking and Pi status were significant with regard to FEV(1)/FVC ratio (p=0.035) and FEF(50) (p=0.023). In subjects exposed to parental smoking the decrement in lung function in Pi heterozygotes tended to be greater (FEV(1)/FVC ratio = -2.57, FEF(25-75) = -0.30, FEF(50) = -0.43, and FEF(75) = -0.29) than in PiM homozygotes. These results did not change significantly when the urinary cotinine concentration was used as an exposure variable. CONCLUSIONS: The detrimental effect of environmental tobacco smoke on lung function in schoolchildren is confirmed. This harmful effect is greater in Pi heterozygotes than in PiM homozygotes.

Melanocytic dysplasia and multiple melanoma of the vulva.

We report a case of a 24-year-old woman with multiple pigmented lesions on her vulva. Histologically the lesions showed a heterogeneous pattern: the majority consisted of melanoma in situ and invasive melanoma; in a few lesions a much less clear-cut picture was found with only melanocytic dysplasia of various degrees. Our case shows the relationship between anomalous melanocytic proliferation of the vulva and vulvar melanoma and underlines the necessity of a thorough check of all melanocytic vulvar lesions also in young patients.

Galectin-3, a marker of well-differentiated thyroid carcinoma, is expressed in thyroid nodules with cytological atypia.

AIMS: The distribution of galectin-3, a widely recognized marker of well-differentiated thyroid carcinoma, was investigated in 95 thyroid lesions including nodules with foci of cytoarchitectural atypia. METHODS AND RESULTS: Twenty-eight papillary carcinomas, five follicular carcinomas, one Hurthle cell carcinoma, three poorly differentiated carcinomas, one anaplastic carcinoma, 25 nodular hyperplasias and 27 follicular adenomas, including nodules with atypical features, three neoplasms of undetermined malignant potential and two thyroiditis cases were examined. By immunohistochemistry, galectin-3 was consistently found in carcinomas; otherwise benign nodules exhibited galectin-3-positive clusters of cells with poorly developed features of differentiated carcinoma (mainly of papillary type) such as nuclear chromatin clearing, nuclear clefting, pseudoinclusions, which, in each case, were not histologically sufficient to warrant a definitive diagnosis of malignancy. In other nodules galectin-3 staining was negative. The latter were either clearly benign or showed constantly a minor degree of chromatin clearing and of other atypical features when compared with galectin-3-positive cases. CONCLUSIONS: Galectin-3, a reliable marker of differentiated thyroid carcinoma as confirmed in our series of malignant neoplasms, appears expressed in nodules with an overall benign appearance but with focal areas suspicious for malignancy. The significance of such findings needs to be further investigated.

Radical vaginal hysterectomy: classic and modified.

RVH offers significant advantages to the corresponding abdominal procedure, including: the possibility for regional anesthesia, particularly in patients with poor medical conditions; reduced surgical trauma because of the absence of an abdominal incision; applicability in obese patients; shorter surgical time when performed by an experienced surgeon; decreased need for blood transfusions; lower risk for complications; faster postoperative recovery period; shorter hospitalization. The primary drawback to the use of RVH for early stage cervical cancer has always been the lack of lymph node dissection. This has now been modified by the widespread use of laparoscopic lymphadenectomy. The increasing reliability of noninvasive radiologic techniques has provided and will continue to provide greater possibilities for preoperative staging to best determine the needs of the patient. The authors believe that an oncologic surgeon familiar with advanced laparoscopic techniques and RVH is able to take advantage of the benefits of both routes. Furthermore, a surgeon skilled in these techniques and RAH has the tools to ideally care for the specific needs, of each patient. The authors encourage individualization of surgical management, with special emphasis on the revision of the role of RVH in gynecologic oncology.

Rare presentation of carcinosarcoma arising in bladder diverticulum.

An 87-year-old man presented with hematuria and dysuria. An endoscopic examination revealed a bladder mucosa which was almost entirely occupied by diverticula. On the left lateral wall of the bladder there was a huge diverticulum which contained a 12 cm mass extending beyond the bladder wall in the extraperitoneal tissues. Upon histological examination the mass proved to be a carcinosarcoma which was composed by a squamous carcinoma and a sarcoma resembling a malignant fibrous histiocytoma. The two components, i.e. carcinomatous and sarcomatous, were separated by a sharp collision border and no intermingling was ever noted. The epithelial component showed immunoreactivity for cytokeratin and EMA, while the mesenchymal component was diffusely reactive for vimentin, alpha-1-antitrypsin and lysozime. Both components were reactive for galectin-3, whereas S100, desmin and smooth muscle actin were negative. This is the fourth reported case of carcinosarcoma originating in a bladder diverticulum.

Spitzoid malignant melanoma in teenagers: an entity with no better prognosis than that of other forms of melanoma.

AIMS: A rare form of melanoma in teenagers closely simulates Spitz naevus and is claimed to have a good prognosis. The aim of this study is to identify the clues for a confident diagnosis of this entity and to confirm the peculiarly good prognosis. METHODS AND RESULTS: Two cases of melanoma with Spitzoid features were compared with Spitz naevus and it was found that the major distinctive criteria are: mitoses and single cell necrosis in the deepest part of the lesion, cellular and particularly nuclear and nucleolar pleomorphism, and growth pattern in solid sheets of cells. More subtle clues were the asymmetric distribution of pigment and the thinning of the epidermis with parakeratosis and exudate in the cornified layer. Both of the lesions reached the mid-dermis. There was a fatal outcome in both patients after generalized metastatic spread. The metastatic disease in one of the cases appeared 15 years after the excision of the primary lesion. CONCLUSIONS: Spitzoid melanoma in teenagers can be distinguished from Spitz naevus if strict criteria are followed. Spitzoid melanoma does not show a better prognosis than other types of melanoma if the follow-up is prolonged enough.

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.