IgG-lambda secreting B-lymphoplasmacytic lymphoma with disseminated cutaneous infiltration: report of a rare case.

We present an 85-year-old female with IgG-lambda lymphoplasmacytic lymphoma (LPL) with disseminated cutaneous infiltration during disease progression, 9 months after initial diagnosis. The patient was voluntarily undertreated, therefore the disease progressed with vast cutaneous involvement. The patient died from severe sepsis and disseminated intravascular coagulation due to acute respiratory bacterial infection, before receiving any kind of treatment.

Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas.

The expression of mitosin, a novel proliferation-associated molecule was evaluated immunohistochemically in a consecutive series of 47 patients with primary intracranial benign and atypical meningiomas. Mitosin expression was correlated with proliferation markers Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA), topoisomerase IIalpha (TopoIIalpha) and mitotic index, as well as with standard clinicopathological parameters and patient outcome. Seven tumors recurred (14.8%) following gross total resection, within a follow-up period ranging from 21 to 108 months (median 60 months). The higher proliferation indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha. Mitosin labeling index (LI) ranged from 0.1 to 57% (median 3%), with a significant overlapping of values between grades. A significant positive correlation was shown between mitosin LI on the one hand and Ki-67 LI (p < 0.001), or the mitotic index (p = 0.027) on the other. The incidence of recurrence was higher in cases with a mitosin LI higher than 3% (p = 0.048). Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened recurrence-free survival. In multivariate analysis, the labeling indices of mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to provide independent prognostic information, beyond that obtained by standard clinical and pathological parameters. However, as indicated by factor analysis, the prognostic information yielded by mitosin was superior to that provided by the remaining proliferation markers (p = 0.041). We conclude that mitosin immunohistochemical expression, although failing to discriminate between benign and atypical meningiomas, may be of use as a novel cell proliferation marker and as a predictor of tumor recurrence.

Elevated expression of the myc gene in human benign and malignant breast lesions compared to normal tissue.

Expression of the c-myc gene in human breast lesions and in adjacent normal tissue was studied by immunohistochemical analysis. The previously described monoclonal antibody Myc1-9E10 (1) which recognizes the p62 c-myc protein was used in paraffin tissue sections. A total of 101 cases of breast disease examined included 38 simple and complex cystic disease, 18 simple and hyperplastic fibroadenomas, 36 ductal and lobular carcinomas and 9 in situ carcinomas. Whereas the adjacent normal tissue was slightly positive, 25 out of 38 cystic disease, 7 out of 18 fibroadenoma, 36 out of 36 carcinoma and 9 out of 9 in situ carcinoma specimens showed moderate to high levels of p62 c-myc expression as indicated by staining intensity. These results suggest that the c-myc protein may play a role in breast neoplasia.

Giant cell fibroblastoma: an entity or a reactive phenomenon?

The histological and immunohistochemical features of four tumors displaying the characteristic pattern of Giant Cell Fibroblastoma (GCF) are presented. Three of them were found in association with classical and/or myxoid dermatofibrosarcoma protuberans, while the fourth tumor was a retroperitoneal malignant hemangiopericytoma where foci with features of GCF were found. Typical sinusoidal spaces and the bizarre mononuclear and multinucleated cells in close association to blood vessels presenting a wide spectrum of lesions of their walls are also described. These last changes led us to believe that GCF-like lesions might not always characterize an entity but could often represent a host reaction of the connective tissue to locally aggressive or malignant tumors.

Immunohistochemical study of ras and myc oncoproteins in apocrine breast lesions with and without papillomatosis.

We have previously employed different immunohistochemical procedures for the study of breast disease in the human. The use of the monoclonal antibodies (M. Abs) against protein products of the ras and c-myc oncogenes has shown that the respective oncoproteins are expressed not only in the cancer cases but also in the majority of complex cystic diseases (C.C.D.). The term C.C.D. is used when cystic disease is associated with epithelial hyperplasia and cellular atypia but without malignant transformation. Additionally, the degree of staining intensity is increasing when the latter is associated with papillary apocrine metaplasia, which is included in the group of epithelial hyperplasias. In the present study we examined 50 cases of C.D. 20 of which were present in infiltrating duct carcinomas of non otherwise specified (NOS) type and the remaining 30 concerned benign biopsy material. We divided C.D. into simple (S.C.D.) and complex (C.C.D.) and we focused our interest on the presence or absence of papillary hyperplasia in apocrine metaplastic lesions. The whole material (50 cases) was examined immunohistochemically for the c-myc p62 protein using the M.Ab. Myc 1-9E10, and 21 cases were also examined for the ras p21 protein using the M.Ab. Y13 259. Our results imply that the great majority of C.D. show elevated expression of both c-myc p62 and ras p21 when associated with apocrine metaplastic papillary proliferations. Our results suggest that the levels of the expression of ras and myc oncoproteins may serve as premalignant markers for the prevention of the disease.

Immunohistochemical study of ras oncogene expression in endometrial and cervical human lesions.

The Y13 259 monoclonal antibody to the ras p21 protein was used in an immunohistochemical assay to study the levels of ras p21 in human uterine lesions as compared to normal tissue. Out of 73 hysterectomies obtained we have examined ras p21 expression in separately made sections from the endometrium, the cervix and leiomyomas found in the same specimens. A total of 155 tissue sections were finally evaluated and included: 55 endometrial mucosae (normal, hyperplastic and atrophic), 13 leiomyomas, 60 cervicitis (mild, moderate and severe with or without dysplasia), 3 in situ and 7 invasive carcinoma of the cervix, 12 invasive adenocarcinoma of the endometrium and 5 endometrial adenocarcinomas, which involved the cervical canal. Out of the 73 hysterectomy specimens 27 lesions were malignant and showed elevated expression of ras p21. The remaining 128 were normal or atrophic mucosae and benign or premalignant lesions, which were mostly negative. However, all cases of severe cervicitis and dysplasias and 6 out of the 12 hyperplastic endometrial lesions were found to be moderately or highly positive. Our results suggest that elevated expression of ras oncogenes may play an important role in the development of human uterine lesions.

Chromosome aberrations and expression of ras and myc oncogenes in leiomyomas and a leiomyosarcoma of the uterus.

Twenty eight leiomyomas and one leiomyosarcoma were cytogenetically analysed and also examined for ras and myc oncoprotein expression. Chromosome alterations were found in seven leiomyoma cases. In four of them 12q14-15 was involved. P21 product of H-ras and P62 product of c-myc genes were detected in paraffin embedded parallel tissue sections. A high expression of H-ras was apparent in most tumors. C-myc expression was weak or negative in most leiomyomas with normal karyotype while on the contrary in three out of seven cases with abnormal cytogenetic findings the gene product stained moderately positive. Considerable chromosome abnormalities and oncogene overexpression were also identified in the leiomyosarcoma.

[Breast cancer in adipose breasts]. / Cancer mammaire des seins adipeux.

The authors have studied breast cancer in fatty breasts in an attempt to prove their observations that Wolfe's classification "N1" on mammography was not necessarily "normal". Two groups of women, the first called group "A" consisting of 384 women with cancer of the breast, and group "B", the control group of 400 women who had no abnormality in the breast, were studied and correlated for epidemiological, thermographic, mammographic, and anatomo-pathological parameters. The following epidemiological factors were studied: age, marital status, profession, age at menarche and at menopause, menstrual behaviour, age at the first pregnancy that went to term, parity (live and still births), type of delivery, length of breast feeding, number of abortions, use of hormones, and family history of cancer of the breast. In the thermographic studies: the topography of the heat pattern, the primary pathological signs and the thermic state were studied. In mammography: the mammographic appearance after Wolfe and the presence of microcalcifications was studied. In group "A" the following histological group parameters were studied: which breast, in which quadrant the nodule was situated, the type of breast the contour and size of the tumour, the number of axillary nodes removed, the histological type of the cancer, the histological grade of the malignancy, vascular invasion, details about the skin and the areola, calcifications, lymphocytic infiltration of the stroma, multicentricity, the co-existence of cystic disease of the breast and invasion of the axillary nodes. All these above-mentioned parameters were correlated with: the age, the existence of previous pregnancies at term, the macroscopic type of the breast and the mammographic type according to Wolfe. The breasts were divided into three macroscopic types: fatty, fibrous and intermediate. The correlation of the mammographic type according to Wolfe showed that types N1 and P1 corresponded to fatty and partially intermediate types. In group "A" the macroscopically fatty as compared with the other type of breasts showed a more extensive degree of infiltrations: vascular (76.5%), skin (90.3%), areolae (88.9%) and lymphocytic (80.1%), as well as a higher percentage of axillary metastases (57.7%).

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

Apoptosis detected with monoclonal antibody to single-stranded DNA is a predictor of recurrence in intracranial meningiomas.

Precise quantitation of apoptotic cells in meningiomas is necessary to determine the role of apoptosis in tumor growth and recurrence. In this study, we investigated the incidence of baseline apoptosis in relation to p53 and bcl-2 protein expression, proliferation status as expressed by Ki-67, PCNA and mitotic counts, standard clinicopathological parameters and patients' outcome, in a series of 59 patients with primary intracranial benign and atypical meningiomas. Seven tumors recurred (11.9%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Tissues consisted of archival formalin-fixed paraffin-embedded meningioma specimens. The apoptotic index (AI) ranged from 0% to 2.90% (mean: 0.50%), increased with proliferative activity (p = 0.014), had lower values in transitional meningiomas (p = 0.001) and was unrelated to grade and p53 expression. Increased AI predominated among bcl-2 negative tumors (p = 0.041) and tended to be accompanied by a shortened recurrence-free survival, in univariate (p = 0.0407) as well as in multivariate analysis (p = 0.0405). These results implicate apoptotic rate in meningioma growth and recurrence and denote that assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valid prognostic information irrespective of other parameters.

Soft tissue angiomyolipoma. A case report.

A unique case of angiomyolipoma developed in the deep soft tissues of the lower extremity of a 79 year old woman is presented. The initial tumor was misinterpreted as an ordinary lipoma and the recognition of the entity was accomplished only in the recurrent tumor and after the re-evaluation of the slides from the former tumor. The extensive fibroplasia and the bizarre appearance of many proliferating fibroblasts found in the recurrent tumor have been attributed to local host reaction and degenerative changes. However, these changes may create an alarming histologic pattern to the tumor, which need to be differentiated from a lipo- or leiomyosarcoma.

DNA topoisomerase IIalpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas.

AIMS: To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome. METHODS AND RESULTS: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. CONCLUSIONS: TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.

Hormone receptors in non-malignant meningiomas correlate with apoptosis, cell proliferation and recurrence-free survival.

AIMS: A retrospective immunohistochemical and statistical analysis of patients with non-malignant meningiomas was undertaken to determine the correlation of steroid hormone receptor status with apoptosis, tumour cell proliferation, clinicopathological characteristics and prediction of recurrence. METHODS AND RESULTS: Paraffin sections from 51 primary intracranial totally resected benign and atypical meningiomas were immunohistochemically evaluated for the expression of progesterone (PR), oestrogen (ER) and androgen (AR) receptors, apoptotic rate, Bcl-2, p53 and Ki67 antigens. In addition to the above parameters, the mitotic index and the patients' clinicopathological data were statistically correlated and entered in a recurrence-free survival analysis. A high level of apoptotic cell death was associated with loss of PR expression by logistic regression analysis (P = 0.016). An inverse correlation existed between the mitotic index and PR counts (P = 0.009), while high Ki67 values correlated with increased ARs (P = 0.041). Atypical meningiomas had a lower ER staining score (P = 0.036). Multivariate analysis indicated that the absence of PR and large tumour size were significant factors for shorter disease-free intervals. CONCLUSIONS: The results suggest that ER expression is lost or reduced in atypical meningiomas, whereas loss of PR expression is an indicator of increased apoptosis and early recurrence. PRs and ARs may also influence tumour cell proliferation.