[Laugier-Hunziker syndrome : A rare differential diagnosis of mucocutaneous hyperpigmentation]. / Laugier-Hunziker-Syndrom : Eine seltene Differenzialdiagnose der mukokutanen Hyperpigmentierung.

Laugier-Hunziker syndrome (LHS) is characterized by lentiginous hyperpigmentation of the oral mucosa and lips. In addition, longitudinal melanonychia and palmoplantar hyperpigmented lesions may occur. LHS is a clinical diagnosis of exclusion. Herein, we report the case of a 66-year-old woman with LHS. The clinical and histopathologic features of LHS are presented and important differential diagnoses are discussed.

Prognostic relevance of the loss of stromal CD34 positive fibroblasts in invasive lobular carcinoma of the breast.

CD34+ fibroblasts are constitutive stromal components of virtually all organs, including the mammary stroma, being involved in matrix synthesis, antigen presentation, and tumor-associated stromal remodeling. The most common subtype of invasive breast carcinoma, invasive carcinoma of no special type (IBC-NST), is known for its stromal loss of CD34+ fibroblasts while acquiring alpha smooth muscle actin-positive (α-SMA+) myofibroblasts, i.e., cancer-associated fibroblasts (CAF), whereas invasive lobular carcinoma (ILC) displays partial preservation of CD34+ fibroblasts. The aim of this study was to evaluate the prognostic relevance of stromal CD34+ fibroblasts and α-SMA+ myofibroblasts in an extended collection of ILC. A total of 133 cases of ILC, primarily resected between 1996 and 2004 at University Hospital Marburg, were examined semiquantitatively for stromal content of CD34+ fibroblasts and α-SMA+ myofibroblasts. Partial preservation of CD34+ fibroblasts in the tumor stroma of ILC was confirmed. Absence of CD34+ fibroblasts in the tumor stroma significantly correlated with the presence of α-SMA+ myofibroblasts (p = 0.010), positive lymph node status (p = 0.004), and pN stage (p = 0.006). Stromal loss of CD34+ fibroblasts was significantly associated with lower overall and disease-free survival rates (p = 0.012 and 0.013, respectively). Multivariate analysis adjusted for pT and pN stage revealed stromal loss of CD34+ fibroblasts as independent prognostic parameter (p = 0.05). To our knowledge, this is the first report defining prognostically relevant stromal subtypes of ILC with long-term follow-up. Future research targeting the potential diagnostic and therapeutic implications of CD34+ fibroblasts and CAF in breast cancer, especially ILC, is a promising field of interest.

Growth of transgenic RAF-induced lung adenomas is increased in mice with a disrupted PPARbeta/delta gene.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors with essential functions in regulating lipid metabolism. Both the PPARbeta (also referred to as PPARdelta) and PPARgamma subtype have been reported to either attenuate or potentiate tumorigenesis in a number of different models of intestinal and skin carcinogenesis. In the present study, we have addressed the role of PPARbeta and PPARgamma in lung tumorigenesis in a transgenic mouse model of RAF-induced lung adenoma using two different strategies: i) crossing with PPARbeta null mice, and ii) chronic treatment with the PPARgamma agonist rosiglitazone. Histological examination revealed a significant enhancement of tumor growth in mice lacking one or both alleles of Pparb, but no significant effect in response to rosiglitazone. These observations indicate i) that RAF-induced lung tumorigenesis is attenuated in mice with a disrupted Pparb gene, and ii) that chronic PPARgamma activation does not affect lung adenoma growth. These results are relevant with respect to the clinical application of drugs modulating the activity of PPARbeta or PPARgamma.

CD34+ fibrocytes are preserved in most invasive lobular carcinomas of the breast.

It is generally agreed that invasive carcinomas of the breast consistently lack stromal CD34+ fibrocytes. The pertinent literature shows that this assumption is well based for invasive ductal carcinomas, but evidence of loss of stromal CD34+ cells in lobular carcinomas is weak. We present a series of 22 invasive lobular carcinomas (ILCs) which, in contrast to invasive ductal carcinomas, display a gradual reduction of stromal CD34+ fibrocytes. One third of the study population showed a completely preserved population of CD34+ fibrocytes, in another third, this cell population was reduced in comparison to normal breast tissue, and in the remaining third, loss of CD34+ fibrocytes comparable to that occurring in virtually all invasive ductal carcinomas was found. The present study shows that loss of CD34+ fibrocytes is not a consistent feature of invasive carcinomas of the breast. Therefore, a preserved CD34+ stromal cell population does not exclude malignancy, and analysis of the stromal CD34 expression should be handled with care when used as a diagnostic tool.

CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions.

Besides its function as a matrix-producing cell, the CD34+ fibrocyte has been reported to be an antigen-presenting cell capable of priming naive T cells in situ. Therefore, it has been claimed that the CD34+ fibrocyte may play an important role in host response to tissue damage. The objective of the present study was to analyze the presence and distribution of CD34+ fibrocytes and smooth muscle actin (SMA) reactive myofibroblasts in relation to the underlying pancreatic disease. We investigated a total of 12 pancreatic adenocarcinomas, 7 endocrine tumors of the pancreas, and 8 cases of chronic pancreatitis; in 11 cases, normal pancreatic tissue was available. The stroma of normal pancreatic tissue harbored diffusely scattered CD34+ fibrocytes. Chronic pancreatitis was characterized by an increased number of stromal CD34+ fibrocytes paralleled by a gain of SMA reactive myofibroblasts which were not observed in the normal pancreatic stroma. The stroma of pancreatic ductal adenocarcinomas and endocrine tumors was devoid of CD34+ fibrocytes or showed at least a focal loss of this cell type, whereas SMA reactive myofibroblasts were detected in both endocrine tumors and adenocarcinomas. We conclude that detection of CD34+ fibrocytes may constitute an adjunctive tool in distinguishing chronic pancreatitis from ductal adenocarcinoma since the absence of this cell population strongly favors a neoplastic process. Moreover, CD34+ fibrocytes and myofibroblasts appear to be involved in stromal remodeling associated with chronic pancreatitis and ductal adenocarcinoma.

CD34+ fibrocytes in invasive ductal carcinoma, ductal carcinoma in situ, and benign breast lesions.

The present study was undertaken in order to elucidate the question of whether the distribution of stromal CD34+ fibrocytes and smooth muscle actin (SMA)-reactive myofibroblasts differs between benign and malignant lesions of the breast. We investigated a total of 31 ductal carcinomas and 27 specimens with benign lesions of the breast (ductal hyperplasia, sclerosing adenosis, fibroadenoma, phyllodes tumor) and compared the distribution of CD34+ fibrocytes and SMA-reactive myofibroblasts. The stroma of normal breast tissue contained CD34+ fibrocytes, whereas SMA-reactive myofibroblasts were absent. All benign breast lesions exhibited stromal CD34+ fibrocytes and few lesions (fibroadenomas and phyllodes tumor) showed additional SMA-reactive myofibroblasts. In invasive breast cancer the stroma was devoid of CD34+ fibrocytes but a varying number of stromal SMA-reactive myofibroblasts was detectable. In the setting of the present study the loss of CD34+ fibrocytes was specific for invasive breast cancer and ductal carcinoma in situ, whereas SMA-reactive myofibroblasts were observed in different benign and malignant lesions. These findings may be helpful tools in distinguishing benign breast lesions (e.g., sclerosing adenosis) from invasive breast cancer and in characterizing stromal remodeling associated with invasive cancer.