Melorheostosis of the Fossa Intercondylaris Femoris - A Case Report and Review of the Literature.

INTRODUCTION: Melorheostosis is a rare benign bone condition characterized by excessive segmental sclerosis of cortical bone being reminiscent of dripping candle wax. It typically affects the long bones and can cause impingement and nerve compression syndromes that may require surgical treatment. CASE REPORT: We report the case of a 49-year-old male patient with a 12-month history of the left-sided knee pain and a concomitant limitation of his left knee flexion to 90 degree. Radiographic and magnetic resonance imaging revealed the typical radiographic appearance of melorheostosis with an extraosseous lesion in the fossa intercondylaris femoris being causative for the limited knee range of motion. Following the resection of the extraosseous part of the lesion through a direct open approach, the patient is pain free with a maximum of 110 degree knee flexion at 12-month follow-up. CONCLUSION: Melorheostosis can present with manifold clinical manifestations that potentially require surgical treatment. Even in patients with a challenging localization of extraosseous lesions, a good to excellent functional outcome is possible.

CUX1 Enhances Pancreatic Cancer Formation by Synergizing with KRAS and Inducing MEK/ERK-Dependent Proliferation.

The transcription factor CUX1 has been implicated in either tumor suppression or progression, depending on the cancer entity and the prevalent CUX1 isoform. Previously, we could show that CUX1 acts as an important mediator of tumor cell proliferation and resistance to apoptosis in pancreatic cancer cell lines. However, in vivo evidence for its impact on pancreatic carcinogenesis, isoform-specific effects and downstream signaling cascades are missing. We crossbred two different CUX1 isoform mouse models (p200 CUX1 and p110 CUX1) with KC (KrasLSL-G12D/+; Ptf1aCre/+) mice, a genetic model for pancreatic precursor lesions (PanIN). In the context of oncogenic KRASs, both mice KCCux1p200 and KCCux1p110 led to increased PanIN formation and development of invasive pancreatic ductal adenocarcinomata (PDAC). In KCCux1p110 mice, tumor development was dramatically more accelerated, leading to formation of invasive PDAC within 4 weeks. In vitro and in vivo, we could show that CUX1 enhanced proliferation by activating MEK-ERK signaling via an upstream increase of ADAM17 protein, which in turn led to an activation of EGFR. Additionally, CUX1 further enhanced MEK-ERK activation through upregulation of the serine/threonine kinase MOS, phosphorylating MEK in a KRAS-independent manner. We identified p110 CUX1 as major driver of pancreatic cancer formation in the context of mutant KRAS. These results provide the first in vivo evidence for the importance of CUX1 in the development of pancreatic cancer, and highlight the importance of CUX1-dependent signaling pathways as potential therapeutic targets.

[Imminent fracture of the tibia due to an osteolytic lesion caused by an intraosseous tenosynovial giant cell tumor : An unusual clinico-histopathological constellation]. / Stabilitätsgefährdende Osteolyse der Tibia durch einen intraossären tenosynovialen Riesenzelltumor : Eine außergewöhnliche klinisch-histopathologische Konstellation.

The tenosynovial giant cell tumor is a rare disease of the joint mucosa, tendon sheaths and bursa. We report on the rare constellation of an intraosseous manifestation of the proximal tibia of a lower leg stump after Burgess amputation as a result of a locally uncontrollable tenosynovial giant cell tumor of the upper ankle. The curettage of the local findings and operative stabilization through an intramedullary composite osteosynthesis led to an early rehabilitation of the exoprosthesis care with regaining patient autonomy.

[Primary basal cell carcinoma of the caruncle]. / Primäres Basalzellkarzinom der Karunkel.

BACKGROUND: Primary basal cell carcinoma (BCC) of the caruncle is an extremely rare entity. Overall, only a few cases are described in the literature. With respect to the S2k guidelines on basal cell carcinoma of the skin, the eyelids, eyebrows and periorbital regions are regarded as zones with a high risk of recurrence. Due to its rarity hardly any data are available for primary BCC of the caruncle. METHODS: This article is based on a comprehensive literature review and a case presentation. RESULTS: In addition to a literature review this article reports the case of a 58-year-old male who presented at this department with a tumor of the caruncle. The histopathological examination revealed a BCC of the caruncle, which could be completely excised and showed no indications of recurrence in a follow-up period of 6 months. CONCLUSION: Primary BCC of the caruncle must be considered as a differential diagnosis in the case of unclear caruncular tumors. Moreover, the current data indicate an increased risk of recurrence.

Blistering and Skin Fragility Due to Imatinib Therapy: Loss of Laminin and Collagen IV as a Possible Cause of Cutaneous Basement Membrane Instability.

Imatinib mesylate (Glivec; Novartis AG, Basel, Switzerland) is a tyrosine kinase inhibitor which is used in the treatment of oncologic diseases like chronic myeloid leukemia and gastrointestinal stroma tumor (GIST). Among cutaneous side effects, bullous reactions are rare. The authors describe the case of a 66-year-old woman developing blistering and skin fragility on her hands, foot, lower legs, and back after intake of imatinib for treatment of GIST. Biopsy showed vacuolar alteration at the dermoepidermal junction (DEJ) associated with a few lymphocytes and a subepidermal blister. The upper papillary dermis below the vacuolar alteration and below the blister showed hyalinization and loss of elastic microfibrils. Direct immunofluorescence was negative for deposits of immunoglobulins. Immunofluorescence on cryosections revealed loss of laminin and collagen IV in vacuoles at the DEJ. Electron microscopy showed dissolution of lamina lucida and lamina densa of the basement membrane below as well as next to the vacuoles and blister. In conclusion, the authors present the first patient with GIST with blistering and skin fragility due to imatinib therapy. As a pathophysiological explanation the authors propose loss of laminin and collagen IV at the DEJ leading to basement membrane instability and blistering. This case also suggests additional features reminiscent of lichen sclerosus induced by imatinib, a drug which is actually known for its antifibrotic effects.

Intraepidermal Nerve Fiber Density: Diagnostic and Therapeutic Relevance in the Management of Chronic Pruritus: a Review.

In recent years, measurement of the intraepidermal nerve fiber (IENF) density has gained relevance in the diagnostics of chronic pruritus. This method allows the objectification and quantification of a small-fiber neuropathy, which may manifest clinically with pruritus, pain or dysesthetic sensory symptoms, such as burning, stinging and tingling sensations or numbness. Upon suspicion of a small-fiber neuropathy as a cause for chronic pruritus, targeted diagnostic procedures are essential for the early detection of the neuroanatomical changes. After a punch biopsy of the lower leg, the obtained tissue undergoes an immunofluorescence staining process with a primary antibody against the protein gene product 9.5. The IENFs can thus be detected and are quantified according to pre-determined guidelines based on an international consensus. In addition to morphological changes, functional impairment of small-fibers can be assessed using quantitative sensory testing by assessing detection and pain thresholds of various thermal and mechanic modalities. This method, however, is time-consuming and requires a specialized investigator, and thus it is not routinely used in the diagnostic investigation of chronic pruritus. Diagnosing a small-fiber neuropathy underlying chronic pruritus has therapeutic relevance. If possible, the underlying cause of the neuropathy should be treated. Alternatively, symptomatic therapy options include topical (capsaicin) and systemic (anticonvulsants and/or antidepressants) agents. Chronification processes may lead to refractory pruritus, and thus treatment should be initiated as soon as possible. The aim of this review is to present and discuss the measurement of the IENF density as a diagnostic tool and its role in the management of patients with chronic pruritus. A brief case report is presented to better illustrate the role of this diagnostic method in the clinical setting.