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A letter to the editor is presented in response to the article "Angiolymphoid Hyperplasia With Eosinophilia in Pregnancy" in the September 2005 issue.

Background: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting., Methods: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated., Results: Twenty-five patients were included with a median age of 78 (65-82) years. The median treatment duration was 48 (16-72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%., Conclusions: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.

Langerhans cell histiocytosis (LCH) is characterized by mutations of the RAS-RAF-MAPK signaling pathway. We analyzed MAP2K1, NRAS and KIT mutation incidence in skin lesions of BRAF wild-type (wt) LCH patients. We evaluated the occurrence of MAP2K1, NRAS and KIT mutations in seven LCH and one indeterminate cell histiocytosis (ICH) patients. MAP2K1 mutation frequency was found to be 3/7 (42.9%) in LCH and also found in ICH. Similarly, the KIT mutation frequency was found to be equally prevalent (4/7, 57.1%) in LCH and also occurred in ICH. Involvement of KIT exons in LCH-ICH indicated that exon 9/11/18 were equally prevalent followed by exon 13. This exploratory analysis on BRAF-wt LCH revealed a KIT mutation rate comparable to MAP2K1. Although the detected KIT mutations are different from activating mutations found in other KIT-dependent neoplasms, our data suggest that KIT-inhibitors might have a role in treating BRAF-wt LCH patients.

Dear Editor, Lymphomatoid papulosis (LP) is a chronic, recurrent, usually self-limited papulonecrotic or papulonodular skin disease, which belongs to the group of primary cutaneous CD30+ lymphoproliferative disorders (1). Three main histological subtypes of LP have been recognized: type A (histiocytic), type B (mycosis fungoides-like), and type C (anaplastic large cell lymphoma-like). Recently, new histologic LP variants classified as type D (CD8-positive, cytotoxic form) and type E (angioinvasive form) have also been described. The etiology of LP has not been determined to date (2-4). Herein we report a case of LP type B evolving in a patient with Crohn's disease after treatment with infliximab and adalimumab. A 38-year-old man suffering from terminal ileitis form of luminar Crohn's disease for 10 years presented at our department. During the last 10 years, the patient had been treated with a number of conventional disease-modifying anti-inflammatory drugs including non-steroid anti-inflammatory drugs, mesalazine, and immunomodulatory agents such as corticosteroids and azathioprine. As the disease was not sufficiently controlled, TNF-α inhibitor therapy was initiated. Infliximab was administered in standard dosage (5 mg/kg body weight every 8 weeks after the induction period) for one year. Concomitant therapy with azathioprine was established to reduce the risk of adverse immunological reactions. Since the patient showed only partial clinical response, infliximab was switched to adalimumab (40 mg biweekly), resulting in notable improvement. 18 months after the initiation of adalimumab treatment, asymptomatic, small, red to brown papules developed on the extremities. Multiple lesions were observed, initially on the legs, but the symptoms rapidly progressed to the arms and trunk (Figure 1). An acquired ichthyosis further complicated the disease course by extended, extremely xerotic, scaling skin lesions. Neither systemic symptoms nor significant lymphadenopathy was observed. The clinical picture suggested either ichthyosiform mycosis fungoides or a coincidence of LP and acquired ichthyosis. The histology of a typical papule showed perivascular and periadnexal lymphoid infiltration with massive hemorrhage in the dermis. The infiltration was dense, composed of small-to-medium-sized lymphoid cells showing focal significant epidermotropism (Figure 2). Most observed epidermal lymphocytes were CD3+, CD4+, and CD30+, while the dermal infiltration had higher CD4 and lower CD30 expression (10-15%). Polymerase chain reaction (PCR) analysis of skin and peripheral blood samples did not show clonal rearrangement of T-cell receptor gamma (TcRgamma) genes. Normal phenotypes of lymphocyte subsets were detected by flow cytometry of peripheral blood. Ichthyosiform mycosis fungoides was excluded since histology of ichthyosiform skin lesions showed only hyperkeratosis with a reduced granular layer. While the cutaneous CD4+ epidermotropic infiltrate was suspicious of either mycosis fungoides or LP type B, the complexity of clinicopathological data confirmed the diagnosis of LP type B. The peripheral blood counts, serum biochemical tests, and urinalysis were within normal range, while the elevated serum anti-Saccharomyces cerevisiae antibodies (ASCA) of IgG and IgA subclasses indicated the activity of Crohn's disease. Adalimumab and azathioprine were discontinued, and oral budesonide therapy was started in combination with topical corticosteroids and PUVA phototherapy. The skin lesions resolved with hyperpigmentation, and there was no relapse during the twelve-month follow-up. Recent data suggest that LP occurs more commonly in immunocompromised patients, especially in those with solid organ or bone marrow transplants (3). Though TNF-α inhibitors have dramatically advanced the treatment of various diseases, the risk of lymphoma associated with their use remains controversial (5). Several cases of cutaneous lymphoproliferative disorders associated with TNF-α inhibitor treatment have been reported, including two patients with LP (6). One of the two patients with LP received infliximab for Crohn's disease (7), while the other one had juvenile rheumatoid arthritis and received adalimumab (8). Our case is the third report on LP developing under TNF-α inhibitor therapy and the first LP type B in a patient with Crohn's disease treated with infliximab and later with adalimumab. A further interesting aspect of our case is that it also represents an example of the known association of acquired ichthyosis with inflammatory bowel disease (9). Multidisciplinary management was needed to provide optimal care and disease outcome for our patient. Since it is usually difficult to prove causality in most of such cases, it is important to collect similar clinical observations. Acknowledgments: The authors are grateful to Dr. László Bene, Dr. József Szakonyi, and Dr. Fruzsina Kovács for additional medical care of the patient and to Tamás Szaák for the clinical photos. The authors thank Prof. Miklós Sárdy for his critical review of the paper.

Ehlers-Danlos syndrome (EDS) is the name for a heterogenous group of rare genetic connective tissue disorders with an overall incidence of 1 in 5000. The histological characteristics of EDS have been previously described in detail in the late 1970s and early 1980s. Since that time, the classification of EDS has undergone significant changes, yet the description of the histological features of collagen morphology in different EDS subtypes has endured the test of time. Nonlinear microscopy techniques can be utilized for non-invasive in vivo label-free imaging of the skin. Among these techniques, two-photon absorption fluorescence (TPF) microscopy can visualize endogenous fluorophores, such as elastin, while the morphology of collagen fibers can be assessed by second-harmonic generation (SHG) microscopy. In our present work, we performed TPF and SHG microscopy imaging on ex vivo skin samples of one patient with classical EDS and two patients with vascular EDS and two healthy controls. We detected irregular, loosely dispersed collagen fibers in a non-parallel arrangement in the dermis of the EDS patients, while as expected, there was no noticeable impairment in the elastin content. Based on further studies on a larger number of patients, in vivo nonlinear microscopic imaging could be utilized for the assessment of the skin status of EDS patients in the future.

Lymphomatoid papulosis (LyP) belongs to CD30+ lymphoproliferative disorders with indolent clinical course. Classic histological subtypes, A, B and C are characterized by the CD4+ phenotype, while CD8+ variants, most commonly classified as type D, were reported in recent years. We present 14 cases of CD8+ LyP. In all patients, self-resolving or treatment-sensitive papules were observed. Of 14 cases 7 produced results with typical microscopic features of LyP type D mimicking primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma. The infiltration pattern in 4 of 14 cases were consistent with classic LyP type B, without CD30 expression in two cases, resembling mycosis fungoides (MF). The morphology of 2 of 14 cases shared a certain consistency with classic type A and C, lacking eosinophils and neutrophils. Extensive folliculotropism characteristic to type F was observed in 1 of 14 case. Significant MUM1 and PD1 expression were detected in 2 of 14 and 3 of 14 cases, respectively. We concluded that CD8+ LyP may present with different histopathological features compared with type D, similar to CD4+ LyP variants. Differential diagnoses include CD8+ papular MF, folliculotropic MF and anaplastic large cell lymphoma in addition to primary cutaneous aggressive epidermotropic T-cell lymphoma. We emphasise that rare CD8+ LyP cases may exist with CD30-negativity., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pregnancy associated melanoma (PAM) by definition appears during pregnancy or within 1 year after delivery. In this retrospective study we analysed the pathological characteristics and survival rate of PAM and matched the data with non-pregnant age- and stage-matched control patients. Between 2003 and 2014, 34 pregnant women (aged 32.5 ± 5.6 years) were diagnosed with melanoma at the Department of Dermatology, Venereology and Dermatooncology of the Semmelweis University. During the pathological process histologic subtype, Breslow thickness and Clark level, tumor cell type, mitotic rate, peritumoral inflammation, as well as ulceration, regression, necrosis, vascular invasion and presence of satellite were analyzed and related to clinical data. Primary tumor location and clinical staging, disease course, local recurrence and metastases, 5-year survival rate, other tumor development before or after the diagnosis of melanoma have also been documented. We found no difference in all parameters between pregnant and non-pregnant melanoma cases except peritumoral inflammation which was higher in PAM group, moreover the presence of mild inflammation was significantly higher in PAM group compared to non-pregnancy associated melanoma (NPAM) women group.

Mycosis fungoides (MF) is a common, indolent primary cutaneous T-cell lymphoma (CTCL), with rare, more aggressive variants, such as folliculotropic MF (FMF). A minority of the MF cases may undergo large cell transformation (T-MF) associated with poor prognosis. A selection of microRNAs (miRs) contribute to the pathogenesis and progression of classic MF, and may also be useful in differential diagnostics. However, the molecular background of FMF and the mechanisms involved in large cell transformation are obscure. We analyzed the expression of 11 miRs in 9 FMF and 7 T-MF cases. Three miRs, including miR-93-5p, miR-181a and miR-34a were significantly upregulated in both FMF and T-MF. FMF also showed overexpression of miR-155 and miR-223, while miR-181b and miR-326 were overexpressed in T-MF cases compared to controls. These results by identifying a number of differentially expressed microRNAs add further insight into the molecular pathogenesis of folliculotropic MF and large cell transformation of MF.

Incidence of subsequent malignant tumor development in 740 patients with primary cutaneous melanoma verified between 2006 and 2010 at the Semmelweis University was studied retrospectively and was compared to data of sex and age matched Hungarian population. The follow-up period was 1499 person-years for the whole group from the diagnosis of index melanoma with an average of 2 years. Standardized incidence rate (SIR) was established as the ratio of observed and expected values. The risk of all subsequent malignancies was 15- and 10-fold higher in males (SIR: 15.42) and in females (SIR: 10.55) with melanoma, than in the general population. The increased cancer risk resulted mainly from the significantly higher skin tumor development: SIR values were 160.39 and 92.64 for additional invasive melanoma and 342.28 and 77.04 for subsequent in situ melanoma in males and females, respectively. Non-melanoma skin cancers also notably contributed to the higher risk, the SIR was elevated in both genders to the same extent (males: 17.12, females: 17.55). The risk was also significantly higher for extracutaneous tumor development like chronic lymphocytic leukemia, colon and kidney cancer (both genders), non-Hodgkin's lymphoma, cervical cancer (females), and bladder carcinoma (males). These data underline the importance of patient education and the necessity of frequent medical follow up, including a close-up dermatological screening of melanoma survivors for further malignancies.

Introduction: Mastocytosis is a clonal mast cell proliferative disease, divided into cutaneous and systemic forms. The characteristic symptoms are caused by neoplastic mast cell infiltrations in different organs and/or the release of mediators., Aim: The aim of the authors was to summarize their clinical observations in patients with mastocytosis., Method: 22 adult patients diagnosed consecutively with mastocytosis were enrolled in the study. Skin and bone marrow biopsies were taken to establish the diagnosis and perform c-KIT mutation (D816V) analysis., Results: One of the 22 patients had teleangiectasia macularis eruptiva perstans, while 20/22 patients had urticaria pigmentosa. All patients had cutaneous lesions. In 12 patients iliac crest biopsy was performed and 9 of them had bone marrow involvement, classified as indolent systemic mastocytosis. The c-kit mutation D816V was found in one subject both in skin and bone marrow samples. The patients were treated with antihistamine, PUVA, interferon-α or imatinib., Conclusions: The authors draw attention to this rare disease in order to help recognition of relevant signs and symptoms and establish an early diagnosis.

Introduction: Survival of patients with malignant melanoma primarily depends on tumor stage. Hungarian National Cancer Registry does not specify tumors according to TNM stages., Aim: The authors aimed to survey the stage distribution of melanomas at the Department of Dermatology, Dermatooncology and Venerology, Semmelweis University., Method: 1160 patients (558 males and 602 females, aged 60.5±16 and 57±17 years, respectively) diagnosed with cutaneous melanoma between 2004-2009 were included., Results: In comparison with international studies, the case distribution was favorable in stages IA and IV, i.e. the proportion of early melanomas was relatively high (IA: 43.8%), while the incidence in stage IV was low (0.4%). In stages IB-IIA the incidence was significantly lower, while in IIC, IIIA, IIIB it was higher as compared to published data from Western-Europe, Australia and the United States., Conclusions: The study underlines the necessity of prevention and awareness campaigns that may result in increase of early diagnosis of melanomas.

Pathological classification of malignant melanoma did not change in the past decade, it was just completed with UV-induced skin alterations. A new feature, however, is the establishment of molecular classification of melanoma indicating that beside the most frequent genetic alterations (BRAF, NRAS, CKIT mutations) there is a wide variety of rare molecular subclasses. Unfortunately, none of these genetic alterations can be used to discriminate benign lesions from malignant ones. The frequently used "melanoma" markers are mostly melanosomal markers, therefore they are not helpful for this diagnostic purpose either. More recently, novel FISH kits have been developed analyzing characteristic copy number alterations specific for malignant melanoma. Though melanosomal markers are helpful in differencial diagnostics, the presence of normal melanocytes in various tissues (lymph nodes, intestine or brain) requires application of molecular techniques when melanoma metastasis is in question.

The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.

A 49 year-old man presented to our clinic. He had a history of lymphomatoid papulosis since childhood. At age 44, regional lymph node manifestation of anaplastic lymphoma kinase (ALK) anaplastic large cell lymphoma (ALCL) developed. Chemotherapy resulted in complete remission of the lymphadenopathy. Four years later, systemic relapse was detected which was refractory to therapy. Histology and immunohistochemistry showed congruent characteristics of multiple skin and lymph node biopsies: diffuse mixed infiltrate with large, anaplastic CD30 cells. Immunophenotype and microscopic morphology suggested a common origin of the different manifestations-however, this could not be proven due to lack of T-cell receptor (TCR) gamma gene rearrangement in most of the samples. The diagnosis of ALK-negative systemic ALCL with cutaneous symptoms was set up at the second flare up, however, the possibility of primary cutaneous ALCL was not excluded steadily. Lymphomatoid papulosis, primary cutaneous ALCL, and systemic ALK ALCL are 3 different entities but the separation of them cannot be solved without distinctive diagnostic tools.

The subcutaneous infiltration of liquid paraffin is still used for penile enlargement. The procedure has many complications. A late problem is the development of foreign body granulomas known as paraffinomnas. They may be necrotic and ulcerated, requiring acute, radical surgical excision.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK-cell lymphoma, is an uncommon, aggressive non-Hodgkin's lymphoma with cutaneous, lymph node, and bone marrow involvement at presentation. The disease is characterized by early leukemic phase; however, central nervous system involvement is rarely reported. Herein we describe two cases of CD4+/CD56+ hematodermic neoplasm with meningeal manifestation. Microscopic analysis and flow cytometry of cerebrospinal fluid proved to be diagnostic; however, imaging studies were not informative. These observations call attention to the possibility of central nervous system involvement, which could be more common than expected previously. Authors recommend routine cerebrospinal fluid analysis and prophylactic intrathecal chemotherapy in patients with this highly aggressive disease.

Intravascular lymphoma is an uncommon, very aggressive extranodal non-Hodgkin lymphoma that most frequently involves the skin and central nervous system. Most cases are of B-cell origin; T-cell phenotype is extremely rare. Malignant cells proliferate within the lumens of capillaries, arterioles, venules, and small arteries; vascular occlusion is responsible for the clinical signs and symptoms. The prognosis of this high-grade B-cell lymphoma has improved since the introduction of the anti-CD20 monoclonal antibody, rituximab. We describe a case of B-cell intravascular lymphoma successfully treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisolone.

The 54 year-old vegetarian patient has taken oral colloidal silver for two years to stimulate his immune system. The silver intake resulted in diffuse grayish discoloration on the face. His laboratory values were in the normal range, and no internal organ disease was detected. The histology of the forehead skin confirmed the diagnosis of argyria. Argyria is a condition associated with chronic local or systemic exposure to silver-containing products. The silver is typically deposited in skin, fingernails, oral mucosa and conjunctival membranes. There is no effective treatment for this condition. With the availability of pharmacologic alternatives, physician-directed use of silver-containing products had significantly declined. We review the literature and call attention to the adverse effects and dangers of the widely used paramedicinal colloidal silver products.

A 51-year-old female developed urticarial lesions of her right forearm which progressed into transient edema and subcutaneous swelling. Later a small infiltrated subcutaneous nodule also appeared and was removed in toto. Histopathological examination revealed the presence of Dirofilaria repens. This worm is the cause of an endemic zoonosis in the Mediterranean area. In the past decade many cases have been reported worldwide, but the condition appears rare in Hungary and skin findings have not been described.

The authors' report a case of a 26-year-old female. In 1996, and 1997 she underwent cosmetic lip augmentations (polymethyl methacrylate and silicone). After a six-year symptom free period sudden swelling of the lips developed and red-brown papules and subcutaneous nodules appeared in the scars of various body parts ( permanent make-up, tattoos, umbilical piercing). The clinical features, radiological signs and histology proved the diagnosis of systemic sarcoidosis. Systemic corticosteroid treatment was introduced. After 4 months of treatment the pulmonary and clinical symptoms showed regression. To be able to suspend the systemic treatment the silicone implant was removed.

A 59-year-old male patient developed a necrotizing ulceration on the right shin. Both clinical and histopathologic examinations suggested pyoderma gangrenosum. After temporary improvement of skin symptoms under peroral glucocorticoid treatment, a hemorrhagic-purulent discharge started from the nose, he began to have fever, malaise, cough, and a chest X-ray revealed inflammation in the lung. Cerebral CT and MRI disclosed midline bone loss within the nasal septum and granulomatosus tissue masses protruding into the right orbit. The c-ANCA test was positive, serum IgA was elevated, and he had microhaematuria and proteinuria. In this severe case of Wegener's granulomatosis prolonged methylprednisone and cyclophosphamide treatment was initiated. Both the skin symptoms and the granulomatosus infiltrations resolved.

14 patients suffering from early stage mycosis fungoides were treated with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4 patients in stage II a and 6 patients in stage II b/during 3-21 months time course. Interferon alpha 2-a was administered 3 times a week, in escalating dose from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the patients responded well to the treatment. Partial remission was observed after 4-13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9 months of the treatment. Side effects occurred frequently: weight loss, pain, fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the side effects the dose of the interferon was reduced individually, the dose reduction did not cause relapse.

The authors are discussing hepatic and extrahepatic pathologic processes caused by hepatitis C virus (HCV) infection and they focus their interest to the skin disorders appearing in the presence of chronic, active HCV infections. The trigger of the immunologic processes leading to dermatologic manifestations are the activated T cells (CD8 + cytotoxic T lymphocytes), cytokins, and also the expansion of certain B cells. Pathologic immunologic phenomena may initiate various dermatologic manifestations. Immunoglobulins, immuncomplexes generated by the disease itself are manifested as various forms of cutan vasculitis. In the present series of patients (pts), HCV related skin disorders known from the literature were diagnosed in eleven cases and they were representing 7 different disease entities. These were palpable purpura (3 pts), urticaria, prurigo and alopecia areata (2-2 pts), lichen ruber planus, pruritus and vitiligo (1-1 patient respectively). The case reports of 2 pts, one with palpable purpura (vasculitis purpurica), one with prurigo and vitiligo are presented in details.

The primary cutaneous CD30 positive large cell lymphoma is a rare tumor, confined to the skin. The characteristic clinical picture is a large, often exulcerating sometimes spontan regressing tumor or nodule. Dense infiltration of large, anaplastic or non-anaplastic T or non T, non B cell of the dermis is characteristic. Generalization, lymph node or internal manifestation is rare, the prognosis is favourable. A 25-year-old male patient is presented, in whom generalised skin symptoms-itching, reddish-brownish papules with central necrosis developed. Two years later general symptoms-fever, fatigue, lymph node and spleen enlargement, increased in white blood cell count with prominent eosinophilia, increase in CD4 number occurred. The histology and immunohistology of the skin and peripheral lymph node showed large, anaplastic, CD30 positive T cell infiltration. CHOP, then BACOP treatment resulted in regression of the skin and the internal symptoms.

Actinic granuloma is a rare condition. Its acceptance as a defined disease has been queried several times. The authors observed a classic case in a patient with alcoholic cirrhosis of the liver and diabetes. The possible role of metabolic disturbances in the pathogenesis of this syndrome is reviewed.

30 rats were divided into 3 experimental groups. These included 8 days of Lipofundin treatment + 8 days recovery period (Group I), 16 days of Lipofundin treatment (Group II), and 16 days of Lipofundin treatment + 8 days recovery period (Group III). After sacrifice semi-thin and ultra-thin sections prepared from the aorta segments were examined light and electron microscopically. In addition to the development of alterations characteristic of the Lipofundin-model, the accumulation of collagen fibres was also observed. After 16 days of Lipofundin treatment the alterations were much more advanced than after 8-day treatment. Subsequent migration of smooth muscle cells through the newly formed internal elastic lamina was apparent and led to thickening of the sclerotic plaque. When the 16-day Lipofundin treatment was followed by a recovery period of 8 days prior to sacrifice, no signs of regression were seen. The alterations were present in unchanged form and the only difference was in the extent of accumulation of collagen fibres.