Case report of a clinically indolent but morphologically high-grade cutaneous mast cell tumor in an adult: Atypical cutaneous mastocytoma or mast cell sarcoma?

We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow-up and still in complete remission.

[Skin-coloured vulvar papules]. / Huidkleurige vulvaire papels.

We report a 43-year-old woman with asymptomatic vulvar papules. Histopathology showed ducts with luminal differentiation and eosinophil debris with a tadpole shape. Based on these findings, the diagnosis vulvar syringoma was made. Syringoma are benign eccrine sweat gland tumour mostly located on lower eyelids and cheeks. Vulvar syringoma are rare.

Rush immunotherapy for wasp venom allergy seems safe and effective in patients with mastocytosis.

BACKGROUND: Patients with mastocytosis and wasp venom allergy (WA) may benefit from venom immunotherapy (VIT). However, fatal insect sting reactions have been described in mastocytosis patients despite previous immunotherapy. We investigated the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. OBJECTIVE: To investigate the safety and efficacy of (rush) VIT in patients with mastocytosis and WA. METHODS: We describe nine patients with cutaneous mastocytosis and WA who received VIT. Cutaneous mastocytosis was confirmed by histopathology and systemic mastocytosis was diagnosed according to World Health Organization criteria. VIT was given according to a rush protocol. Given the difference in safety and efficacy of VIT in patients with WA and honeybee venom allergy, we reviewed the literature for VIT with the focus on WA patients with mastocytosis and addressed the difference between patients with cutaneous versus systemic mastocytosis. RESULTS: Nine patients had WA and mastocytosis, of whom six had cutaneous mastocytosis, two combined cutaneous and systemic mastocytosis and one systemic mastocytosis. All patients received rush IT with wasp venom. Most patients had only mild local side effects, with no systemic side effects during the course of VIT. One patient had a systemic reaction upon injection on one occasion, during the updosing phase, with dyspnoea and hypotension, but responded well to treatment. Immunotherapy was continued after temporary dose adjustment without problems. Two patients with a previous anaphylactic reaction were re-stung, without any systemic effects. CONCLUSIONS: VIT is safe in cutaneous mastocytosis patients with WA, while caution has to be made in case of systemic mastocytosis. VIT was effective in the patients who were re-stung.

Narrowband ultraviolet B and medium-dose ultraviolet A1 are equally effective in the treatment of moderate to severe atopic dermatitis.

BACKGROUND: Phototherapy may be effective in atopic dermatitis (AD). Medium-dose (MD) ultraviolet (UV) A1 was introduced for the treatment of AD. Few immunohistochemical data are available pertaining to phototherapy in AD. Regulatory T cells may play a role in clearing AD. OBJECTIVES: We sought to compare the clinical and immunohistochemical effects of narrowband (NB) UVB and MD UVA1 treatment in patients with AD. METHODS: Thirteen adult patients with AD were included in this randomized investigator-blinded half-sided comparison study between NB UVB and MD UVA1. Disease activity was measured using the Leicester sign score. Skin biopsy specimens were taken before and after phototherapy. Regulatory T cells were stained with the forkhead box protein P3 (FoxP3). RESULTS: NB UVB and MD UVA1 both significantly decreased AD severity (P < .01) and the dermal cellular infiltrate. The percentage of FoxP3(+)CD3(+) T cells did not change after NB UVB or MD UVA1 treatment. LIMITATION: MD UVA1 therapy was given 3 times per week instead of the preferred regimen of 5 times per week. This was necessary to achieve good blinding of the study. CONCLUSIONS: NB UVB and MD UVA1 seem equally effective in the treatment of patients with moderate to severe AD. Neither MD UVA1 nor NB UVB had an effect on the percentage of FoxP3(+)CD3(+) T cells.

Modulation of the atopy patch test: tacrolimus 0.1% compared with triamcinolone acetonide 0.1%.

BACKGROUND: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis patients. We studied the effect of pretreatment with topical tacrolimus 0.1% on APT in nonlesional skin of patients with atopic dermatitis. METHODS: Nonlesional skin of the back of patients with atopic dermatitis (n = 8) was treated once daily for 3 weeks with tacrolimus 0.1% ointment. Cetomacrogol ointment (placebo) was used as a negative control and triamcinolone acetonide 0.1% ointment as positive control. Twenty-four hours after the last APT application, samples were taken from the three treated areas (t = 0 and 24 h) for immunohistochemical analysis. RESULTS: Pretreatment with tacrolimus ointment did not suppress nonlesional skin infiltrate, in contrast to triamcinolone acetonide. Furthermore, tacrolimus did not inhibit the induction of the APT macroscopically (t = 24 h). An equal influx of T cells, eosinophils, dendritic cells, CD64+ and Fc epsilon RI-positive cells was present compared with placebo. Only CD36+ and CD68-positive cells were inhibited compared with placebo. All cell types were significantly inhibited in triamcinolone acetonide-treated sites compared with placebo. CONCLUSIONS: Pretreatment with tacrolimus 0.1% ointment does not inhibit the APT reaction in patients with atopic dermatitis.

Cladribine therapy for systemic mastocytosis.

Patients with systemic mastocytosis (SM) can suffer from disabling symptoms related to mast cell mediator release or mast cell infiltration, requiring mast cell eradication. In the present absence of any curative therapy, a recent case report describing the efficacy of cladribine showed promising results. In a pilot study, the efficacy of cladribine (0.10-0.13 mg/kg in a 2-hour infusion, days 1-5; repeated at 4-8 weeks until 6 cycles) was studied. Ten patients with SM with severe symptoms were treated. Four patients were classified as having indolent or smoldering mastocytosis, 3 as having aggressive systemic mastocytosis, and 3 as having SM with an accompanying hematologic malignancy. Nine patients received 6 courses, 1 patient stopped because of toxicodermia. All responded concerning signs, symptoms, and mast cell parameters (serum tryptase and urinary histamine metabolite excretion), although none achieved a complete remission. Prolonged follow-up is required, as response is ongoing in most cases. One patient relapsed within 11 months and showed a second response. Side effects were mainly related to bone marrow suppression. Single-agent cladribine is an effective and relatively safe treatment for severe systemic mastocytosis. The optimal dose and schedule need to be explored.

Report of an international summer school--oncology for medical students--in 1996 in Groningen, The Netherlands.

An international summer school session, Oncology for Medical Students, was held in 1996 at Groningen University Hospital in The Netherlands. It was sponsored and organized by the WHO Collaborating Centre for Cancer Education-Groningen. The central focus of the two-week course was cancer in general health care. Various teaching techniques were used, but interaction between students and patients, and students and faculty, was considered a prerequisite. The approach was multidisciplinary, with a variety of clinical disciplines participating, including patient organizations and the Comprehensive Cancer Center North Netherlands. The students, from all over the world, presented posters about oncology topics in their countries. Evaluation showed that the course was highly appreciated by the students; in particular, the students felt they had benefitted from the multidisciplinary approach, the patient encounters, the psychosocial concern, the poster sessions, the quality of the teaching, and meeting other students from all over the world.

A retrospective comparative study evaluating the results of mild hyperthermic versus controlled normothermic perfusion for recurrent melanoma of the extremities.

The aim of this study was to investigate the role of mild hyperthermia (39-40 degrees C) in isolated cytostatic perfusion for patients with recurrent melanoma of the extremities. A total of 218 patients treated with mild hyperthermic perfusion was compared to 166 patients perfused under controlled normothermic conditions (37-38 degrees C). Only patients whose lesions had been excised before or at the moment of perfusion were eligible for this study. A variety of prognostic factors was controlled for in a Cox proportional hazards analysis. The application of mild hyperthermia did not influence limb recurrence-free interval nor survival (corrected P values 0.46 and 0.18, respectively). In this retrospective comparative study, no benefit for mild hyperthermia in regional isolated perfusion could be identified.

Functional morbidity of hyperthermic isolated regional perfusion of the extremities.

BACKGROUND: Isolated regional perfusion (IRP) of an extremity is a major operation. The therapeutic value for stage I melanoma is still controversial and is presently being investigated in a prospective, randomized study by the European Organization for Research and Treatment of Cancer. So far there are no reliable data available concerning the morbidity of IRP. Therefore, we performed a prospective, randomized study on this topic. METHODS: In a prospective study, a group of 97 patients with a stage I melanoma localized on an arm or leg were randomized for IRP with melphalan followed by wide excision (WE) and fasciotomy or for WE only. Morbidity was evaluated on the basis of the following parameters: duration of hospitalization, postoperative pain, postoperative performance, and grade of perfusion toxicity. At 12-month follow-up, a physical diagnostic examination was performed to measure the mobility of the joints, and the circumference and volume of the treated and untreated extremities. RESULTS: All the parameters, including the physical diagnostic examination, could be evaluated in 83 of the 97 patients (8 patients died of metastatic disease and 1 patient died of another disease before they could be investigated; 2 patients were in too poor physical condition due to metastases to be examined, and 3 patients were unable to participate for nonmedical reasons). Age and sex distribution were comparable in the various patient groups. Treatment mortality was 0%. There were no complications except for urine retention (one patient) and wound dehiscence (one patient). After IRP + WE of the lower limb, the period of hospitalization was an average of 1.9 days longer (p = 0.01) than for WE on the limb only. This difference was absent for the arm. Naturally after perfusion, there was a significant difference in toxic reactions (edema and pain) between the IRP + WE patients and the WE-only patients. However, at 12-month follow-up, the difference in morbidity between IRP + WE and WE-only patients was no longer present: Morbidity of joints and circumference of the limb were the same. A number of subjective complaints were encountered fairly often after IRP + WE (e.g., pricking sensations or pain during changes in the weather), which can possibly be explained by fibrosis caused by perfusion. These complaints were not quantified further because they did not hinder the patients' functioning. CONCLUSIONS: In a long term, IRP with fasciotomy does not cause any additional morbidity. Immediately after the operation, there was more morbidity as a result of the perfusion, which caused a 2-day-longer period of hospitalization in the patients with lower-limb perfusion compared with those who underwent WE only. These findings are in contrast to those in the literature, in which 25% limitation of motion in the ankle joint after perfusion is mentioned. One explanation may be that we always performed fasciotomy after perfusion to prevent (sub)clinical compression syndrome and avoid late fibrosis.

Development and test of an extendable endoprosthesis for bone reconstruction in the leg.

A malignant bone tumour may develop in the femur of a child. In the majority of cases it will be necessary to resect the bone involved, growth plate and adjacent tissues. A modular endoprosthetic system has been developed which can be extended non-invasively to bridge the defect resulting from such a resection. Elongation is achieved by using an external magnetic field. In vitro tests with a prototype showed that the lengthening element met all requirements. Six animal experiments showed that the lengthening element also functioned in vivo.

Positron emission tomography with fluorine-18-fluorodeoxyglucose for the evaluation of therapeutic isolated regional limb perfusion in a patient with soft-tissue sarcoma.

METHODS: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. RESULTS: PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. CONCLUSION: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

The clinical staging of rectal cancer in patients treated by preoperative radiotherapy.

We describe the results of clinical and (or) surgical staging used by the same surgeon to select a group of 41 patients with advanced rectal cancer for preoperative radiotherapy. Fifteen patients with resectable but advanced rectal cancer were subjected to a short course of radiotherapy (30 Gy in 10 days), immediately followed by resection. High dose preoperative radiotherapy (50-56 Gy in 5 weeks) was administered to 26 patients with borderline resectable or fixed cancer. Adequate resection of the tumour was possible in 21 of these 26 patients 4 weeks after the end of the radiotherapy. A total of 36 patients thus underwent resection after preoperative radiotherapy. No radiotherapy related acute or late morbidity was seen. On 31 December 1992 the results were investigated retrospectively. The median time since entering into the study was 87 months (range 27-141). During the follow-up, pelvic recurrence was detected in six patients; one patient had concomitant distant metastases. The local recurrence free survival at 5 years calculated by the Kaplan-Meier method was 72% (95% CI 58-85). Distant metastases without local recurrence developed in 11 patients. The calculated survival at 5 years was 45% (95% CI 30.5-59).

Intraoperative irradiation of the canine pancreas: short-term effects.

Intraoperative electron beam radiotherapy (IORT) is clinically used as a potential adjunctive treatment to surgery of locally advanced pancreatic and gastric cancer. The tolerance of the pancreas to IORT was studied in 15 adult beagles, divided in 3 groups of 5 beagles in which 25, 30 or 35 Gy IORT was delivered through a 6-7 cm circular lucite cone with 6-8 MeV electrons to the pancreas and medial wall of the duodenum. The dogs were followed for endocrine and exocrine pancreatic insufficiency. Two dogs (13%) developed radiation-induced morbidity which consisted of a common bile duct stenosis and an enterocolic fistula, as was confirmed at autopsy after 8 and 18 months, respectively. After a follow-up of 1 year, none of the dogs had developed pancreatitis, diabetes or exocrine insufficiency. There was a significant reduction in serum insulin levels and glucose clearance rates without overt diabetes for 30 Gy and 35 Gy (p < 0.05). No significant changes were found for 25 Gy. This study suggests that 25 Gy IORT to the pancreas may be used clinically, and that higher IORT doses may induce endocrine pancreatic insufficiency in the long-term.

Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT).

PURPOSE: The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. METHODS AND MATERIALS: The feasibility of delivering single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. RESULTS: There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. CONCLUSION: This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated.

Total pelvic exenteration: a justified procedure.

Twenty patients with advanced primary or locally recurrent pelvic tumours treated by total pelvic exenteration are described. There wer no operative or postoperative deaths. The most frequent postoperative complications appeared to be related to previous irradiation. Four patients developed non-fatal intestinal complications within 30 days of operation that required further surgery. After a mean follow-up of 19 months the crude 2-year survival rate was 40 per cent. This procedure is judged to be useful in a selected group of patients.

The interscapulothoracic amputation in the treatment of malignant diseases of the upper extremity with a review of the literature.

The majority of patients with soft tissue sarcoma (STS) or bone sarcomas (BS) of the upper limb can be treated today with limb saving procedures using combined modality therapies. However, for a small group of patients the interscapulothoracic (IST) amputation is the only final surgical treatment with either a curative or a palliative intent. Since 1972, 12 patients seven males and five females, median age 36 years (range 13-82) underwent an interscapulothoracic amputation; five for bone sarcomas, five for soft tissue sarcoma and two for locoregional metastases. There was no post-operative mortality or morbidity. During a median follow-up of 8 years (range 0.25-15), there was no local recurrence. The five-year survival rate for the soft tissue sarcomas was 80% and for the bone sarcomas 30%. The interscapulothoracic amputation is one of the major ablative surgical procedures which should be performed with curative intent, very rarely with a low palliative intent. The prognosis of an interscapulothoracic amputation for shoulder girdle malignancies is not different from extremity soft tissue sarcomas or bone sarcomas located more distally. The morbidity and local recurrence rate after interscapulothoracic amputation should be negligible.

Posterolateral neck dissection: technique and results.

Posterolateral neck dissection, alone or combined with a modified radical neck dissection, may be an appropriate method of treating occult and clinically manifest nodal metastases of malignant epithelial tumours of the skin of the posterior scalp. The technique and results are described in 21 patients treated between February 1981 and November 1989. Transformation of nodal status from cN0 to pN+ was seen in five of 13 patients treated electively, who may benefit from such a procedure. During a mean follow-up of 47 months the disease was controlled locally in all patients. Three patients suffered regional recurrence of whom only one had a nodal recurrence within the region previously operated on. The results of this limited retrospective study confirm the value of posterolateral neck dissection in posterior scalp lesions.