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.

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.

[Is it a sexually transmitted disease?] / Is dit een soa?

STD-associated questions and symptoms are submitted frequently to general practitioners and STD outpatient-clinics. In this teaching article we address 10 important clinical questions regarding epidemiology, risk assessment, testing policy, diagnostics and prevention. STD's form a separate category of infectious diseases because of the role of sexuality. Good communication about sexual behavior is indispensable for an adequate diagnosis. We discuss the recognition of extragenital manifestations of STD, which requires alertness. Estimating the STD-risk based on sexual behavior is essential for testing policy. Persons at high risk are tested for the big five. In other cases testing is based on symptoms and complaints. HIV and syphilis are serious std's. Early detection followed by treatment is important in preventing health damage and preventing further spread. Hiv-indicator-conditions are useful alarm-signs for this purpose. PrEP can help not to acquire hiv and increases sexual health. It can be prescribed by gp's and public health clinicians. But condom-use remains crucial in prevention.

[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.

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.

Acquired cutis laxa in childhood Sweet's syndrome.

In Sweet's syndrome, the essential features are the characteristic morphology of the lesions, their histologic appearance, the dramatic response to corticosteroids and the absence of scarring. We report an 8-month-old infant in whom Sweet's syndrome was diagnosed and who developed acquired cutis laxa in the skin lesions.

Clinical Presentation of Laboratory Confirmed Neurosyphilis in a Recent Cases Series.

OBJECTIVE: The worldwide increase in the incidence of syphilis necessitates alertness to the occurrence of neurosyphilis. Early recognition of neurosyphilis allows for timely treatment, leading to a better treatment outcome. This retrospective study aims to describe the clinical presentation of neurosyphilis in a recent series of neurosyphilis patients. METHOD: All patients were included with a new, laboratory confirmed, diagnosis of neurosyphilis in the period 2004-2018. The clinical data were analysed. RESULTS: 34 neurosyphilis patients (1 woman and 33 men) were identified. Age varied from 31-84 years (median age: 44 years). A history of syphilis infection was known for 11 (32%) patients; 12 (35%) patients were HIV seropositive. The distribution of the clinical syndromes was as follows: 16 patients with early neurosyphilis (acute meningitis, meningovasculitis and/or uveitis), 9 patients with late neurosyphilis (General Paralysis of the Insane and/or Tabes Dorsalis), 2 patients with symptoms of both early and late neurosyphilis, 6 patients with asymptomatic neurosyphilis and in 1 patient insufficient data were available to determine a clinical syndrome. Early neurosyphilis was seen in all age categories, late neurosyphilis only occurred in patients > 40 years. CONCLUSIONS: Neurosyphilis occurs in adults in all age groups, in men more frequent than in women, often in HIV-infected patients, and can present with a wide range of clinical syndromes. Usually no previous infection with syphilis is known.

To perfuse or not to perfuse? A retrospective comparative study to evaluate the effect of adjuvant isolated regional perfusion in patients with stage I extremity melanoma with a thickness of 1.5 mm or greater.

The use of isolated regional perfusion in an adjuvant setting for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 20 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (a region of West Germany bordering the Netherlands). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which tumor thickness was the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (P = .61), time to regional lymph node metastasis (P = .11), time to distant metastasis (P = .73), disease-free interval (P = .42), and survival (P = .90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups.

Alternating cycles of PVB and BEP in the treatment of patients with advanced seminoma.

33 patients (median age 39 years) with advanced seminoma were treated with 4 courses of alternating cisplatin-containing chemotherapy PVB/BEP (cisplatin, vinblastine and bleomycin; bleomycin, etoposide and cisplatin). Patients were classified as stage IIC (n = 7), IID (n = 9), III (n = 13) and IV (n = 4). 8 had had prior radiotherapy; 9 had an elevated beta human chorionic gonadotropin (beta HCG). 30 patients were evaluable for response and 33 for toxicity. During chemotherapy 3 patients died, 1 due to malignant disease, another due to a cardiac arrest, and 1 patient of a bleomycin pneumonitis. 13 (43%) had a complete remission and 17 (57%) had a clinical partial remission (residual radiographic mass). At a median follow-up of 28 months (range 16-88), 3 patients relapsed, 6-8 months after entry. After completion of therapy there were 2 deaths, 1 due to bleomycin pneumonitis and 1 neither tumour nor treatment related. 26 of 33 (79%) patients achieved a continuously disease-free status. Leucocytopenia and thrombocytopenia of WHO grade 3/4 occurred in, respectively, 32/33 (97%) and 20/33 (61%) of the patients. This study shows that alternating PVB/BEP in this group yields comparable response rates with non-alternating schedules but at the expense of considerable toxicity.

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.

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.

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.

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.

Isolated hindlimb perfusion in dogs: the effect of perfusion pressures on the oxygen supply (ptO2 histogram) to the skeletal muscle.

During regional isolated perfusion, neoplasms in extremities are treated with high doses of chemotherapeutic drugs by means of an extracorporeal circuit. The question is whether optimal tissue perfusion, which is essential for the therapy, is obtained by regulation of the extracorporeal circuit on an adequate perfusion flow or on an adequate perfusion pressure. To determine which perfusion pressure is needed to maintain adequate tissue perfusion, hindlimbs of six dogs were perfused at perfusion pressures 0, 15, 25, and 50 mm Hg below systemic mean arterial pressure. A multiwire polarographic oxygen electrode placed on the sartorius muscle permitted quantitative evaluation of tissue oxygenation by means of ptO2 histograms. Our results indicated that the perfusion pressure must be equal to or within 15 mm Hg below systemic mean arterial pressure to obtain optimal tissue perfusion. To maintain this perfusion pressure, high perfusion flows of about five to 10 times control femoral flows were needed. At a perfusion pressure 50 mm Hg below systemic mean arterial pressure, perfusion flow was normal, but tissue perfusion was severely impaired.

Isolated regional perfusion in the treatment of subungual melanoma.

Subungual melanoma is rare and represents only 1% to 3% of all diagnosed melanomas in Western countries. The tumor is frequently mistaken for a benign lesion and the delay in diagnosis and final treatment may be responsible for the high local recurrence rate and the low disease-free survival rate. From 1965 to 1982 the combined-modality therapy of amputation and adjuvant isolated regional perfusion with melphalan with or without dactinomycin was used in the treatment of 22 patients with subungual melanoma. Disease was staged according to the M. D. Anderson classification, as follows: stage I (primary melanoma), 11 patients; stage IIIA (in-transit metastases and/or satellitosis), three patients; stage IIIB (regional lymph nodes), seven patients; and stage IIIAB (in-transit metastases and/or satellitosis and regional lymph nodes), one patient. There were no cardiovascular complications and no treatment mortality. During a follow-up of at least 4.5 years, 12 patients (55%) developed distant metastases, including four patients with stage I disease (36%) and eight patients with stage III disease (73%). There were no locoregional recurrences. The median survival was three years (range, 0.5 to 12.5 years) and the overall five-year survival was 40%, with 56% of patients having stage I disease and 27% having stage III disease. The prognosis of subungual melanoma is determined by the stage of the disease. Isolated regional perfusion may prolong disease-free survival in patients with subungual melanoma compared with previously published data.

Groin dissection in the treatment of lower-extremity melanoma. Short-term and long-term morbidity.

Groin dissection was performed in 151 consecutive patients from 1970 to 1984. Groin dissections were therapeutic in 138 cases (91%) and elective in 13 (9%). One hundred forty-three patients (95%) underwent an ilioinguinal node dissection, while eight (5%) were treated with an inguinal node dissection. In 88 patients, the groin dissection was combined with isolated regional perfusion. Primary wound closure was performed in 140 patients (93%). There was no 30-day postoperative mortality. Complications included temporary seroma (26 [17%] of 151 patients), wound infection (14 patients [9%]), wound necrosis (five patients [3%]), and edema (30 patients [20%]). Residual inguinal node metastases after groin dissection did not occur. Morbidity of groin dissection did not increase when the groin dissection was combined with isolated regional perfusion. Quantification of the degree of edema in 66 patients revealed functional limitation due to edema in three patients (4.5%). This technique of groin dissection gives good results with minimal functional morbidity of the affected leg.

Thoracotomy as a staging procedure after chemotherapy in the treatment of Stage III nonseminomatous carcinoma of the testis.

Of 108 patients with a nonseminomatous testicular carcinoma, 28 with lung metastases were studied. After combination chemotherapy with cisplatin, vinblastine, and bleomycin (PVB), 11 patients underwent exploratory thoracotomy. Viable carcinomatous tissue, along with fibrosis, necrosis, and mature teratoma, was found in 4 patients. Three of these patients were successfully retreated with VP 16-213, cisplatin, and actinomycin D. In patients with residual pulmonary or mediastinal masses after chemotherapy, resection of the lesions is mandatory to demonstrate viable carcinoma so that treatment can be readministered. Thus, in our view, thoracotomy is a diagnostic procedure.

Late recurrence of mature teratoma in nonseminomatous testicular tumors after PVB chemotherapy and surgery.

We present the case histories of 3 patients in whom a growing mature teratoma developed twenty-eight, thirty-one, and thirty-three months after successful remission-induction chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB) for a disseminated nonseminomatous testicular tumor (NSTT). The serum tumor markers were not increased. The teratomas were all localized retroperitoneally, two being found near the site of excision of a residual tumor after remission-induction chemotherapy. Two of the 3 patients were alive without further treatment after excision of the teratoma; the third patient did not die of tumor progression, but mature teratoma was still present. Even if the serum tumor markers are not increased, recurrent tumors in patients previously given PVB chemotherapy because of a disseminated NSTT should be excised to establish their histology. En-bloc excision of the recurrent tumor is sufficient. It is pointed out that a mature teratoma can become a large cystic tumor in the course of time: the so-called growing mature teratoma syndrome. We believe that, after remission-induction chemotherapy of disseminated NSTT with a teratoma component in the primary testicular tumor, any residual tumor should be excised to prevent subsequent tumor progression.