The safe surgical margin in Ewing's sarcoma.

INTRODUCTION: There is recent evidence advocating the use of post-chemotherapy MRI for safe resection of primary bone sarcoma in providing a clear margin of disease. This paper challenges this view by providing evidence obtained from comparing surgical resection margin measurements calculated off the pre- and post-chemotherapy MRIs to the post-operative histological analysis. METHOD: A retrospective patho-radiological analysis of 10 patients treated for long bone Ewing's sarcoma. The pre- and post-chemotherapy MRI radiological measurements were correlated with the post-operative gross and microscopic histological specimens with the principle aim of determining which represented the accurate histological extent of disease and therefore which image set should be used in determining the surgical resection margins. RESULTS: In the 10 cases there was a discrepancy in the extent of pathological disease on comparative histological and radiological assessment. The mean age at presentation was 19.5years [4-45 years], with a female bias (n = 7/10). The lower limbs were more commonly involved than the upper limb (femur n = 2/10, tibia n = 3/10, fibula n = 2/10, humerus n = 2/10, ulna n = 1/10). There was no correlation between the percentage reduction in measured volume/length of pathological bone on sequential MRI and the percentage necrosis on histology. The average discrepancy between the length of pathological bone on histology and on MRI was 2.7 cm. Using the baseline pre-chemotherapy MRI to plan the surgical resection margins, 7/10 patients had their surgical resection margins through radiologically clear but pathologically abnormal bone (without histological evidence of residual tumour). Had the post-chemotherapy MRI been used a further 3 patients would have had their tumour resected through pathologically abnormal bone. No patients had or would have had tumour resected through residual tumour. CONCLUSIONS: The use of the post-chemotherapy MRI for planning surgical resection margins increases the risk of resecting through histologically abnormal bone that may have been previously contaminated by tumour, without significant benefit of preserving sufficient bone to facilitate joint or physeal sparing surgery. The evidence from this study supports current guidelines recommending the use of pre-chemotherapy MRI to plan safe surgical resection margins in Ewing's sarcoma.

Corrigendum to "Ectopic breast tissue presenting as an enlarging abdominal mass" [Radiology Case Reports 15 (2020) 733-740].

[This corrects the article DOI: 10.1016/j.radcr.2020.02.028.].

Myofibroblastic sarcoma of the base of tongue. Case report and review of the literature.

BACKGROUND: Mesenchymal malignancies with myofibroblastic differentiation exhibit a spectrum from low-grade myofibroblastic sarcoma mimicking fibromatosis to pleomorphic high-grade sarcoma. Low-grade myofibroblastic sarcoma shows a wide anatomic distribution with a predilection for the head-and-neck region; however, intermediate- and high-grade myofibroblastic sarcomas in this localization are exceptional. CASE REPORT: A 56-year-old woman with intermediate-grade myofibroblastic sarcoma of the base of tongue is presented. She was treated with surgical excision, but computed tomography proved local residual tumor. Reexcision and chemotherapy were refused by the patient. Irradiation was given to a total dose of 66 Gy. RESULT: 50 months after completion of radiotherapy, the patient is in good health without any evidence of disease. According to the review of the literature, base of tongue as the primary site of myofibroblastic sarcoma has not been published so far. CONCLUSION: Similarly to the low-grade form, intermediate- and high-grade myofibroblastic sarcomas may also occur in the head-and-neck region. In case of incomplete excision, radiotherapy may be an effective treatment.

[Long-term experience with multidisciplinary therapy of twenty-six patients with dermatofibrosarcoma protuberans]. / Dermatofibrosarcoma protuberans multidiszciplináris kezelésével szerzett hosszú távú eredmények 26 betegnél.

UNLABELLED: Dermatofibrosarcoma protuberans is a low or moderate grade malignant, uncommon soft tissue tumor. The tumor is characterized by slow, but locally aggressive growth, low metastatic potential and high recurrence rate. Initial treatment is the radical surgical excision, using traditional wide excision or Mohs surgery. In case of positive surgical margin or local recurrence, radio-chemotherapy and recently imatinib mesylate is used as adjuvant therapy. AIMS: Twenty-six patients treated multidisciplinary for dermatofibrosarcoma protuberans were followed up. METHODS AND RESULTS: Mean age of the patients was 44.7 years; mean follow-up time was 60.57 months. In fifteen cases (57.7%) R0 resection was performed, while eleven patients (42,3%) received only R1 resection. An average of 1.87 resections was necessary in order to achieve R0 resection. Six patients (23%) received adjuvant radiotherapy and two patients (7.6%) adjuvant chemotherapy following the removal of the primary tumor. Sixteen patients had no local recurrence. Ongoing treatments were needed in the case of ten patients (38.4%) who developed local recurrence. One patient has deceased due to distant metastases. Using statistical methods we examined the effects indicated as prognostic factors in the literature on local recurrence, precisely, the effect of age above 50 years and surgical radicalism. CONCLUSIONS: Dermatofibrosarcoma protuberans can be successfully treated with multidisciplinary therapy. A larger number of cases and randomized multicenter investigations are needed in order to reach more accurate conclusion.

[Long-term experience with therapy of a female patient with Gardner's syndrome, first presenting with extra-abdominal desmoid tumor, and review of the literature]. / Extraabdominalis desmoid tumorral megjeleno Gardner-syndromás beteg kezelésével szerzett hosszú távú tapasztalataink és irodalmi áttekintés.

Gardner's syndrome is a clinical subgroup of familial adenomatous polyposis, an autosomal dominant disease. It is characterized by gastrointestinal polyps and extra-intestinal manifestations including multiple osteomas, skin and soft tissue tumours. Aggressive desmoid tumours can be very difficult to manage in patients with Gardner's syndrome. We present a case of a 17-year-old female who presented with an aggressive desmoid tumor arising of the lumbar area as part of her Gardner's syndrome. She was treated with surgery, nonsteroidal anti-inflammatory drugs, tamoxifen and radiotherapy, and was followed up for 80 months. We conclude that desmoid tumors can precede gastrointestinal manifestations of familial adenomatous polyposis or Gardner's syndrome. Such patients should be evaluated with genetic testing followed by colonoscopy. Desmoid tumours should be managed in a multidisciplinary setting, as well.

[Diagnostic difficulties in serous "borderline" tumors of the ovary]. / A petefészek serosus "borderline" tumorainak diagnosztikai nehézségei.

About 15-20% of all ovarian neoplasms are of borderline type (or atypical proliferative or carcinoma of low malignant potential). They represent a common diagnostic and treatment problem both for the pathologist and for clinicians. The borderline tumors occur most commonly in childbearing age, show an indolent course and have good prognosis but are resistant to the traditional chemotherapies. The serous borderline tumors are the most common types of borderline ovarian tumors and they can cause differential diagnostic problems even for the experienced pathologist. We studied 30 cases which were diagnosed in our institute from 2000 to 2008. Thirteen were typical serous borderline tumors, in 7 cases the pattern was micropapillary, in 2 cases with microinvasion and in the remaining 8 cases the borderline tumors were associated with low-grade serous carcinomas. Seventeen of the 22 borderline cases were stage I tumors. There were noninvasive implants in the remaining 5 cases and in the cases of the low-grade carcinomas we could find, besides the noninvasive implants (in 3 cases), invasive implants or metastasis too. The main diagnostic problems in serous ovarian borderline tumors are the presence of micropapillary pattern, to detect microinvasion, or to differentiate the pseudo-borderline pattern of the low-grade serous tumors from a real borderline tumor and especially to diagnose the extraovarian diseases (types of implants). We discuss these diagnostic problems and criteria according to recent literature and our experience.

[Diagnostic problems of ovarian mucinous borderline tumors]. / A petefészek mucinosus "borderline" tumorainak szövettani diagnosztikai problémái.

About 15-20% of all ovarian epithelial neoplasms are of borderline type (or atypical proliferative or carcinoma of low malignant potential) and about 5-7% are mucinous type, which are the second most common type behind the serous borderline tumors. The borderline tumor is a serious diagnostic and treatment problem both for the pathologists and for clinicians. These tumors appeared to be intermediate in their histologic and prognostic features between the benign cystadenomas and clearly malignant carcinomas. The borderline tumors occur most commonly in childbearing age, and show an indolent course. Their prognosis is good, but they are resistant to the traditional chemotherapies. To diagnose the intraepithelial carcinoma, to detect the microinvasion and the expansive invasion in a mucinous borderline tumor, to differentiate from the metastasis of colorectal tumors may be very problematic in the majority of the cases. Eleven cases diagnosed as mucinous borderline ovarian tumor in our institute from 2000 to 2008 were reviewed. Eight out of 11 were intestinal type while three were cervical (mullerian) type. In 5 cases our diagnosis was intraepithelial carcinoma and in 5 cases we found microinvasion. We discuss all of these problems according to the latest literature and our experience, mentioning the problems of the peritoneal and ovarian pseudomyxomas.

The tip of the iceberg: lipomatous tumours presenting as abdominal or pelvic wall hernias.

Liposarcomas are the most common soft tissue sarcoma. They occur mainly in the thigh or retroperitoneum. Due to their size, lipomatous tumours can herniate either through the abdominal wall or in the groin. The part of the tumour that herniates represents only the 'tip of the iceberg', as the main part of the tumour is not detectable clinically and is often underestimated. Due to their deep location, lipomatous tumours are often large at the time of presentation and therefore their surgical management can be challenging. Furthermore, due to their delayed presentation, there is a higher risk of de-differentiation. In this pictorial review, we discuss different presentations of herniating lipomatous tumours according to the location of the abdominal wall defects. We aim to cover a wide spectrum of hernia defects including inguinal, ventral, lumbar, sciatic and ischiorectal hernias. We also present cases of tumours within the psoas compartment 'herniating' from the pelvis into the thigh. In case of a palpable lump, the first diagnostic step is to perform an ultrasound. If the herniating tissue is not fully accessible with ultrasound, additional cross-sectional imaging by CT or MRI is warranted. In this article, CT and MRI findings in lipomatous tumours are addressed and the use of contrast enhanced sequences in MRI is discussed. Patients' outcome depends not only on adequate diagnosis but also on the correct route of tissue sampling for histology and oncological resection to prevent local recurrence and loss of function. Therefore, referral to a specialised sarcoma treatment centre is key and needs to be done before biopsy.

Neuroendocrine Tumor Arising in a Tailgut Cyst: A Rare Presacral Tumor.

A tailgut cyst (retrorectal cystic hamartoma) is an uncommon lesion that develops in the presacral (retrorectal) space. Malignant change in a tailgut cyst is extremely rare and presents as a soft tissue (presacral) or bone (sacral) neoplasm. We report a case of tailgut cyst in which a neuroendocrine tumor developed in a 25-year-old female. Computed tomography and magnetic resonance imaging scans revealed a sacrococcygeal malformation with absent left S4 and S5 and a partly cystic lesion within the right presacral space. Histologically, the lesion contained cystic and solid elements. The cysts were lined by columnar and stratified squamous epithelial cells with underlying patchy smooth muscle. The solid element was a partly necrotic neuroendocrine tumor composed mainly of ribbons of tumor cells, which showed mitotic activity and expressed cytokeratin, chromogranin, and synaptophysin. Histologically, tailgut cysts are lined by epithelium and contain scattered smooth muscle bundles in the cyst wall. Although rare, the possibility of tailgut cyst with neuroendocrine tumor should be included in the differential diagnosis of an enlarging presacral tumor.

Subcutaneous calcification as a delayed complication of radiotherapy: a case report and review of the literature.

Subcutaneous calcification following radiotherapy is a very rare late complication. Here we report a case of radiotherapy for Hodgkin's disease in a patient with ichthyosis. Our review of the literature revealed that subcutaneous calcifications occurred in previously normal skin following irradiation. In our case the calcification developed in abnormal skin after telecobalt radiotherapy for mediastinal Hodgkin's disease. Ichthyosis is a systemic cutaneous disease and may increase the risk of late radiation complications.

The role of radiotherapy in the conservative treatment of ductal carcinoma in situ of the breast.

Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard of care for the treatment of early-stage (St. I-II) invasive breast carcinoma. However, controversy exists regarding the value of RT in the conservative treatment of ductal carcinoma in situ (DCIS). In this article we review the role of RT in the management of DCIS. Retrospective and prospective trials and meta-analyses published between 1975 and 2007 in the MEDLINE database, and recent issues of relevant journals/handbooks relating to DCIS, BCS and RT were searched for. In retrospective series (10,194 patients) the 10-year rate of local recurrence (LR) with and without RT was reported in the range of 9-28% and 22-54%, respectively. In four large randomised controlled trials (NSABP-B-17, EORTC-10853, UKCCCR, SweDCIS; 4,568 patients) 50 Gy whole-breast RT significantly decreased the 5-year LR rate from 16-22% (annual LR rate: 2.6-5.0%) to 7-10% (annual LR rate: 1.3-1.9%). In a recent meta-analysis of randomised trials the addition of RT to BCS resulted in a 60% risk reduction of both invasive and in situ recurrences. In a multicentre retrospective study, an additional dose of 10 Gy to the tumour bed yielded a further 55% risk reduction compared to RT without boost. To date, no subgroups have been reliably identified that do not benefit from RT after BCS. In the NSABP-B-24 trial, the addition of tamoxifen (TAM) to RT reduced ipsilateral (11.1% vs. 7.7%) and contralateral (4.9% vs. 2.3%) breast events significantly. In contrast, in the UKCCCR study, TAM produced no significant reduction in all breast events. Based on available evidence obtained from retrospective and prospective trials, all patients with DCIS have potential benefit from RT after BCS. Further prospective studies are warranted to identify subgroups of low-risk patients with DCIS for whom RT can be safely omitted. Until long-term results of ongoing studies on outcomes of patients treated with BCS alone (with or without TAM or aromatase inhibitors) are available, RT should be routinely recommended after BCS for all patients except those with contraindication.

[Reactivity of five different antibodies with benign and malignant melanocytic lesions]. / A különbözo antitestek reaktivitása benignus és malignus melanocitás daganatokban.

At the histological examination of an increasing number of melanocytic tumors there is a need to use various immunohistochemical methods. Currently, we are supplied by several antibodies working well on formalin-fixed, paraffin-embedded samples. We have tested five antibodies (S-100, HMB-45, Melan-A, MITF, PNL-2) on 34 benign and 34 malignant melanocytic tumors. We examined the specificity and sensitivity in the junctional and dermal component separately, with special consideration to features disturbing the evaluation (regression, halo-like inflammation, etc.). We have concluded that the histological diagnosis of melanocytic tumors is based on the detailed examination of traditional HE slides and the immunohistochemical methods only confirm or weaken our opinion.

[Combined surgery and radiotherapy in the treatment of ductal carcinoma in situ of the breast: preliminary results of the Hungarian multicenter prospective randomised study]. / In situ duktális emlokarcinóma kombinált sebészi- és sugárkezelése: a magyarországi multicentrikus prospektív.

The aim of this work is to report the preliminary results of the Hungarian multicentric randomised DCIS study. Between 2000 and 2007, 278 patients with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery were randomised according to predetermined risk groups. Low/intermediate-risk patients (n=29) were randomised to 50 Gy whole-breast irradiation (WBI) or observation. High-risk cases (n=235) were allocated to receive 50 Gy WBI vs. 50 Gy WBI plus 16 Gy tumour bed boost. Very high-risk patients (patients with involved surgical margins; n=14) were randomised to 50 Gy WBI plus 16 Gy tumour bed boost or reoperation (reexcision plus radiotherapy or mastectomy alone). Immunohistochemistry (IHC) was performed to detect the expression of potential molecular prognostic markers (ER, PR, Her2, p53, Bcl-2 and Ki-67). At a median follow-up of 36 months no recurrence was observed in the low/intermediate- and very high-risk patient groups. In the high-risk group, 4 (1.7%) local recurrences and 1 (0.4%) distant metastasis occurred. No patient died of breast cancer. In the high-risk group of patients, the 3- and 5-year probability of local recurrence was 1.1% and 3.1%, respectively. The positive immunostaining for Her2 (38%), p53 (37%) and Ki-67 (44%) correlated with a high nuclear grade. Significant inverse correlation was found between the expression of ER (77%), PR (67%), Bcl-2 (64%) and grade. Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1% in patients with DCIS. IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS.

Mycobacterium chelonae osteomyelitis presenting as a mycobacterial spindle cell pseudotumor.

We report a case of an 88-year-old man with osteomyelitis of the right ankle, with histopathology demonstrating a Mycobacterium spindle cell pseudotumor. The Mycobacterium contained in this spindle cell pseudotumor was Mycobacterium chelonae. M. chelonae spindle cell pseudotumors are rare and have only been reported twice previously in the literature. Similarly, M. chelonae presenting as the pathogen in bone infection is rare. Due to this unusual presentation of M. chelonae, the antibiotic rationale was based largely on case reports and consisted of imipenem, clarithromycin, and linezolid. Antibiotic complications were experienced by the patient. Despite a renally adjusted dose of imipenem, the patient experienced imipenem toxicity and his antibiotics were modified to tigecycline and clarithromycin. Although his symptoms were clinically resolving, the patient sadly passed away before completing treatment.

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing.

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer.

Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole-breast radiotherapy--4-year results of a randomized trial.

PURPOSE: To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. RESULTS: The 4-year actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p(WBI/HDR-BT) = 0.26; p(WBI/ELE) = 0.11; p(ELE/HDR-BT) = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. CONCLUSIONS: Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.

Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial.

PURPOSE: To report the 5-year results of a randomized study comparing the survival and cosmetic results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI). METHODS AND MATERIALS: Between 1998 and 2004, 258 selected patients with T1 N0-1mi, Grade 1-2, nonlobular breast cancer without presence of extensive intraductal component and resected with negative margins were randomized after breast-conserving surgery to receive 50 Gy/25 fractions WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy high-dose-rate (HDR) multicatheter brachytherapy (BT; n = 88) or 50 Gy/25 fractions electron beam (EB) irradiation (n = 40). RESULTS: At a median follow-up of 66 months, the 5-year actuarial rate of local recurrence was 4.7% and 3.4% in the PBI and WBI arms, respectively (p = 0.50). There was no significant difference in the 5-year probability of overall survival (94.6% vs. 91.8%), cancer-specific survival (98.3% vs. 96.0%), and disease-free survival (88.3% vs. 90.3%). The rate of excellent to good cosmetic result was 77.6% in the PBI group (81.2% after HDR BT; 70.0% after EB) and 62.9% in the control group (52.2% after telecobalt; 65.6% after 6-9-MV photons; p(WBI/PBI) = 0.009). CONCLUSIONS: Partial breast irradiation using interstitial HDR implants or EB to deliver radiation to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with carefully designed HDR multicatheter implants compared with the outcome after WBI.

[Histopathological prognostic factors of malignant melanoma]. / A melanoma malignum hisztopatológiai prognosztikus faktorai.

The incidence of melanocytic skin lesions, including malignant melanoma has increased in the past few years; histopathologists and dermatopathologists have to face them more often. The correct treatment of melanoma patients by the oncodermatologist and oncologist is based on the histopathological report containing the most important histological prognostic factors. However, the accurate interpretation of these factors may be difficult in the everyday practice, especially in reporting tumor thickness, the level of invasion, the type of exulceration and regression. It is important to standardize the content of the histopathological reports in a reproducible way.