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Lindsey Oudijk,
José Gaal,
Esther Korpershoek,
Francien H van Nederveen,
Lorna Kelly,
Gaia Schiavon,
Jaap Verweij,
Ron H J Mathijssen, Michael A den Bakker,
Rogier A Oldenburg,
Rosa L E van Loon,
Maureen J O'Sullivan,
Ronald R de Krijger,
Winand N M Dinjens
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ABSTRACT: Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or platelet-derived growth factor receptor-α. However, a small subset of GISTs lacks such mutations and is termed 'wild-type GISTs'. Germline mutation in any of the subunits of succinate dehydrogenase (SDH) predisposes individuals to hereditary paragangliomas and pheochromocytomas. However, germline mutations of the genes encoding SDH subunits A, B, C or D (SDHA, SDHB, SDHC or SDHD; collectively SDHx) are also identified in GISTs. SDHA and SDHB immunohistochemistry are reliable techniques to identify pheochromocytomas and paragangliomas with mutations in SDHA, SDHB, SDHC and SDHD. In this study, we investigated if SDHA immunohistochemistry could also identify SDHA-mutated GISTs. Twenty-four adult wild-type GISTs and nine pediatric/adolescent wild-type GISTs were analyzed with SDHB, and where this was negative, then with SDHA immunohistochemistry. If SDHA immunohistochemistry was negative, sequencing analysis of the entire SDHA coding sequence was performed. All nine pediatric/adolescent GISTs and seven adult wild-type GISTs were negative for SDHB immunohistochemistry. One pediatric GIST and three SDHB-immunonegative adult wild-type GISTs were negative for SDHA immunohistochemistry. In all four SDHA-negative GISTs, a germline SDHA c.91C>T transition was found leading to a nonsense p.Arg31X mutation. Our results demonstrate that SDHA immunohistochemistry on GISTs can identify the presence of an SDHA germline mutation. Identifying GISTs with deficient SDH activity warrants additional genetic testing, evaluation and follow-up for inherited disorders and paragangliomas.Modern Pathology advance online publication, 23 November 2012; doi:10.1038/modpathol.2012.186.
Modern Pathology 11/2012; · 4.79 Impact Factor
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Histopathology 06/2012; 61(2):324-6. · 3.08 Impact Factor
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ABSTRACT: To report a large series of solitary and multiple myofibromas with systematic clinicopathological correlations.
We report on 114 patients with myofibromas, 97 of which were solitary and 17 multifocal. The age at presentation ranged from newborn to 70 years. All multifocal myofibromas and 91% of solitary myofibromas occurred in children. The head and neck region was the most common site (n = 43), followed by the trunk (n = 24), lower limbs (n = 14), upper limbs (n = 11), and viscera (n = 4). Solitary and multifocal myofibromas stained positively for smooth muscle actin (SMA) in 95% and 92% of cases, muscle-specific actin (MSA) in 75% and 50% of cases, and desmin in 10% and 14% of cases, respectively. Regressive features were seen in 34 solitary myofibromas and in nine multifocal myofibromas. Most patients were treated with complete excision (n = 79) or partial excision (n = 12). There were no recurrences after treatment.
Solitary and multiple myofibromas are benign tumours that predominantly occur in infancy and childhood. Myofibromas occur especially in the head and neck region, and are characterized by SMA and, to a lesser extent, MSA expression. The clinical course is self-limiting, and local excision appears to be sufficient.
Histopathology 04/2012; 60(6B):E1-11. · 3.08 Impact Factor
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ABSTRACT: This study investigated the optimal alveolar oxygen concentration and inflation pressure during ischemia that reduces lung ischemia-reperfusion injury (LIRI).
Male Sprague-Dawley rats (n = 66) underwent 150 minutes of left lung ischemia by hilar clamping at an airway inflation pressure (P) of 5 or 30 cm H(2)O and an oxygen (O) concentration of 0%, 30%, or 100% (P(5)O(0), P(5)O(30), P(5)O(100), P(30)O(0), P(30)O(30) and P(30)O(100) groups). Lungs preserved with 0% oxygen were inflated with 100% nitrogen. Measurements of arterial blood gas values, pulmonary compliance, histology, flow cytometry of bronchoalveolar lavage fluid were performed on day 2 postoperatively.
Inflation with 30 cm H(2)O resulted in increased partial pressure of arterial oxygen (Pao(2)) and lung compliance, decreased diffuse alveolar damage, and less infiltration of CD4(+) and CD8(+) lymphocytes and major histocompatibility complex class II-positive (MHCII(+)) antigen-presenting cells (APCs) in the left lung on day 2 compared with clamping at an airway inflation pressure of 5 cm H(2)O. The 100% oxygen groups demonstrated a lower Pao(2) and a decreased pulmonary compliance than 30% oxygen groups. More CD8(+) lymphocytes and MHCII(+) APCs were found in the P(5)O(100) group than in the P(5)O(0) and P(5)O(30) groups.
Alveolar inflation with a pressure of 30 cm H(2)O and an oxygen concentration of 30% decreases the severity of LIRI. The protective effect is mainly due to hyperinflation and, to a lesser extent, through oxygen concentration.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2012; 31(5):531-7. · 3.54 Impact Factor
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ABSTRACT: BACKGROUND.: Squamous carcinoma of the thyroid is a rare aggressive disease, resulting in poor prognosis. METHODS AND RESULTS.: We combined cisplatin with paclitaxel on a weekly basis as induction therapy, achieving a high cumulative dose, in a patient with squamous cell tumor of the thyroid with arterial encasement. After surgery, pathologic examination confirmed a complete resection of the primary tumor with clear margins, revealing a successful induction treatment with chemotherapy. CONCLUSIONS.: Our patient now has a recurrence-free survival of >20 months, longer than the mean survival described in the literature.
Head & Neck 01/2012; 34(1):131-4. · 2.40 Impact Factor
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ABSTRACT: Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS.
We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors.
The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%.
We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.
Journal of Clinical Oncology 09/2011; 29(30):4036-44. · 18.37 Impact Factor
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ABSTRACT: Testis-sparing surgery might benefit quality of life, but can only be applied with histological examination for the presence of invasive germ cell tumour components, and the precursor carcinoma in situ (CIS). Currently, diagnosis is based on paraffin-embedded tissue, therefore a delay in further surgery is mainly unavoidable. The aim was to develop an intraoperative assessment technique using alkaline phosphatase as a marker.
A total of 4093 snap-frozen samples and matched paraffin-embedded tissue of 1500 patients were included. Besides standard haematoxylin and eosin (H&E) staining, the direct enzymatic alkaline phosphatase reactivity (dAP) test (duration 15 min) was applied on frozen sections, while H&E and immunohistochemistry for detection of OCT3/4, α-fetoprotein, human chorionic gonadotrophin (hCG) and cytokeratin was performed on the paraffin-embedded slides. Endothelial cells served as control for the dAP test. Positive staining was found in all CIS (n=965), seminoma (n=1035) and embryonal carcinoma (n=584), either intratubular, microinvasive or invasive. Differentiated non-seminomas (n=1238) showed variable staining. No staining was identified in spermatocytic seminomas (n=5), testicular lymphomas (n=42), testicular rhabdomyosarcomas (n=7), Leydig cell tumours (n=31), Sertoli-cell-only nodules (n=4), (epi) dermoid cyst (n=16), normal testicular parenchyma (n=116), testicular torsion (n=32) and inflammation of the epididymis (n=19). The dAP test results matched H&E-stained parallel sections, as well paraffin-embedded tissue analysis, including immunohistochemistry.
The dAP test is an informative, reproducible and easy tool to diagnose CIS, (intratubular and microinvasive) seminoma and embryonal carcinoma on frozen tissue sections, being of great value in the context of sparing surgery.
Histopathology 02/2011; 58(3):440-6. · 3.08 Impact Factor
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ABSTRACT: Our aim was to evaluate the diagnostic accuracy of fine-needle aspiration cytology (FNAC) for Warthin tumors of the parotid gland.
All cytologic diagnoses of Warthin tumor between 1990 and 2007 were correlated with available histology. In addition, our results were compared to current literature.
In 310 cases, Warthin tumor was diagnosed by FNAC. In 133 cases, (43%) both cytology and histology were available. In 127 of these 133 cases (95.5%), the diagnosis Warthin tumor was confirmed by histology. In 4 cases (3%), a benign lesion was diagnosed and 2 (1.5%) revealed a malignant lesion. On review, those cytologic diagnoses were not certain. In the literature, 11 missed malignancies (5.4%) in 202 cases were reported.
The diagnostic accuracy of FNAC for the diagnosis of Warthin tumor is high and the percentage of missed malignant tumors is very low. Our results imply that a cytologic diagnosis of Warthin tumor may justify conservative treatment.
Head & Neck 12/2010; 32(12):1635-40. · 2.40 Impact Factor
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ABSTRACT: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity.
In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation.
Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up.
In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit.
Annals of Surgical Oncology 11/2010; 18(2):321-7. · 4.17 Impact Factor
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José Gaal,
Constantine A Stratakis,
J Aidan Carney,
Evan R Ball,
Esther Korpershoek,
Maya B Lodish,
Isaac Levy,
Paraskevi Xekouki,
Francien H van Nederveen, Michael A den Bakker,
Maureen O'Sullivan,
Winand N M Dinjens,
Ronald R de Krijger
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ABSTRACT: Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors (GISTs) specifically in the context of Carney-Stratakis syndrome. Previously, we have shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. We hypothesized that GISTs in patients with SDHx mutations would be negative immunohistochemically for SDHB as well. Four GISTs from patients with Carney-Stratakis syndrome and six from patients with Carney triad were investigated by SDHB immunohistochemistry. Five GISTs with KIT or PDGFRA gene mutations were used as controls. In addition, SDHB immunohistochemistry was performed on 42 apparently sporadic GISTs. In cases in which the SDHB immunohistochemistry was negative, mutational analysis of SDHB, SDHC, and SDHD was performed. All GISTs from patients with Carney-Stratakis syndrome and Carney triad were negative for SDHB immunohistochemically. In one patient with Carney-Stratakis syndrome, a germline SDHB mutation was found (p.Ser92Thr). The five GISTs with a KIT or PDGFRA gene mutation were all immunohistochemically positive for SDHB. Of the 42 sporadic tumors, one GIST was SDHB-negative. Mutational analysis of this tumor did not reveal an SDHx mutation. All SDHB-negative GISTs were located in the stomach, had an epithelioid morphology, and had no KIT or PDGFRA mutations. We show that Carney-Stratakis syndrome- and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT- or PDGFRA-mutated GISTs and a majority of sporadic GISTs. We suggest that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically. In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted.
Modern Pathology 10/2010; 24(1):147-51. · 4.79 Impact Factor
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Jos|[eacute]| Gaal,
Constantine A Stratakis,
J Aidan Carney,
Evan R Ball,
Esther Korpershoek,
Maya B Lodish,
Isaac Levy,
Paraskevi Xekouki,
Francien H van Nederveen, Michael A den Bakker,
Maureen O'Sullivan,
Winand NM Dinjens,
Ronald R de Krijger
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ABSTRACT: Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors (GISTs) specifically in the context of Carney–Stratakis syndrome. Previously, we have shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. We hypothesized that GISTs in patients with SDHx mutations would be negative immunohistochemically for SDHB as well. Four GISTs from patients with Carney–Stratakis syndrome and six from patients with Carney triad were investigated by SDHB immunohistochemistry. Five GISTs with KIT or PDGFRA gene mutations were used as controls. In addition, SDHB immunohistochemistry was performed on 42 apparently sporadic GISTs. In cases in which the SDHB immunohistochemistry was negative, mutational analysis of SDHB, SDHC, and SDHD was performed. All GISTs from patients with Carney–Stratakis syndrome and Carney triad were negative for SDHB immunohistochemically. In one patient with Carney–Stratakis syndrome, a germline SDHB mutation was found (p.Ser92Thr). The five GISTs with a KIT or PDGFRA gene mutation were all immunohistochemically positive for SDHB. Of the 42 sporadic tumors, one GIST was SDHB-negative. Mutational analysis of this tumor did not reveal an SDHx mutation. All SDHB-negative GISTs were located in the stomach, had an epithelioid morphology, and had no KIT or PDGFRA mutations. We show that Carney–Stratakis syndrome- and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT- or PDGFRA-mutated GISTs and a majority of sporadic GISTs. We suggest that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically. In case of negative SDHB staining in GISTs, Carney–Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted.Keywords: Carney–Stratakis syndrome; Carney triad; gastrointestinal stromal tumor; immunohistochemistry; SDHB
Modern Pathology 09/2010; 24(1):147-151. · 4.79 Impact Factor
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ABSTRACT: Gene-engineered T cell therapy represents a promising strategy to treat cancers. To enable pre-selection of patients sensitive to this type of treatment we have setup and validated a T cell activation assay to test antigen expression on patient-derived tumor tissues. Chimeric antibody-based receptor (CAR) directed against CAIX, currently used in a clinical trial to treat RCC patients, was used as a model receptor. Primary human T cells expressing CAIX CAR were able to respond to CAIX-positive but not CAIX-negative tumor tissue and showed an increased production of IFNgamma, TNFalpha, IL-10 and IL-4, but not IL-2 or IL-5. Tumor tissue driven responses of primary T cells were paralleled by NFAT activation measured in CAR-transduced Jurkat T cells, which was shown to be triggered in a CAR and antigen-specific manner. Next, the reporter gene assay was applied to two independent PSMA CARs, which both mediated NFAT activation in response to tumor tissue. Taken together, a sensitive and donor-independent assay was established to measure T cell activation upon exposure to patient-derived tumor tissue, which may facilitate pre-selection of patients for clinical adoptive T cell therapy.
Journal of immunological methods 05/2010; 359(1-2):11-20. · 2.35 Impact Factor
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ABSTRACT: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation.
One hundred and seventy cases of SCLC, LCNEC and cases diagnosed as neuroendocrine lung carcinoma before LCNEC had been established as a diagnostic category were retrieved from the archives of the assessor's institutes. A representative haematoxylin and eosin section from each case was selected for review. Batches of cases were circulated among nine pathologists with a special interest in pulmonary pathology. Participants were asked to classify the cases histologically according to the 2004 World Health Organization (WHO) criteria. The diagnoses were collected and kappa values calculated. Unanimity of diagnosis was achieved for only 20 cases; a majority diagnosis was reached for 115 cases. In 35 cases no consensus diagnosis could be reached. There was striking variability amongst assessors in diagnosing SCLC and LCNEC. The overall level of agreement for all cases included in this study was fair (kappa=0.40).
Using non-preselected cases, the morphological WHO criteria for diagnosing SCLC and LCNEC leave room for subjective pathological interpretation, which results in imprecise categorization of SCLC and LCNEC cases.
Histopathology 02/2010; 56(3):356-63. · 3.08 Impact Factor
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ABSTRACT: Mutations in TP53 underlie the development of malignant peripheral nerve sheath tumors (MPNSTs) in animal models, but there is controversy regarding the extent of TP53 mutations in human MPNSTs. We assessed the TP53 mutation frequency in 145 consecutive cases from our department over 36 years; 88 cases were histologically confirmed as MPNSTs, and corresponding clinical data were reviewed. Mutation analysis of TP53 Exons 4 to 9 on DNA from formalin-fixed, paraffin-embedded specimens was performed by bidirectional DNA sequencing. Tumors were localized in the extremities (n = 34), trunk (n = 34), or head and neck (n = 20). A minority of patients (n = 26, 30%) had neurofibromatosis type 1 (NF1); in these patients, the diagnosis of MPNST was made at younger ages (33 [SD, 3.6] years vs 49 [SD, 2.9] years in NF1 vs non-NF1; p = 0.003). High p53 protein expression was detected in 18 (21%) of 86 cases by immunohistochemistry. TP53 mutations were detected in 17 (24%) of 72 evaluable tumors, of which 36% were from NF1 patients. TP53 mutation and strong p53 immunostaining were positively correlated (p = 0.002); high proliferation indices correlated with cellular epithelioid and storiform growth patterns. These results indicate that TP53 mutations are relatively rare in human MPNST and that they are not positively correlated with the presence of NF1.
Journal of Neuropathology and Experimental Neurology 12/2009; 69(1):16-26. · 4.26 Impact Factor
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ABSTRACT: Malignant vascular tumors are rare and angiosarcomas of the breast in patients under 21 years of age are exceedingly uncommon. In this report an angiosarcoma in the breast of a 14-year-old girl is described. She died nine months after mastectomy with recurrent disease in the bones and the contralateral breast. The etiology of most primary angiosarcomas is unknown. Secondary angiosarcomas can develop after radiotherapy and chronic lymphedema. The histology of this angiosarcoma is illustrated.
Rare tumors 01/2009; 1(2):e38.
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ABSTRACT: Lung ischemia-reperfusion injury (LIRI) is a risk factor for primary acute graft failure following lung transplantation. LIRI hereby contributes to morbidity and mortality after lung transplantation. We have previously shown that surfactant pretreatment ameliorates LIRI up to 1 week after reperfusion. However, the impact of surfactant pretreatment on long-term outcome following LIRI is unknown. Therefore, the objective of this study was to investigate the effect of surfactant pretreatment on long-term outcome following LIRI.
Male Sprague-Dawley rats (n=63) were randomized to receive intratracheally administered porcine surfactant (400mg/kg) or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia by clamping the bronchus, pulmonary artery and vein of the left lung. A third group was sham-operated; a fourth group served as unoperated controls. Animals were killed on day 30 or 90 after surgery. Arterial oxygenation and lung compliance were determined. Broncho-alveolar lavage fluid (BALf) was collected to assess surfactant function and alveolar protein. Leukocyte infiltration was determined by flowcytometry in BALf, lung tissue and thoracic lymph nodes. Lungs of three animals per group were used for histological assessment.
Lung compliance was lower on day 30 and day 90 after LIRI than in sham-operated controls (day 30 V(max) 6.1+/-2.1 vs 12.6+/-1.3, day 90 6.9+/-3.0 vs 12.1+/-1.6; C(max) day 30 0.49+/-0.17 vs 1.08+/-0.21, day 90 0.67+/-0.31 vs 1.11+/-0.17). Furthermore, the number of CD45RA(+)-lymphocytes in left lung tissue was decreased on day 90 compared to unoperated animals (230.633+/-96.770 vs 696.347+/-202.909) and the number of macrophages elevated in left BALf on day 90. HE slides of LIRI animals were scored as fibroproliferative with moderate atelectasis. Surfactant pretreatment improved lung compliance (V(max) day 30 11.7+/-1.8, day 90 11.1+/-1.2; C(max) day 30 1.04+/-0.23, day 90 1.16+/-0.21) and normalized the number of CD45RA(+)-lymphocytes (769.555+/-421.016) in left lung tissue. Furthermore lung architecture on HE slides was on return to normal. However, more CD5(+)CD4(+)-lymphocytes on day 30 (754.788+/-97.269 vs 430.409+/-109.909) and more macrophages on day 90 (2.144.000+/-630.633 vs 867.454+/-383.220) were measured in pretreated lung tissue compared to LIRI animals.
Severe LIRI caused extensive pulmonary injury up to 90 days postoperatively. Surfactant pretreatment normalized pulmonary function, but resulted in an increased number of CD5(+)CD4(+)-cells and macrophages in lung tissue.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 01/2009; 35(2):304-12; discussion 312. · 2.40 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. Fifteen patients with locally advanced (n=9) and/or metastatic GIST (n=6) were treated with imatinib followed by resection. Detailed histopathological examination was performed before and after treatment with imatinib, which was given for a median of 11 months before surgery. Ten patients showed a radiographic partial response, four patients had stable disease, and one patient progressed. At the time of surgery, the median tumor diameter was 6.5 cm. In all the nine patients with locally advanced GIST, a R0 resection could be performed. Histopathological examination showed imatinib effects in all tumors, including the case with progressive disease. All patients with locally advanced disease (n=9) were alive after a median follow-up of 40 months (range: 18-59), of which seven patients were free of disease. Four of the six patients treated for metastatic GIST died of disease after 30, 45, 50, and 74 months of follow-up. Remarkably, in five of six patients in whom CD117 expression was diminished or lost in the resection specimen, disease recurrence was observed. In patients with retained CD117 expression, one of the nine patients had recurrent disease. In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.
Anti-Cancer Drugs 07/2008; 19(6):607-12. · 2.41 Impact Factor
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ABSTRACT: Glomus tumors usually occur in the acral soft tissue and rarely in visceral locations, such as the stomach, intestines, mediastinum, lung, pancreas, bladder, and vagina. The authors present a 74-year-old woman with an exceptionally large glomus tumor of the mesentrium with malignant features. Previously reported cases of intraabdominal glomus tumor in the abdominal cavity exhibited benign behavior and few cases with metastatic disease. Criteria for malignancy in acral glomus tumors, such as unusually large size, infiltrative growth, necrosis, nuclear atypia, and mitotic activity, seem not to translate to abdominal glomus tumors. As very few intraabdominal glomus are described, the malignant potential of these tumors stays uncertain for longer period.
International Journal of Surgical Pathology 06/2008; 16(4):440-2. · 1.00 Impact Factor
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ABSTRACT: In this report, we describe a case of domestically acquired particulate lung disease (DAPLD) or "hut lung" in a 59-year-old woman of Moroccan descent who emigrated to the Netherlands, having lived in an rural area for most her life. She presented with obstructive lung disease and with signs of mediastinal fibrosis which were shown to be caused by massive enlargement of mediastinal lymph nodes. To the best of our knowledge, this is the first case of DAPLD from Morocco and the first report of a case of DAPLD mimicking mediastinal fibrosis.
Annals of Diagnostic Pathology 05/2008; 12(2):118-21. · 0.88 Impact Factor
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ABSTRACT: Nitrofurantoin is a commonly used drug in the treatment and prevention of urinary tract infections. Many adverse effects of nitrofurantoin have been documented, including aplastic anemia, polyneuritis, and liver and pulmonary toxicity.
We describe the clinical history and the autopsy findings in a 51-year-old woman with lung fibrosis of unknown etiology. She had a history of recurrent urinary tract infections, treated with nitrofurantoin for many years. She was referred to our hospital for screening for lung transplantation because of severe pulmonary restriction and dyspnea. Unfortunately, she died as a result of progressive respiratory insufficiency. At autopsy bilateral patchy, sharply circumscribed fibrotic areas in the upper and lower lobes of the lungs were seen with honeycombing. Microscopically, end-stage interstitial fibrosis with diffuse alveolar damage was observed. Due to the atypical distribution of the fibrosis involving both the lower and upper lobes of the lung, the microscopic pattern of the fibrosis and the history of long-term nitrofurantoin use, we concluded that this drug induced the lung fibrosis. The recurrent urinary tract infections were probably caused by a diverticulum of the urinary bladder, which was discovered at autopsy.
This case shows that the use of nitrofurantoin may cause severe pulmonary disease. Patients with long-term use of nitrofurantoin should be monitored regularly for adverse pulmonary effects.
Journal of Medical Case Reports 02/2008; 2:169.
