Document YroLgdeN5veNXOX2qXn4pGL8n

Patel et al attributed to multiple previous transfusions (Fig 1C, white arrow). Immunohistochemically, the malignant lymphoid cells were positive for B-cell marker CD20, with 90% ofthem expressing the proliferative marker MIB-1 (Ki-67). They were negative for bcl-2. In situ hybrid ization for Epstein-Barr virus (EBV)-encoded small RNA was nega tive. The overall features were consistent with diffuse large B-cell lymphoma involving primarily the liver. The patient then underwent three courses of chemotherapy of rituximab, prednisolone, epirubicin, cyclophosphamide and vincristine sulfate. PET/CT was repeated for reassessment. The previously noted numerous hypermetabolic lesions throughout both lobes have almost completely resolved, leaving behind only a few scattered tiny hypodensities in both lobes which do not demonstrate discernable FDG uptake (Fig 1D, arrows), in keeping with complete metabolic response to treatment. Primary hepatic lymphoma (PHL) is extremely rare and only accounts for 0.016% of all non-Hodgkin's lymphoma.1 PHL has been reported to occur more frequently in the context of chronic hepatitis C virus infection and immunosuppression, including infec tion with HIV.2,3 Clinical features include abdominal pain, constitu tional symptoms, and hepatomegaly. The predominant histological type is diffuse large B-cell lymphoma.2 Three patterns of hepatic in volvement have been described, including a solitary mass, multiple liver masses, and diffuse infiltration.3,4 There is a scarcity of data on imaging studies in PHL. On ultrasonography, hepatic lymphomas usually present as hypoechoic and homogenous lesions. Occasionally, anechoic lesions maybe found with posterior enhancement.5 On CT, hepatic lymphomas are usually hypodense, and rim enhancement may be present in the portal venous phase.3 Magnetic resonance imaging show PHL as hypointense lesions in Tl-weighted images and hyperintense in T2-weighted scans.3,6 However, similar imaging fea tures may be observed in liver abscess or metastases.6,7 PET/CT was valuable in our case, as being a whole-body functional scan, other sites of involvement were excluded, thereby demonstrating the primary hepatic origin of the lymphoma. In agreement of the study of De Renzo et al,8 PET/CT was a useful tool for response assessment. Our case arose in the setting ofchronic hepatitis B virus infection and heavy previous immunosuppression for the autoimmune hemolytic ane mia. Since EBV was absent, the case was different from EBV-related lymphomas arising in immunocompromised or organ-allograft pa tients. However, our case confirmed the previously observed associa tion between an immunocompromised state, chronic infection with a hepatotrophic virus, and PHL.1,3 Winnie K.S. Chan Department of Diagnostic Radiology, University of Hong Kong, Hong Kong Eric W.C. Tse Department of Medicine, University of Hong Kong, Hong Kong Yuen-Shan Fan Department of Pathology, Queen Mary Hospital, Hong Kong Jingbo Zhang Department of Diagnostic Radiology, University of Hong Kong, Hong Kong Yok-Lam Kwong Department of Medicine, University of Hong Kong, Hong Kong Pek-Lan Khong Department of Diagnostic Radiology, Queen Mary Hospital, University of Hong Kong, Hong Kong AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Noronha V, Shafi NQ, Obando JA, et al: Primary non-Hodgkin's lymphoma of the liver. Crit Rev Oncol Hematol 53:199-207, 2005 2. De Renzo A, Perna F, Persico M, et al: Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma. Eur J Haematol 81:51-57, 2008 3. Rizzi EB, Schinina V, Cristofaro M, et al: Non-hodgkin's lymphoma of the liver in patients with AIDS: Sonographic, CT, and MRI findings. J Clin Ultrasound 29:125-129, 2001 4. Coenegrachts K, Vanbeckevoort D, Deraedt K, et al: MRI findings in primary non-Hodgkin's lymphoma of the liver. JBR-BTR 88:17-19, 2005 5. Appelbaum L, Lederman R, Agid R, et al: Hepatic lymphoma: An imaging approach with emphasis on image-guided needle biopsy. Isr Med Assoc J 7:19-22, 2005 6. Maher MM, McDermott SR, Fenlon HM, et al: Imaging of primary nonHodgkin's lymphoma of the liver. Clin Radiol 56:295-301, 2001 7. Doyle DJ, Hanbidge AE, O'Malley ME: Imaging of hepatic infections. Clin Radiol 61:737-748, 2006 8. De Renzo A, Perna F, Persico M, et al: 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the evaluation of early response in a primary hepatic lymphoma. Br J Haematol 133:580, 2006 DOI: 10.1200/JCO.2008.18.5413; published online ahead of print at www.jco.org on October 27, 2008 Malignant Pleural Mesothelioma After Household Exposure to Asbestos total atelectasis of the right lung, and mild pleural thickening with multiple nodular pleural masses (Fig 1, arrows). Pleural biopsy revealed a sarcomatoid mesothelioma. The cells exhibited mild to A 70-year-old female with diabetes, hypertension, and a 20 pack-year smoking history presented with new onset cough. She had pleuritic chest pain with dyspnea on exertion, without any fever or hemoptysis. She reported a 10-pound weight loss over 2 months with occasional night sweats. She quit smoking 25 years before diagnosis and denied any occupational exposure. Patient's husband of 35 years had died of mesothelioma 12 years earlier. Her second-hand exposure was related to shaking out and washing her husband's clothes. Her husband worked in a construction business spraying asbestos (crocidolite) as a fire repellant. Computed to mography (CT) scan revealed a large right pleural effusion, near Fig 1. 5480 2008 by American Society of Clinical Oncology Journal of Clinical Oncology Information downloaded from jco.ascopubs.org and provided by HAM-TMC LIBRARY on June 19, 2009 from 192.68.30.2. Copyright 2008 by the American Society of Clinical Oncology. All rights reserved. Diagnosis in Oncology moderate nuclear atypia and frequent mitoses. The cells appeared spindled and were growing in a storiform pattern with short fasci cles. Immunohistochemistry was positive for CK 5/6 and focally for calretinin. WT-1, TTF-1, carcinoembryonic antigen, Ber-EP4, CD34 and Bcl-2 were negative, consistent with a sarcomatoid mesothelioma. Additional pleural biopsies done revealed sarcoma toid mesothelioma. She received five cycles of cisplatin (75 mg/m2) and pemetrexed (500 mg/m2), but progressed on follow-up CT scans. She progressed on gemcitabine (1,000 mg/m2). Over the ensuing months, she developed multiple subcutaneous nodules (Fig 2). She was begun on vinorelbine (25 mg/m2) and cisplatin (75 mg/m2), but developed grade 4 neutropenia with one cycle. Pres ently she is on single-agent vinorelbine. A 77-year-old female with a history of angina, hypertension, congestive heart failure, and ductal carcinoma in situ on tamoxifen was found to have a right upper lobe mass on surveillance x-rays over 6 years. She worked as a grocery store clerk. She had a 70 pack-year history, but quit 10 years prior. She did not give a history of direct exposure to asbestos; however, she shook out and washed her husband's clothes daily. Her husband of 53 years was a pipe fitter and had died of mesothelioma. An increase in size of the mass prompted CT and positron emission tomography scans. She under went a right upper lobectomy for stage IA adenocarcinoma. At the time she had a pleural-based opacity on the opposite lung. Surveil lance CT scans following the lobectomy revealed that the left pleural-based 1.5-cm X 1-cm nodule which had been present at the time of right upper lobectomy, increased to 2.7 cm X 2.3 cm over 4 years (Fig 3, arrows). An ultrasound-guided needle biopsy of the pleural mass revealed bland, epithelioid cells growing in both papillary and solid configurations. Hematoxylin and eosin stain of pleural biopsy showed mildly atypical, monomorphic cells with moderate amounts of eosinophilic cytoplasm with scarce mitotic activity (Fig 4A). Hematoxylin and eosin and Papanicolaou stain of pleural mass shows focal areas of tubular and papillary growth (Fig 4B). By immunohistochemistry, the cells were cytokeratin (CK) AE1/3, CK5/6, CK7, calretinin (Fig 4C), and WT-1 positive. In the setting of an appropriate panel ofantibodies, calretinin stain identifies Fig 2. Fig 3. the cells as mesothelial and helps exclude carcinoma. They were neg ative for Ber-EP4, TTF-1, mucin and carcinoembryonic antigen (not shown). The morphology, immunophenotype, and clinical picture were thus consistent with malignant epitheloid-type mesothelioma. Here we describe two female patients who never had direct asbestos exposure, but developed mesothelioma from second hand asbestos exposure, perhaps by washing their husbands' clothes. Asbestos, a naturally occurring fiber, is widely used in many industries. Inhalation of asbestos fibers can result in a distinct patho logic process, ranging from benign plaques to malignant mesotheli oma. Malignant pleural mesothelioma (MPM) is an uncommon, fatal neoplasm arising from mesothelial cells lining the pleura. In the United States, MPM occurs in approximately 2,500 persons per year, with 20% being women.1 The peak global incidence of asbestosrelated disease is expected to occur 30 to 40 years after the period of peak usage. The disease is expected to increase in incidence globally until 2020.2 There is a clear link between exposure to asbestos and MPM. An inverse relationship exists between intensity of asbestos exposure and length of the latency period. The construction industry accounted for nearly 15% of decedents with MPM, followed by ship and boat building and repairing, industrial and miscellaneous chem icals, petroleum refining, and electric light and power. Interestingly, housewives had the second highest mortality rate (6.8%) after manag ers and administrators (7.6%) in 1999.1 Bystander risks related to asbestos exposure have been described previously.3 The high me sothelioma risk was predominantly influenced by exposure to amphibole asbestos (crocidolite and amosite), which reached its peak usage in the 1960s and thereafter declined. Rates ofmesothelioma peaked for males in early 1990s and have since declined, but remained steady for females throughout.4 Some countries and cultures exposed to asbestos through common household tasks like whitewashing the home have higher rates of mesothelioma in females.5,6 A report from Germany reported five cases of MPM in housewives, which were attributed to inhalative household contact with asbestos. An occupational history of asbestos exposure could not be revealed. A causal relationship between the fatal disease and the inhalative household contact with asbestos was established based on the cleaning of asbestos contami nated workclothes ofthe husbands.7 An Italian study noted that family members of asbestos workers were at higher risk of developing malig nant mesothelioma with increased standardized mortality ratio for pleural cancer 21 observed v 1.2 expected; standardized mortality ratio = 18.00; 95% CI, 11.14 to 27.52).8 An Australian study reported higher MPM rates in male subjects and those with more than 15 years since first exposure, but women had a steeper doseresponse curve.9 The steeper dose-response slope for women was www.jco.org 2008 by American Society of Clinical Oncology Information downloaded from jco.ascopubs.org and provided by HAM-TMC LIBRARY on June 19, 2009 from 192.68.30.2. Copyright 2008 by the American Society of Clinical Oncology. All rights reserved. 5481 Patel et al Fig 4. thought to be due to smaller lung volume with higher forced expiratory flow rate and a higher forced expiratory volume in 1 second/forced vital capacity ratio. This may lead to greater alveolar fiber deposition and greater fiber retention than in men with larger lungs. In a multicenter report, moderate or high probability of domestic exposure was associated with an increased risk of devel oping MPM in cases without evidence of occupational exposure to asbestos.10 This corresponded to three situations: cleaning asbestos-contaminated clothes, handling asbestos material, and being in the presence of asbestos material susceptible to damage. The largest case series of second-hand exposure consists of 32 patients over 15 years.11 Relationships were wife,15 daughter,11 son3 and others.3 Occupations of the workers included shipyard,13 insulator,7 and others.12 Of the 27 pleural cases, 13 were epithelial, five were fibrous, three were biphasic, and six were not specified; of the five peritoneal cases, four were epithelial and one was fibrous. Latency was greater than 40 years in 27 cases; six cases were age 40 to 49 years and 17 were 60 years or older.11 In contrast to the long latency period reported in above study, an aggressive course with a short latency period in three bystander cases has been reported.12 Exposure to the crocidolite form of asbestos was most often asso ciated with the development ofMPM.12,13 A study to determine the lung tissue concentration of asbestos in persons with MPM exam ined 73 cases and estimated highest increase in relative risk for crocidolite.13 Crocidolite asbestos, also known as blue asbestos, accounted only for approximately 4% of the total asbestos used in the United States. These straight, needle-like fibers are easy to inhale and remain in the lungs indefinitely. Incidence of MPM is approximately 18% to 24% in those who have mined this form of asbestos.14-16 Epithelial mesothelioma (50% to 75%) is the most common histologic subtype, with a better prognosis then sarcoma toid (15% to 20%) or mixed-type (20% to 30%) mesotheliomas.17-19 The differential diagnosis on biopsy varies according to the histo logic type. Epithelioid-type mesothelioma must be distinguished from primary or metastatic carcinoma, while sarcomatoid me sothelioma can mimic organizing effusion, sarcoma, or other spin dled tumors of the pleura such as solitary fibrous tumor. MPM remains an aggressive tumor, usually associated with a poor prog nosis. Male sex, older age, weight loss, chest pain, poor perfor mance status, low hemoglobin, leukocytosis, thrombocytosis, and nonepithelial cell type (P < .05) are poor prognostic factors. Most patients have stage III (48%) or IV (40%) disease at the time of presentation,andremainunresectable.20Responserateswithchemotherapy remain low, though combination regimens have better response rates compared to single agent chemotherapy. Novel chemotherapy regimens with definite activity such as antifolate (pemetrexed or raltitrexed) -platinum combinations, and new ra diotherapy techniques such as intensity-modulated radiation ther apy have shown promising results. Currently agents targeting epidermal growth factor receptor, vascular endothelial growth fac tor, and platelet-derived growth factor are under evaluation in MPM. MPM remains an aggressive malignancy despite treatment, with a median survival of 6-11 months and 1-year survival ranging between 18.4% and 57.6%. Early diagnosis is thus a key element in successful treatment, and awareness ofthis entity should be height ened. In the differential diagnosis of a mass involving pleura and lung, physicians should consider the possibility of mesothelioma both with a history of direct asbestos exposure, but also in the setting of secondary asbestos exposure. Anush V. Patel Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY Paul N. Bogner Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY Donald Klippenstein Department of Radiology, Roswell Park Cancer Institute, Buffalo, NY Nithya Ramnath University of Michigan Comprehensive Cancer Center, Ann Arbor, MI AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. National Institute of Occupational Safety and Health: Work-Related Lung Disease (WoRLD) Surveillance System: Malignant Mesothelioma, 2003. http:// www2.cdc.gov/drds/WorldReportData/ 2. Robinson BW, Lake RA: Advances in malignant mesothelioma. N Engl J Med 353:1591-1603, 2005 3. Antman KH: Current concepts: Malignant mesothelioma. N Engl J Med 303:200-202, 1980 4. National Cancer Institute: SEER Database: Invasive Mesothelioma, 2005. http://seer.cancer.gov/csr/1975_2005/results_merged/sect_17_mesothelioma.pdf 5. Metintas S, Metintas M, Oner U, et al: Malignant mesothelioma due to environmental exposure to asbestos: Follow-up of a Turkish cohort living in a rural area. Chest 122:2224-2229, 2002 6. Metintas M, Hillerdal G, Metintas S: Malignant mesothelioma due to environmental exposure to erionite: Follow-up of a Turkish emigrant cohort. Eur RespirJ 13:523-526, 1999 7. Schneider J, Woitowitz HJ: Asbestos-related mesotheliomas in house wives from indoor air pollution [in German]. Zentralbl Hyg Umweltmed 196:495 503, 1995 8. Ferrante D, Bertolotti M, Magnani C, et al: Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. Environ Health Perspect 115:1401-1405, 2007 5482 2008 by American Society of Clinical Oncology Journal of Clinical Oncology Information downloaded from jco.ascopubs.org and provided by HAM-TMC LIBRARY on June 19, 2009 from 192.68.30.2. Copyright 2008 by the American Society of Clinical Oncology. All rights reserved. Diagnosis in Oncology 9. Reid A, Berry G, de Klerk N, et al: Age and sex differences in malignant mesothelioma after residential exposure to blue asbestos (crocidolite). Chest 131:376-382, 2007 10. Magnani C, Agudo A, Gonzalez CA, et al: Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos. Br J Cancer 83:104-111, 2000 11. Miller A: Mesothelioma in household members of asbestos-exposed workers: 32 United States cases since 1990. Am J Ind Med 47:458-462, 2005 12. Ampleford EJ, OharJ: Mesothelioma: You do not have to work for it. Diagn Cytopathol 35:774-777, 2007 13. McDonald JC, Armstrong BG, Edwards CW, et al: Case-referent survey of young adults with mesothelioma: I. Lung fibre analyses. Ann Occup Hyg 45:513-518, 2001 14. Roggli VL, Pratt PC, Brody AR: Asbestos fiber type in malignant mesothe lioma: An analytical scanning electron microscopic study of 94 cases. Am J Ind Med 23:605-614, 1993 15. Langer AM, Nolan RP: Asbestos in the lungs of persons exposed in the USA. Monaldi Arch Chest Dis 53:168-180, 1998 16. Hansen J, de Klerk NH, Hobbs MS, et al: Environmental exposure to crocidolite and mesothelioma: Exposure-response relationships. Am J Respir Crit Care Med 157:69-75, 1998 17. Johansson L, Linden CJ: Aspects of histopathologic subtype as a prognos tic factor in 85 pleural mesotheliomas. Chest 109:109-114, 1996 18. Attanoos RL, Gibbs AR: Pathology of malignant mesothelioma. Histopathology 30:403-418, 1997 19. World Health Organisation: International Histological Classifications of Tumours.: Histological Typing of Lung Tumours, Vol. 1 (ed 3). Geneva, Switzer land, World Health Organisation, 1999, pp 128-135 20. Flores RM: The role of PET in the surgical management of malignant pleural mesothelioma. Lung Cancer 49:S27-S32, 2005 (suppl 1) DOI: 10.1200/JC0.2008.18.8268; published online ahead of print at www.jco.org on October 27, 2008 Spontaneous Pneumocephalus Associated With Recurrent Colorectal Carcinoma A 69-year-old male with carcinoma of the sigmoid colon metastatic to the liver underwent surgical resection of the primary tumor and subsequent chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab. The pa tient developed lower abdominal pain and weight loss 8 months after completion of therapy. A complete diagnostic work-up revealeda7.1- X 4-cm tumor recurrence at the surgical anastomosis. Systemic palliative therapy with infusional fluorouracil, leucovorin, and irinotecan plusbevacizumab was administered for 4 months until enlargement of a pelvic lesion. Subsequent systemic palliation was administered with a combination of FOLFOX plus cetuximab until further disease progression was once again docu mented. Four days after completion of this regimen, the patient developed tightness in the muscles ofthe thighs and uncontrollable pain in the perineal area prompting a hospital admission. Soon after, the patient became unresponsive, requiring airway protec tion and respiratory support. Physical examination was remark able for edema of the right proximal thigh and nuccal rigidity. Imaging studies of the brain, chest, abdomen, and pelvis demon strated an extensive air pattern in the soft tissues surrounding the rectal mass into pelvis tracking down to the thighs (Fig 1A, arrows), and extending along a right sacral nerve root (Fig 1B; T, large lobulating mass with air inside; bottom arrow indicates air in sacral space) into the spinal canal (Fig 1C, arrows). The air could be followed in the spinal canal all the way up to the brain (Fig 1D, arrows). The patient expired within few days of the complication. Spontaneous pneumocephalus is a common complication in neurosurgical patients and is usually associated with trauma, tumors, infection, or during intracranial surgery.1 However, its occur rence in patients with cancer has only been reported with tumors involving the brain parenchyma,2 otic nerve,3 nasopharynx,4,5 and spine.6 Other commonly described settings include ventricular peritoneal shunts,7,8 thoracotomy,9 temporal bone fractures,10 and displacement of ventriculo-peritoneal shunts into the sigmoid co lon.11 Pneumocephalus must be considered whenever the dura is dysrupted, especially if a CSF leak is present. Therapy depends on the degree oftension, symptomatology, and etiology. The develop ment of a spontaneous pneumocephalus in the patient presented herein most likely resulted from a fistulous tract developing between the tumor and a sacral nerve root (Fig 1B). To our knowledge, this is the first case describing a spontaneous gas communication between a malignancy of the gastrointestinal tract into the spinal canal and sec ondary meningitis. Angela Torres Department of Research, Oncology Consultants, Physicians Associates, Houston, TX Fig 1. www.jco.org 2008 by American Society of Clinical Oncology Information downloaded from jco.ascopubs.org and provided by HAM-TMC LIBRARY on June 19, 2009 from 192.68.30.2. Copyright 2008 by the American Society of Clinical Oncology. All rights reserved. 5483