Annab of Oncology 3: 321-323, 1992.
Letters to the editor Colorectal cancer presenting as isolated skull metastasis Bone metastases are very common in some neoplasms, but are clinically uncommon in colorectal cancer, although they have been reported in 20% of postmortems on patients treated for colorectal neoplasms [1|. We report a very unusual case of a patient suffering a VI cranial nerve palsy secondary to a sphenoidal bone deposit as initial manifestation of a colorectal rumour.
Case report
pain without rebound tenderness on palpation. A barium enema showed a perforated left colonic tumour, and exteriorization of the perforation and peritoneal lavage were performed. Adenocarcinoma was determined upon microscopical examination of the descending colon specimen (Fig. 2). Immunochemistry showed an intense and diffuse immunoreactivity when CEA was added. Lymph nodes were positive for malignant cells. Intraoperatory survey of the liver showed diffuse infiltration by metastases. The patient developed widespread pathological fractures and hypercalcemia. He suffered continuously from severe pain, followed by loss of appetite and lethargy, and died three months after presentation.
A 55-yr-old male was admitted to the hospital because of sudden development of diplopia. He had no evidence of weight loss, change in bowel habits, melena, or flank or abdominal pain. Physical examination showed a VI left cranial nerve palsy (paralysis of abduction and a convergent strabismus) but no other neurologic deficit. The remaining examinations furnished no additional information. A computed tomogram of the brain showed a lytic lesion on the body of the sphenoid bone (Fig. 1A) that was enhanced by intravenous contrast (Fig. IB). There were no brain lesions or ventricular enlargements.
Fig. 2. A malignant gland composed of columnar cells in a patient with colonic adenocarcinoma.
Discussion In a recent report on patients with colorectal carcinoma, bone metastases were diagnosed one to 100 months (median 21) after surgical treatment of the primary tumor. Most patients presented with bone pain. Lumbar spine was the most frequent site of metastases (62%), while skull lesions were Fig. I. (A) Non-enhanced CT scan. A lytic lesion (arrows) affecting found in 6% of the cases. Radiological findings were variable, the body of the sphenoid bone and clivus; (B) Contrast-enhanced with lytic lesions being the most common. Communication CT scan. The same lesion showing irregular enhancement. between the veins of the lower rectum, pelvis and vertebral system may account for the frequency of metastasis to the lumbar spine [1, 2]. The results of blood analyses of hemoglobin, serum calNeoplastic involvement of the skull is most frequently by cium, alkaline phosphatase, SGOT, SGPT, total bilirubin, metastasis or invasion from adjacent neoplasms, followed by albumin and total protein were within normal range. Serum myeloma and lymphoma, all of them with a radiological carcinoembryonic antigen (CEA) was 1870 U/L. The chest appearance of multiple lucent or lytic lesions. Infrequently, x-ray film revealed clear lung fields. No evidence of metas- metastases present as solitary lesions in skull base, and diftases was found on liver sonography. Results of conventional ferential diagnosis with plasmacytoma and chordoma must radiography of the axial skeleton were normal. A bone scan be considered in adult patients [3|. showed widespread metastases. Microscopical examination It should be noted that neurological symptoms in patients of bone marrow yielded negative results. The cerebrospinal with metastatic colorectal cancer are rare. Indeed, in the literature reviewed, only three patients treated for colorectal fluid examination failed to reveal malignant cells. During his hospital stay the patient presented abdominal cancer showed cranial nerve palsy, but in none were neuro-
322 logical symptoms evident as manifest features of the neoplasm [4].
my 11 and 13-year-old daughters who arrived at the right scores without even a pocket calculator!
J. L. Rodriguez-Garcia, J. Martinez-San-Millan, C. Cuesta, J. Perales, G. Fraile & M. Serrano From the Departments of Internal Medicine, Radiology and Pathology, Hospital Ramon y Cajal, Carretera de Colmenarkm. 9,100 28034 Madrid, Spain
R. C. F. Leonard Department of Clinical Oncology, Western General Hospital, Edinburgh, EH4 2XU, U.K.
References
The above letter was referred to the author, who responds as follows:
Dr. Leonard and his coworkers address several points in their letter, the first of which concerns the methods they used to describe and validate their prognostic index for low-grade lymphomas [1]. I agree that dividing their patients into two groups learning and test subgroups, permits a prospective validation of the results, which has rarely been done in early analyses of this type. The test group comprises all patients from one center that had been excluded from the first analysis. While this permits validation of results by an independent procedure, the best method for doing this would have been to randomly allocate patients to the learning or test subgroups or to test the described index on an independent set of data [2]. The main point of their letter concerns the variables to be Prognosis in low grade lymphoma included in such an analysis of prognostic factors in order to I would like to reply, on behalf of my co-authors, to Professor define a prognostic Index useful to others. The primary reaCoifEer's generally helpful leading article which accompanied son for doing such analyses is to propose a means for stratiour paper in volume 2 of Annals of Oncology, pp. 655-662. fying patients before treatment into subgroups of known He stresses the common features amongst the various grades prognosis and then to propose the best available treatment of follicular lymphomas in contrast to diffuse low grade lym- for each of these subgroups. Only explanatory variables studied at the time of patients phoma However he fails to mention the one feature which strikes the physician managing patients with various types of accrual should be included in such analyses, and if a variable low grade lymphoma, which is the long duration of the was not included in the study design it is too late to have it natural history, i.e. the clinical aggressiveness. Our analysis measured at the time of analysis. This selection and definiwhich looked at histopathology as a prognostic factor indeed tion of the variables are crucial steps that condition the failed to show any difference between the follicular and non- modeling process [3]. In the Cox analysis, the maximum likelihood of the analysis is given and its magnitude shows follicular varieties of low grade lymphoma. Dr Coiffier then goes on the stress the biological hetero- whether the results reflect reality and if all the independent geneity of follicular lymphoma which is exactly the point that variables have been included. Leonard and coworkers did we would like to dissect out by examining the clinical char- not give this data. As they did not include true important acteristics. Of course in an ideal world we would all like to be prognostic factors that have been isolated in other analyses, it able to measure the genetic lesions and the oncoprotein is questionable whether their results could be applied to sets expressions in the cells and serum but lacking these data we of patients other than those studied by the Scotland and have to make the maximum use intelligently of such data as Newcastle Lymphoma Group. In order to facilitate comparative studies between groups have been recorded in patients who have sufficient follow-up to provide reliable survival outcomes for prognostic models. and centres there is a need to move toward a uniform apThe clinical features we described undoubtedly are second- proach in staging lymphomas. Such an approach should be ary correlates of the fundamental processes which in time based on a universally agreed-upon prognostic index whose may be revealed. I suppose we should feel apologetic for not reliability and discrimination have been proven but which is measuring LDH which is the fashionable marker of interest also clinically sound and easy to remember, that is, that it but it simply wasn't available in our database and unlike the would spring readily to the mind of the physician upon his major studies quoted in support of using that marker we at examination of the patient and his chart of exams. The Ann least have tested our index on an independent data set of low Arbor staging system for Hodgkin's disease is a good examgrade disease. In this context it is worth noting of course that ple of this definition. The new 'International Index' described our index works very well within any of the given histopathol- for large-cell lymphoma [4] is another. If the 'International ogy groups. So, if for reasons of intellectual purity you wish Index' can be applied with the same effectiveness to other to exclude diffuse low grade lymphoma from our report then types of lymphomas, it will probably be the best candidate the index works equally well for follicular lymphoma of low for a universally accepted prognostic index in lymphomas. grade variety (as we clearly showed in our paper). As for ease of application of the index it seemed to us the B. Coiffier numbers were very straightforward and could be easily ap- Service d'Hematologie, Centre Hospitalier Lyon-Sud, plied by anyone who is numerate. I tested the ease of use on 69310 Pierre-Benite, France 1. Talbot RW, Irvine B, Jass JR et al. Bone metastases in carcinoma of the rectum: A clinical and pathological review. Eur J Surg Oncol 1989; 15:449-52. 2. Buckley N, Brown P. Metastatic tumors in the hand from adenocarcinoma of the colon. Dis Colon Rectum 1987; 30: 141-3. 3. Hodges FJ. Pathology of the skull. In Taveras JM, Ferruci JT: Radiology: Diagnosis-imaging intervention. 1st ed. 1986, JB Lippincott Co., vol 3, Ch 3, pp. 18-20. 4. Bresalier RS, Karlin D. Meningeal metastases from rectal carcinoma with elevated cerebrospinal fluid carcinoembryonic antigen. Dis Colon Rectum 1979; 22: 216-7.
Letters to the editor Colorectal cancer presenting as isolated skull metastasis Bone metastases are very common in some neoplasms, but are clinically uncommon in colorectal cancer, although they have been reported in 20% of postmortems on patients treated for colorectal neoplasms [1|. We report a very unusual case of a patient suffering a VI cranial nerve palsy secondary to a sphenoidal bone deposit as initial manifestation of a colorectal rumour.
Case report
pain without rebound tenderness on palpation. A barium enema showed a perforated left colonic tumour, and exteriorization of the perforation and peritoneal lavage were performed. Adenocarcinoma was determined upon microscopical examination of the descending colon specimen (Fig. 2). Immunochemistry showed an intense and diffuse immunoreactivity when CEA was added. Lymph nodes were positive for malignant cells. Intraoperatory survey of the liver showed diffuse infiltration by metastases. The patient developed widespread pathological fractures and hypercalcemia. He suffered continuously from severe pain, followed by loss of appetite and lethargy, and died three months after presentation.
A 55-yr-old male was admitted to the hospital because of sudden development of diplopia. He had no evidence of weight loss, change in bowel habits, melena, or flank or abdominal pain. Physical examination showed a VI left cranial nerve palsy (paralysis of abduction and a convergent strabismus) but no other neurologic deficit. The remaining examinations furnished no additional information. A computed tomogram of the brain showed a lytic lesion on the body of the sphenoid bone (Fig. 1A) that was enhanced by intravenous contrast (Fig. IB). There were no brain lesions or ventricular enlargements.
Fig. 2. A malignant gland composed of columnar cells in a patient with colonic adenocarcinoma.
Discussion In a recent report on patients with colorectal carcinoma, bone metastases were diagnosed one to 100 months (median 21) after surgical treatment of the primary tumor. Most patients presented with bone pain. Lumbar spine was the most frequent site of metastases (62%), while skull lesions were Fig. I. (A) Non-enhanced CT scan. A lytic lesion (arrows) affecting found in 6% of the cases. Radiological findings were variable, the body of the sphenoid bone and clivus; (B) Contrast-enhanced with lytic lesions being the most common. Communication CT scan. The same lesion showing irregular enhancement. between the veins of the lower rectum, pelvis and vertebral system may account for the frequency of metastasis to the lumbar spine [1, 2]. The results of blood analyses of hemoglobin, serum calNeoplastic involvement of the skull is most frequently by cium, alkaline phosphatase, SGOT, SGPT, total bilirubin, metastasis or invasion from adjacent neoplasms, followed by albumin and total protein were within normal range. Serum myeloma and lymphoma, all of them with a radiological carcinoembryonic antigen (CEA) was 1870 U/L. The chest appearance of multiple lucent or lytic lesions. Infrequently, x-ray film revealed clear lung fields. No evidence of metas- metastases present as solitary lesions in skull base, and diftases was found on liver sonography. Results of conventional ferential diagnosis with plasmacytoma and chordoma must radiography of the axial skeleton were normal. A bone scan be considered in adult patients [3|. showed widespread metastases. Microscopical examination It should be noted that neurological symptoms in patients of bone marrow yielded negative results. The cerebrospinal with metastatic colorectal cancer are rare. Indeed, in the literature reviewed, only three patients treated for colorectal fluid examination failed to reveal malignant cells. During his hospital stay the patient presented abdominal cancer showed cranial nerve palsy, but in none were neuro-
322 logical symptoms evident as manifest features of the neoplasm [4].
my 11 and 13-year-old daughters who arrived at the right scores without even a pocket calculator!
J. L. Rodriguez-Garcia, J. Martinez-San-Millan, C. Cuesta, J. Perales, G. Fraile & M. Serrano From the Departments of Internal Medicine, Radiology and Pathology, Hospital Ramon y Cajal, Carretera de Colmenarkm. 9,100 28034 Madrid, Spain
R. C. F. Leonard Department of Clinical Oncology, Western General Hospital, Edinburgh, EH4 2XU, U.K.
References
The above letter was referred to the author, who responds as follows:
Dr. Leonard and his coworkers address several points in their letter, the first of which concerns the methods they used to describe and validate their prognostic index for low-grade lymphomas [1]. I agree that dividing their patients into two groups learning and test subgroups, permits a prospective validation of the results, which has rarely been done in early analyses of this type. The test group comprises all patients from one center that had been excluded from the first analysis. While this permits validation of results by an independent procedure, the best method for doing this would have been to randomly allocate patients to the learning or test subgroups or to test the described index on an independent set of data [2]. The main point of their letter concerns the variables to be Prognosis in low grade lymphoma included in such an analysis of prognostic factors in order to I would like to reply, on behalf of my co-authors, to Professor define a prognostic Index useful to others. The primary reaCoifEer's generally helpful leading article which accompanied son for doing such analyses is to propose a means for stratiour paper in volume 2 of Annals of Oncology, pp. 655-662. fying patients before treatment into subgroups of known He stresses the common features amongst the various grades prognosis and then to propose the best available treatment of follicular lymphomas in contrast to diffuse low grade lym- for each of these subgroups. Only explanatory variables studied at the time of patients phoma However he fails to mention the one feature which strikes the physician managing patients with various types of accrual should be included in such analyses, and if a variable low grade lymphoma, which is the long duration of the was not included in the study design it is too late to have it natural history, i.e. the clinical aggressiveness. Our analysis measured at the time of analysis. This selection and definiwhich looked at histopathology as a prognostic factor indeed tion of the variables are crucial steps that condition the failed to show any difference between the follicular and non- modeling process [3]. In the Cox analysis, the maximum likelihood of the analysis is given and its magnitude shows follicular varieties of low grade lymphoma. Dr Coiffier then goes on the stress the biological hetero- whether the results reflect reality and if all the independent geneity of follicular lymphoma which is exactly the point that variables have been included. Leonard and coworkers did we would like to dissect out by examining the clinical char- not give this data. As they did not include true important acteristics. Of course in an ideal world we would all like to be prognostic factors that have been isolated in other analyses, it able to measure the genetic lesions and the oncoprotein is questionable whether their results could be applied to sets expressions in the cells and serum but lacking these data we of patients other than those studied by the Scotland and have to make the maximum use intelligently of such data as Newcastle Lymphoma Group. In order to facilitate comparative studies between groups have been recorded in patients who have sufficient follow-up to provide reliable survival outcomes for prognostic models. and centres there is a need to move toward a uniform apThe clinical features we described undoubtedly are second- proach in staging lymphomas. Such an approach should be ary correlates of the fundamental processes which in time based on a universally agreed-upon prognostic index whose may be revealed. I suppose we should feel apologetic for not reliability and discrimination have been proven but which is measuring LDH which is the fashionable marker of interest also clinically sound and easy to remember, that is, that it but it simply wasn't available in our database and unlike the would spring readily to the mind of the physician upon his major studies quoted in support of using that marker we at examination of the patient and his chart of exams. The Ann least have tested our index on an independent data set of low Arbor staging system for Hodgkin's disease is a good examgrade disease. In this context it is worth noting of course that ple of this definition. The new 'International Index' described our index works very well within any of the given histopathol- for large-cell lymphoma [4] is another. If the 'International ogy groups. So, if for reasons of intellectual purity you wish Index' can be applied with the same effectiveness to other to exclude diffuse low grade lymphoma from our report then types of lymphomas, it will probably be the best candidate the index works equally well for follicular lymphoma of low for a universally accepted prognostic index in lymphomas. grade variety (as we clearly showed in our paper). As for ease of application of the index it seemed to us the B. Coiffier numbers were very straightforward and could be easily ap- Service d'Hematologie, Centre Hospitalier Lyon-Sud, plied by anyone who is numerate. I tested the ease of use on 69310 Pierre-Benite, France 1. Talbot RW, Irvine B, Jass JR et al. Bone metastases in carcinoma of the rectum: A clinical and pathological review. Eur J Surg Oncol 1989; 15:449-52. 2. Buckley N, Brown P. Metastatic tumors in the hand from adenocarcinoma of the colon. Dis Colon Rectum 1987; 30: 141-3. 3. Hodges FJ. Pathology of the skull. In Taveras JM, Ferruci JT: Radiology: Diagnosis-imaging intervention. 1st ed. 1986, JB Lippincott Co., vol 3, Ch 3, pp. 18-20. 4. Bresalier RS, Karlin D. Meningeal metastases from rectal carcinoma with elevated cerebrospinal fluid carcinoembryonic antigen. Dis Colon Rectum 1979; 22: 216-7.
