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Is second biopsy helpful in the diagnosis of hepatocellular carcinoma with a first negative biopsy?
3688
Letters to the Editor
10. Sorbi D, Boynton J, Lindor KD. The ratio of aspartate to alanine aminotransferase: Potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol 1999;94:1018 –22. Reprint requests and correspondence: Roberto Testa, M.D., Gastroenterology Unit, Department of Internal Medicine (DI.M.I.), Viale Benedetto XV, n6˚, 16132 Genova, Italia. Received Aug. 7, 2000; accepted Aug. 15, 2000.
Is Second Biopsy Helpful in the Diagnosis of Hepatocellular Carcinoma With a First Negative Biopsy? TO THE EDITOR: Focal lesions in the cirrhotic liver, 2 cm or more in diameter, have been long considered to be HCCs (1, 2), however, no guidelines are yet available about what to do when histological findings are negative. In this regard, 1123 cirrhotic patients with liver focal lesions were observed in our centers over a period of 8 yr (1992–99). In 1014 (90.3%), HCC were correctly proven through fine needle biopsy under ultrasound (US) guidance. In 109 patients (9.7%), a first biopsy yielded negative results. Among these patients, 11 were lost at the follow-up; the remaining 98 (67 male, 31 female, mean age 63.6 yr) with a single lesion in postviral cirrhosis, histologically proven, (51 HCV-Ab positive, 28 HBsAg positive, and the remainders positive for both) were stratified into two groups, according to the size of the lesion. Group A was composed of 59 patients (size of the lesion more than 3.5 cm in diameter, mean 4.7 cm) in which the diagnosis was negative, due to lack of diagnostic material, and group B was composed of 39 patients (size of the lesion less than 3.5 cm, mean 2.9 cm) in which the diagnosis was negative, due to absence of neoplastic cells in the specimen. In all these 98 patients, the final diagnosis was obtained either after surgery (46%) or when two or more imaging techniques were positive (colorDoppler, angiography, angio- or spiral-CT, MRI), and the positivity of either alpha-fetoprotein or des-gamma-carboxy-prothrombin was at a significant value (3, 4). Other clinical parameters (increase in size of the lesion, presence of new lesions, and/or portal thrombosis) were also observed. In all cases, both the first and second biopsy (the latter performed within 60 days from the former) were carried out under US guidance with photographic evidence of the correct positioning of the needle using 20 gauge (in 54 cases) or 21 gauge (in 44 cases) needles, with at least two passes for each lesion. A cutting needle for microhistological and cytological samples (Histocut) was used in 46 cases (27 cases of group A, and 19 of group B) and in the remaining 52 cases a Chiba needle for cytological sampling only was employed (32 of group A and 20 of group B). In group A, 14 cytological samples and only 3 microhistological samples, consistent with HCC, were obtained, whereas the remaining 18 cases and 24 microhistological samples
AJG – Vol. 95, No. 12, 2000
again had negative results. Only in 11 cases of group B, the second biopsy yielded cytological material consistent with HCC, with 5 cases positive at microhistology. Overall, a second biopsy corrected a false negative result of the first in only 28/98 (28.5%). Our experience suggests that, in HCC nodules in postviral cirrhosis, a second biopsy, after a first negative histological examination, is unlikely to yield a diagnosis. This seems true regardless of the gauge of the fine needle used, even if the noncutting needle for cytological sampling seems to be better than microhistological one, and regardless of the size of the lesions. In HCCs of greater size, this could be due to necrotic areas, in the smaller ones this could be due to a sampling error in a tumor still well differentiated. Because survival in the patients with HCC after percutaneous ablative therapies is comparable with patients who underwent surgery (5), a negative histological result, in particular in lesions smaller than 3.5 cm (all the present therapeutic options are available) (6), should not contraindicate these techniques. This is true especially because these techniques can be used successfully and with few complications and also in unresectable HCCs. E. Brunetti, M.D. R. Bruno, M.D. A. Marangio, M.D. F. G. Crippa, M.D. C. Filice, M.D. Divisione di Malattie Infettive e Tropicali IRCCS Policlinico S. Matteo, Universita` di Pavia Pavia, Italy E. Caturelli, M.D. Divisione di Gastroenterologia Ospedale “Casa Sollievo della Sofferenza” S. Giovanni Rotondo (FG) Pavia, Italy
REFERENCES 1. Di Bisceglie A, Rustgi V, Hoofnagle J, et al. NIH conference on hepatocellular carcinoma. Ann Intern Med 1988;108:390 – 401. 2. Kondo F, Ebara M, Sugiura N, et al. Histological features and clinical course of large regenerative nodules: Evaluation of their precancerous potentiality. Hepatology 1990;12(3):592– 8. 3. Weitz I, Liebman H. Des-gamma-carboxy (Abnormal) prothrombin and Hepatocellular Carcinoma: A critical review. Hepatology 1993;18:990 –7. 4. Cottone N, D’Antoni A. Early detection and serum markers. In: Livraghi T, Makuuchi O, Buscarini L, eds. Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London 1997;67– 8. 5. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: Long term results of percutaneous ethanol injection. Radiology 1995;197:101– 8. 6. Scott Pearson A, Izzo F, Fleming D, et al. Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies. Am J of Surgery 1999;178:592– 8. 7. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of
AJG – December, 2000
unresectable primary and metastatic hepatic malignancies: Results in 123 patients. Annals of Surgery 1999;230(1):1– 8. Reprint requests and correspondence: C. Fı`lice, M.D., Universita` di Pavia, Divisione di Malattie Infettive e Tropicali, IRCCS Policlinico S. Matteo, Via Taramelli 5, 27100 Pavia, Italy. Received June 16, 2000; accepted June 19, 2000.
An Unusual Case of Metastatic Rectal Carcinoma Presenting as Thyroid Nodule TO THE EDITOR: The thyroid gland is known to be a frequent site of metastatic involvement from primary carcinoma of other organs in autopsies, though it is uncommon antemortem in clinical practice. Kidney, skin, breast, lung, head and neck, genital tract tumors, lymphoma and leukemia, and sarcomas may be the primary malignant lesions that metastasize or involve the thyroid gland (1). Gastrointestinal system malignancies metastasize to the thyroid gland less frequently and are the rare causes of solitary cold nodules in the thyroid (2). Here, we present a patient having metastatic rectal carcinoma presenting as thyroid nodule. A 69-yr-old woman was admitted to the hospital with diffuse bone pain for the last 4 months. She had fatigue and 5 kg weight loss for 3 months. She did not have any complaints of constipation, gastrointestinal bleeding, or tenesmus. Physical examination showed bilateral 1 ⫻ 1 cm mobile, firm 2–3 inguinal lymphadenopathies and a firm, mobile, nontender nodule located in the right thyroid lobe. Her hematological and biochemical tests signified hemoglobin about 10 g/dl, erythrocyte sedimentation rate 80 mm/hr and bone alkaline phosphatase five times higher than normal. Other hematological and biochemical parameters were within normal limits. Bone scanning showed multiple metastatic osteoblastic bone lesions. The urine and serum protein electrophoresis and thyroid function tests were within normal limits. Thorax computed tomography revealed metastatic nodular lesions in lung parenchyma.The abdominal ultrasonography was normal. The thyroid ultrasonography revealed a 18 ⫻ 18 mm solid nodule in the right thyroid lobe and a 16 ⫻ 15 mm calcified nodule in the left thyroid lobe. A hypoactive nodule in the right thyroid lobe and hyperactive one in the left thyroid lobe was demonstrated by thyroid scan with Tc 99m Pertechnetate. Fine needle aspiration (FNA) of the nodule in the right thyroid gland was performed. Cytopathological findings were interpreted as metastatic adenocarcinoma and the gastrointestinal system was favored as the most probable site for the primary tumor. The biopsy from the inguinal lymph node and bone marrow signified mucin-positive adenocarcinoma cells. Occult blood test for stool was positive. Rectosigmoidoscopy was performed and a polipoid lesion in the rectum at the fifth centimeter from anal sphincter was discovered. Rectal polyp
Letters to the Editor
3689
biopsy was diagnosed as mucinous adenocarcinoma. The patient was staged as Dukes D. Chemotherapy regimen with 5-fluorouracil and folinic acid was initiated. Colorectal carcinoma rarely metastasizes to lungs, bone, brain, or other organs such as the thyroid without previously spreading to the liver. A major exception to this rule occurs in patients having primary tumors in the distal rectum as in our patient from which tumor cells may spread through paravertebral venous plexus escaping portal venous system and thereby reaching those organs without hepatic involvement. Owing to its rich vascular supply, the thyroid is a common site of secondary or metastatic cancers from primary tumors found elsewhere. The majority of metastatic neoplasms in the thyroid are found only at autopsy, in about 9% of patients who die of cancer (3). Most of metastases to the thyroid gland originate from renal, skin (malignant melanoma), breast, lung, head and neck, lymphoma and leukemia, gastrointestinal tract, genital tract, and sarcomas (1). Reports of colorectal metastases to the thyroid gland that have been diagnosed antemortem are infrequent. Shimaoka and coworkers reported that colorectal carcinoma metastasized to the thyroid gland accounts for about 4% in a large autopsy series (3). In the differential diagnosis of solitary cold thyroid nodules, metastatic disease should also be considered. Most of the reported rectal carcinoma cases that metastasized to the thyroid gland were diagnosed as having rectal carcinoma before the thyroid gland metastases. Our case is interesting for the fact that the diagnosis of primary lesion was made only after the initial finding of a thyroid gland metastasis. Seyfettin Ko¨klu¨, M.D. I˙brahim Barısta, M.D. Mustafa Kadri Altundag˘, M.D. Salih Aksu, M.D. Pınar Fırat, M.D. Hacettepe Medical Faculty Department of Internal Medicine Hacettepe University Institute of Oncology Hacettepe Medical Faculty Department of Pathology Ankara, Turkey
REFERENCES 1. Mesko TW, Friedman J, Sendzischew H, et al. Rectal carcinoma metastatic to thyroid gland. J Laryngol Otol 1996;110: 192–5. 2. Nachtigal D, Dharan M, Luboshitzky R, et al. Bilateral secondary mucinous adenocarcinoma of thyroid: Case report. Otolaryngol Head Neck Surg 1992;107:466 – 8. 3. Shimaoka K, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland. Cancer 1962;15:557– 65. Reprint requests and correspondence: Mustafa Kadri Altundag˘, M.D., Hacettepe University, Oncology Institute, Department of Medical Oncology, Sıhhiye, 06100, Ankara, Turkey. Received May 23, 2000; accepted June 6, 2000.
Letters to the Editor
10. Sorbi D, Boynton J, Lindor KD. The ratio of aspartate to alanine aminotransferase: Potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol 1999;94:1018 –22. Reprint requests and correspondence: Roberto Testa, M.D., Gastroenterology Unit, Department of Internal Medicine (DI.M.I.), Viale Benedetto XV, n6˚, 16132 Genova, Italia. Received Aug. 7, 2000; accepted Aug. 15, 2000.
Is Second Biopsy Helpful in the Diagnosis of Hepatocellular Carcinoma With a First Negative Biopsy? TO THE EDITOR: Focal lesions in the cirrhotic liver, 2 cm or more in diameter, have been long considered to be HCCs (1, 2), however, no guidelines are yet available about what to do when histological findings are negative. In this regard, 1123 cirrhotic patients with liver focal lesions were observed in our centers over a period of 8 yr (1992–99). In 1014 (90.3%), HCC were correctly proven through fine needle biopsy under ultrasound (US) guidance. In 109 patients (9.7%), a first biopsy yielded negative results. Among these patients, 11 were lost at the follow-up; the remaining 98 (67 male, 31 female, mean age 63.6 yr) with a single lesion in postviral cirrhosis, histologically proven, (51 HCV-Ab positive, 28 HBsAg positive, and the remainders positive for both) were stratified into two groups, according to the size of the lesion. Group A was composed of 59 patients (size of the lesion more than 3.5 cm in diameter, mean 4.7 cm) in which the diagnosis was negative, due to lack of diagnostic material, and group B was composed of 39 patients (size of the lesion less than 3.5 cm, mean 2.9 cm) in which the diagnosis was negative, due to absence of neoplastic cells in the specimen. In all these 98 patients, the final diagnosis was obtained either after surgery (46%) or when two or more imaging techniques were positive (colorDoppler, angiography, angio- or spiral-CT, MRI), and the positivity of either alpha-fetoprotein or des-gamma-carboxy-prothrombin was at a significant value (3, 4). Other clinical parameters (increase in size of the lesion, presence of new lesions, and/or portal thrombosis) were also observed. In all cases, both the first and second biopsy (the latter performed within 60 days from the former) were carried out under US guidance with photographic evidence of the correct positioning of the needle using 20 gauge (in 54 cases) or 21 gauge (in 44 cases) needles, with at least two passes for each lesion. A cutting needle for microhistological and cytological samples (Histocut) was used in 46 cases (27 cases of group A, and 19 of group B) and in the remaining 52 cases a Chiba needle for cytological sampling only was employed (32 of group A and 20 of group B). In group A, 14 cytological samples and only 3 microhistological samples, consistent with HCC, were obtained, whereas the remaining 18 cases and 24 microhistological samples
AJG – Vol. 95, No. 12, 2000
again had negative results. Only in 11 cases of group B, the second biopsy yielded cytological material consistent with HCC, with 5 cases positive at microhistology. Overall, a second biopsy corrected a false negative result of the first in only 28/98 (28.5%). Our experience suggests that, in HCC nodules in postviral cirrhosis, a second biopsy, after a first negative histological examination, is unlikely to yield a diagnosis. This seems true regardless of the gauge of the fine needle used, even if the noncutting needle for cytological sampling seems to be better than microhistological one, and regardless of the size of the lesions. In HCCs of greater size, this could be due to necrotic areas, in the smaller ones this could be due to a sampling error in a tumor still well differentiated. Because survival in the patients with HCC after percutaneous ablative therapies is comparable with patients who underwent surgery (5), a negative histological result, in particular in lesions smaller than 3.5 cm (all the present therapeutic options are available) (6), should not contraindicate these techniques. This is true especially because these techniques can be used successfully and with few complications and also in unresectable HCCs. E. Brunetti, M.D. R. Bruno, M.D. A. Marangio, M.D. F. G. Crippa, M.D. C. Filice, M.D. Divisione di Malattie Infettive e Tropicali IRCCS Policlinico S. Matteo, Universita` di Pavia Pavia, Italy E. Caturelli, M.D. Divisione di Gastroenterologia Ospedale “Casa Sollievo della Sofferenza” S. Giovanni Rotondo (FG) Pavia, Italy
REFERENCES 1. Di Bisceglie A, Rustgi V, Hoofnagle J, et al. NIH conference on hepatocellular carcinoma. Ann Intern Med 1988;108:390 – 401. 2. Kondo F, Ebara M, Sugiura N, et al. Histological features and clinical course of large regenerative nodules: Evaluation of their precancerous potentiality. Hepatology 1990;12(3):592– 8. 3. Weitz I, Liebman H. Des-gamma-carboxy (Abnormal) prothrombin and Hepatocellular Carcinoma: A critical review. Hepatology 1993;18:990 –7. 4. Cottone N, D’Antoni A. Early detection and serum markers. In: Livraghi T, Makuuchi O, Buscarini L, eds. Diagnosis and treatment of hepatocellular carcinoma. Greenwich Medical Media, London 1997;67– 8. 5. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: Long term results of percutaneous ethanol injection. Radiology 1995;197:101– 8. 6. Scott Pearson A, Izzo F, Fleming D, et al. Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies. Am J of Surgery 1999;178:592– 8. 7. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of
AJG – December, 2000
unresectable primary and metastatic hepatic malignancies: Results in 123 patients. Annals of Surgery 1999;230(1):1– 8. Reprint requests and correspondence: C. Fı`lice, M.D., Universita` di Pavia, Divisione di Malattie Infettive e Tropicali, IRCCS Policlinico S. Matteo, Via Taramelli 5, 27100 Pavia, Italy. Received June 16, 2000; accepted June 19, 2000.
An Unusual Case of Metastatic Rectal Carcinoma Presenting as Thyroid Nodule TO THE EDITOR: The thyroid gland is known to be a frequent site of metastatic involvement from primary carcinoma of other organs in autopsies, though it is uncommon antemortem in clinical practice. Kidney, skin, breast, lung, head and neck, genital tract tumors, lymphoma and leukemia, and sarcomas may be the primary malignant lesions that metastasize or involve the thyroid gland (1). Gastrointestinal system malignancies metastasize to the thyroid gland less frequently and are the rare causes of solitary cold nodules in the thyroid (2). Here, we present a patient having metastatic rectal carcinoma presenting as thyroid nodule. A 69-yr-old woman was admitted to the hospital with diffuse bone pain for the last 4 months. She had fatigue and 5 kg weight loss for 3 months. She did not have any complaints of constipation, gastrointestinal bleeding, or tenesmus. Physical examination showed bilateral 1 ⫻ 1 cm mobile, firm 2–3 inguinal lymphadenopathies and a firm, mobile, nontender nodule located in the right thyroid lobe. Her hematological and biochemical tests signified hemoglobin about 10 g/dl, erythrocyte sedimentation rate 80 mm/hr and bone alkaline phosphatase five times higher than normal. Other hematological and biochemical parameters were within normal limits. Bone scanning showed multiple metastatic osteoblastic bone lesions. The urine and serum protein electrophoresis and thyroid function tests were within normal limits. Thorax computed tomography revealed metastatic nodular lesions in lung parenchyma.The abdominal ultrasonography was normal. The thyroid ultrasonography revealed a 18 ⫻ 18 mm solid nodule in the right thyroid lobe and a 16 ⫻ 15 mm calcified nodule in the left thyroid lobe. A hypoactive nodule in the right thyroid lobe and hyperactive one in the left thyroid lobe was demonstrated by thyroid scan with Tc 99m Pertechnetate. Fine needle aspiration (FNA) of the nodule in the right thyroid gland was performed. Cytopathological findings were interpreted as metastatic adenocarcinoma and the gastrointestinal system was favored as the most probable site for the primary tumor. The biopsy from the inguinal lymph node and bone marrow signified mucin-positive adenocarcinoma cells. Occult blood test for stool was positive. Rectosigmoidoscopy was performed and a polipoid lesion in the rectum at the fifth centimeter from anal sphincter was discovered. Rectal polyp
Letters to the Editor
3689
biopsy was diagnosed as mucinous adenocarcinoma. The patient was staged as Dukes D. Chemotherapy regimen with 5-fluorouracil and folinic acid was initiated. Colorectal carcinoma rarely metastasizes to lungs, bone, brain, or other organs such as the thyroid without previously spreading to the liver. A major exception to this rule occurs in patients having primary tumors in the distal rectum as in our patient from which tumor cells may spread through paravertebral venous plexus escaping portal venous system and thereby reaching those organs without hepatic involvement. Owing to its rich vascular supply, the thyroid is a common site of secondary or metastatic cancers from primary tumors found elsewhere. The majority of metastatic neoplasms in the thyroid are found only at autopsy, in about 9% of patients who die of cancer (3). Most of metastases to the thyroid gland originate from renal, skin (malignant melanoma), breast, lung, head and neck, lymphoma and leukemia, gastrointestinal tract, genital tract, and sarcomas (1). Reports of colorectal metastases to the thyroid gland that have been diagnosed antemortem are infrequent. Shimaoka and coworkers reported that colorectal carcinoma metastasized to the thyroid gland accounts for about 4% in a large autopsy series (3). In the differential diagnosis of solitary cold thyroid nodules, metastatic disease should also be considered. Most of the reported rectal carcinoma cases that metastasized to the thyroid gland were diagnosed as having rectal carcinoma before the thyroid gland metastases. Our case is interesting for the fact that the diagnosis of primary lesion was made only after the initial finding of a thyroid gland metastasis. Seyfettin Ko¨klu¨, M.D. I˙brahim Barısta, M.D. Mustafa Kadri Altundag˘, M.D. Salih Aksu, M.D. Pınar Fırat, M.D. Hacettepe Medical Faculty Department of Internal Medicine Hacettepe University Institute of Oncology Hacettepe Medical Faculty Department of Pathology Ankara, Turkey
REFERENCES 1. Mesko TW, Friedman J, Sendzischew H, et al. Rectal carcinoma metastatic to thyroid gland. J Laryngol Otol 1996;110: 192–5. 2. Nachtigal D, Dharan M, Luboshitzky R, et al. Bilateral secondary mucinous adenocarcinoma of thyroid: Case report. Otolaryngol Head Neck Surg 1992;107:466 – 8. 3. Shimaoka K, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland. Cancer 1962;15:557– 65. Reprint requests and correspondence: Mustafa Kadri Altundag˘, M.D., Hacettepe University, Oncology Institute, Department of Medical Oncology, Sıhhiye, 06100, Ankara, Turkey. Received May 23, 2000; accepted June 6, 2000.