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Early onset of prostate cancer in a patient with common variable immunodeficiency
Clinical Oncology (2004) 16: 502–504
Correspondence doi:10.1016/j.clon.2004.06.026
Early Onset of Prostate Cancer in a Patient with Common Variable Immunodeficiency Sir d Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, which may be characterised by development of recurrent infections, autoimmune disorders and systemic granulomatosis. Patients with CVID have been reported to have a higher incidence of lymphoproliferative and gastrointestinal malignancies [1,2]. An unusual case of a young man who was diagnosed with CVID and subsequently developed adenocarcinoma of the prostate is reported. A 39-year-old white man presented with productive cough, fatigue and mild fever for 5 days. He had a history of recurrent attacks of sinusitis, bronchitis and pneumonia since childhood. He had undergone a paranasal sinus operation 9 years ago. There was no history of malignancy in his family. Chest radiograph and laboratory examinations were normal except for a decreased serum globulin level of 1.6 g/dl (normal [N]: 2.0–3.5 g/dl). He had no autoantibodies, and was seronegative for viral hepatitis and human immunodeficiency viruses (HIV-1, HIV-2). Serum quantitative immunoglobulins showed marked hypogammaglobulinaemia (immunoglobulin A [IgA]: 9 mg/dl [N: 68–378 mg/dl]; IgM: 13 mg/dl [N: 60– 263 mg/dl]; IgG: 62 mg/dl [N: 694–1618 mg/dl]). Serum albumin 58.6%, a-1 globulin 7.7%, a-2 globulin 17.3%, b-globulin 11.6%, and g-globulin 6.8% levels were detected with protein electrophoresis. Immunocytochemical analysis of peripheral blood showed normal T- and B-lymphocyte subsets (CD3: 82.3%, CD4: 46.9%, CD8: 34%, CD19: 11.7%, CD20: 13.6%, CD5: 69%, CD16/CD56: 10.5%). Bone-marrow aspiration and pulmonary function tests were normal. He was started on 400 mg/kg of intravenous immunoglobulin per month. Three months later, he developed obstructive urinary symptoms. Digital rectal examination revealed an enlarged prostate gland with hard irregular areas. Serum prostate-specific antigen (PSA) level was 17.6 ng/ml. Ultrasound-guided prostate biopsy showed adenocarcinoma. He was staged T2b N0 M0 (Gleason score 6) after bone scan and computed tomography of the abdomen and chest. He underwent nerve-sparing radical retropubic prostatectomy. Intraoperative pathology showed organconfined adenocarcinoma of one lobe of the prostate gland. At 6-month follow-up, his PSA level was 2.6. Pathogenesis of CVID is an undefined immune dysregulation due to B-cell activation abnormality that results in hypogammaglobulinaemia, although various T-cell defects have also been reported [1]. Most CVID patients have normal numbers of mature B-cells, which are unable to secrete immunoglobulins due to defective interaction between T- and B-cells. The risk of developing cancers in CVID patients has been shown to increase by 13-fold [1] and six-fold [2] in two studies, with higher incidence of lymphomas and gastric cancers. A recent report also describes early onset of breast cancer in two female CVID patients [3]. Possible causes of carcinogenesis in CVID may be due to interaction between infection and altered immunity, although increased radiosensitivity to chromosomal damage in circulating lymphocytes has been shown in CVID patients [4]. Prostate cancer has been associated with viruses like herpesvirus type 2, cytomegalovirus, human papillomavirus, and recently human herpesvirus-8 [5]. Hence, altered immune function in CVID and the potential viral cause of prostate cancer could be associated. Further biological studies are needed to clarify the nature of the relationship. The co-occurrence of early onset prostate cancer (incidence in age !40 years: 0.7/100 000) and CVID (incidence: 1/25 000) is rare and ill defined.
0936-6555/04/070502C03 $35.00/0
As CVID patients have a higher risk of developing cancers, early screening and surveillance for cancers should be considered in these patients. I. MOHAMMED
Department of Internal Medicine, Mercy Hospital of Pittsburgh, Pittsburgh, PA, USA
References 1 Cunningham-Rundles C, Siegal FP, Cunningham-Rundles S, Lieberman P. Incidence of cancer in 98 patients with common varied immunodeficiency. J Clin Immunol 1987;7:294–299. 2 Kinlen LJ, Webster AD, Bird AG, et al. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet 1985;1:263–266. 3 Mehta AC, Faber-Langendoen K, Duggan DB. Common variable immunodeficiency and breast cancer. Cancer Invest 2004;22:93–96. 4 Vorechovsky I, Scott D, Haeney MR, Webster DA. Chromosomal radiosensitivity in common variable immune deficiency. Mutat Res 1993;290:255–264. 5 Hoffman LJ, Bunker CH, Pellett PE, et al. Elevated seroprevalence of human herpesvirus 8 among men with prostate cancer. J Infect Dis 2004; 189:15–20.
doi:10.1016/j.clon.2004.06.025
Distant Cutaneous Metastasis after Laparoscopic Cholecystectomy in a Case of Unsuspected Gallbladder Cancer Sir d We would like to report a rare occurrence of distant cutaneous metastasis in an unsuspected case of gallbladder cancer after laparoscopic cholecystectomy. A 47-year-old woman presented at our institute with complaints of a lump and epigastric pain after a laparoscopic cholecystectomy, which was carried out 8 months previously at a private hospital for chronic cholecystitis and cholelithiasis. Operative details and findings of the procedure were not available. Histopathology of the resected specimen was reported as chronic cholecystitis. The firm, non-tender lump was present at the laparoscopy site and contrast-enhanced computed tomography (CECT) showed a 3 ! 3 ! 2 cm3 mass in the anterior abdominal wall (Fig. 1). Fine-needle aspiration cytology (FNAC) was reported as metastatic adenocarcinoma. Histopathological review of the initial slides from the resected gallbladder specimen confirmed foci of neoplastic changes in the wall of the gallbladder with transmural infiltration. The patient underwent excision of the parietal wall tumour followed by postoperative radiotherapy to the gallbladder and tumour bed (50 Gy in 25 fractions for 5 weeks). Within 1 month of completion of radiotherapy, just outside the radiation port, the patient developed a hard, tender subcutaneous nodule, which was positive for adenocarcinoma on FNAC. This nodule was excised and the tumour bed implanted intraoperatively with flexible catheters in two planes to deliver 30 Gy in six fractions by highdose-rate interstitial brachytherapy. After brachytherapy, the patient was started on a combination of 5-fluorouracil, doxorubicin and mitomycin-C (FAM). By the time the patient was due for her next cycle of chemotherapy, she developed fresh crops of multiple firm, non-tender, subcutaneous nodules ranging from 2–4 cm in diameter over the anterior
Ó 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Correspondence doi:10.1016/j.clon.2004.06.026
Early Onset of Prostate Cancer in a Patient with Common Variable Immunodeficiency Sir d Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, which may be characterised by development of recurrent infections, autoimmune disorders and systemic granulomatosis. Patients with CVID have been reported to have a higher incidence of lymphoproliferative and gastrointestinal malignancies [1,2]. An unusual case of a young man who was diagnosed with CVID and subsequently developed adenocarcinoma of the prostate is reported. A 39-year-old white man presented with productive cough, fatigue and mild fever for 5 days. He had a history of recurrent attacks of sinusitis, bronchitis and pneumonia since childhood. He had undergone a paranasal sinus operation 9 years ago. There was no history of malignancy in his family. Chest radiograph and laboratory examinations were normal except for a decreased serum globulin level of 1.6 g/dl (normal [N]: 2.0–3.5 g/dl). He had no autoantibodies, and was seronegative for viral hepatitis and human immunodeficiency viruses (HIV-1, HIV-2). Serum quantitative immunoglobulins showed marked hypogammaglobulinaemia (immunoglobulin A [IgA]: 9 mg/dl [N: 68–378 mg/dl]; IgM: 13 mg/dl [N: 60– 263 mg/dl]; IgG: 62 mg/dl [N: 694–1618 mg/dl]). Serum albumin 58.6%, a-1 globulin 7.7%, a-2 globulin 17.3%, b-globulin 11.6%, and g-globulin 6.8% levels were detected with protein electrophoresis. Immunocytochemical analysis of peripheral blood showed normal T- and B-lymphocyte subsets (CD3: 82.3%, CD4: 46.9%, CD8: 34%, CD19: 11.7%, CD20: 13.6%, CD5: 69%, CD16/CD56: 10.5%). Bone-marrow aspiration and pulmonary function tests were normal. He was started on 400 mg/kg of intravenous immunoglobulin per month. Three months later, he developed obstructive urinary symptoms. Digital rectal examination revealed an enlarged prostate gland with hard irregular areas. Serum prostate-specific antigen (PSA) level was 17.6 ng/ml. Ultrasound-guided prostate biopsy showed adenocarcinoma. He was staged T2b N0 M0 (Gleason score 6) after bone scan and computed tomography of the abdomen and chest. He underwent nerve-sparing radical retropubic prostatectomy. Intraoperative pathology showed organconfined adenocarcinoma of one lobe of the prostate gland. At 6-month follow-up, his PSA level was 2.6. Pathogenesis of CVID is an undefined immune dysregulation due to B-cell activation abnormality that results in hypogammaglobulinaemia, although various T-cell defects have also been reported [1]. Most CVID patients have normal numbers of mature B-cells, which are unable to secrete immunoglobulins due to defective interaction between T- and B-cells. The risk of developing cancers in CVID patients has been shown to increase by 13-fold [1] and six-fold [2] in two studies, with higher incidence of lymphomas and gastric cancers. A recent report also describes early onset of breast cancer in two female CVID patients [3]. Possible causes of carcinogenesis in CVID may be due to interaction between infection and altered immunity, although increased radiosensitivity to chromosomal damage in circulating lymphocytes has been shown in CVID patients [4]. Prostate cancer has been associated with viruses like herpesvirus type 2, cytomegalovirus, human papillomavirus, and recently human herpesvirus-8 [5]. Hence, altered immune function in CVID and the potential viral cause of prostate cancer could be associated. Further biological studies are needed to clarify the nature of the relationship. The co-occurrence of early onset prostate cancer (incidence in age !40 years: 0.7/100 000) and CVID (incidence: 1/25 000) is rare and ill defined.
0936-6555/04/070502C03 $35.00/0
As CVID patients have a higher risk of developing cancers, early screening and surveillance for cancers should be considered in these patients. I. MOHAMMED
Department of Internal Medicine, Mercy Hospital of Pittsburgh, Pittsburgh, PA, USA
References 1 Cunningham-Rundles C, Siegal FP, Cunningham-Rundles S, Lieberman P. Incidence of cancer in 98 patients with common varied immunodeficiency. J Clin Immunol 1987;7:294–299. 2 Kinlen LJ, Webster AD, Bird AG, et al. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet 1985;1:263–266. 3 Mehta AC, Faber-Langendoen K, Duggan DB. Common variable immunodeficiency and breast cancer. Cancer Invest 2004;22:93–96. 4 Vorechovsky I, Scott D, Haeney MR, Webster DA. Chromosomal radiosensitivity in common variable immune deficiency. Mutat Res 1993;290:255–264. 5 Hoffman LJ, Bunker CH, Pellett PE, et al. Elevated seroprevalence of human herpesvirus 8 among men with prostate cancer. J Infect Dis 2004; 189:15–20.
doi:10.1016/j.clon.2004.06.025
Distant Cutaneous Metastasis after Laparoscopic Cholecystectomy in a Case of Unsuspected Gallbladder Cancer Sir d We would like to report a rare occurrence of distant cutaneous metastasis in an unsuspected case of gallbladder cancer after laparoscopic cholecystectomy. A 47-year-old woman presented at our institute with complaints of a lump and epigastric pain after a laparoscopic cholecystectomy, which was carried out 8 months previously at a private hospital for chronic cholecystitis and cholelithiasis. Operative details and findings of the procedure were not available. Histopathology of the resected specimen was reported as chronic cholecystitis. The firm, non-tender lump was present at the laparoscopy site and contrast-enhanced computed tomography (CECT) showed a 3 ! 3 ! 2 cm3 mass in the anterior abdominal wall (Fig. 1). Fine-needle aspiration cytology (FNAC) was reported as metastatic adenocarcinoma. Histopathological review of the initial slides from the resected gallbladder specimen confirmed foci of neoplastic changes in the wall of the gallbladder with transmural infiltration. The patient underwent excision of the parietal wall tumour followed by postoperative radiotherapy to the gallbladder and tumour bed (50 Gy in 25 fractions for 5 weeks). Within 1 month of completion of radiotherapy, just outside the radiation port, the patient developed a hard, tender subcutaneous nodule, which was positive for adenocarcinoma on FNAC. This nodule was excised and the tumour bed implanted intraoperatively with flexible catheters in two planes to deliver 30 Gy in six fractions by highdose-rate interstitial brachytherapy. After brachytherapy, the patient was started on a combination of 5-fluorouracil, doxorubicin and mitomycin-C (FAM). By the time the patient was due for her next cycle of chemotherapy, she developed fresh crops of multiple firm, non-tender, subcutaneous nodules ranging from 2–4 cm in diameter over the anterior
Ó 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.