- Email: [email protected]
Asymptomatic giant renal oncocytoma presenting with hypertension
CORRESPONDENCE
Asymptomatic giant renal oncocytoma presenting with hypertension Sir, Renal oncocytomas are considered benign neoplasms originating from the distal renal tubules. Before modern imaging techniques were widely available, they were thought to be responsible for approximately 3–7% of all renal neoplasms.1 The recent increase in identification of incidental, asymptomatic, often small renal tumours has increased the representation of oncocytoma to over 14%.2 The absence of symptoms (haemorrhage and pain) in most currently diagnosed renal tumours is believed to be closely related to a small tumour size. However, we present an asymptomatic oncocytoma that represents the largest such tumour described in the literature that has been treated by radical surgical intervention at the time of first presentation. The patient, a male aged 37 years, of normal body mass and with no medical history of note, presented to a local general practitioner for a routine insurance medical examination. He was found to be moderately hypertensive with a large ballotable right-sided abdominal mass. Abdominal ultrasound and contrast computed tomography (CT) showed a large (20 cm) mass above the right kidney (Fig. 1). Serum cortisol, renin and aldosterone levels were normal and urine 24-hour vanilylmandelic acid (VMA) was within the normal range. A right radical nephrectomy was performed and the patient was discharged on day 7 without
723
complications. On follow-up at 3 months the patient’s hypertension had resolved. The renal tumour measured 200 mm in maximal diameter and weighed 3353 g. On section, it was a mahogany colour and a large scar was identified (Fig. 2). The tumour was composed of nests, cords and sheets of brightly eosinophilic cells diagnostic of oncocytoma (Fig. 3) while immunostains for vimentin and cytokeratin 7 (CK7) were negative. Renal oncocytomas represent an increasing percentage of incidentally discovered asymptomatic solid renal masses. It is rare for asymptomatic tumours to achieve diameters greater than 20 cm, even if benign, and the three previously reported ‘giant’ oncocytomas presented clinically with pain or discomfort.3–5 This tumour represents the largest oncocytoma that has been treated on primary presentation and furthermore the patient was asymptomatic. The only reported case of greater dimensions (270 mm) was not initially treated and only after prolonged follow-up and tumour growth was surgical intervention considered.3 Hypertension may complicate renal tumours either as a paraneoplastic event6 or by direct compression of the renal
FIG. 2 Gross section shows a large mahogany coloured tumour with scar (arrow). White scale bar ¼ 4.0 cm.
FIG. 1 Contrast computed tomography (coronal view) showing a large mass above the right kidney.
FIG. 3 The tumour was composed of brightly eosinophilic cells with uniform round nuclei diagnostic of oncocytoma (H&E,6128).
724
CORRESPONDENCE
vasculature. In this case there was no evidence of any ectopic hormonal production and in view of the massive tumour dimensions and complete resolution of the hypertension after surgery, the latter event most likely explains this process. Although there have been reports of nephrotic syndrome associated with oncocytomas,7,8 to our knowledge this is the first case of isolated hypertension in an asymptomatic patient with a large oncocytoma. Differentiating oncocytoma from chromophobe renal cell carcinoma is essential but can be difficult in some cases. They are both thought to be derivatives from distal tubules of the collecting system and show intercalated cells.1 In this case the typical tumour morphology and absence of CK7 staining supports the diagnosis of renal oncocytoma. Siva Sundararajan* Jonathon Dyer* Richard Pemberton*{ Ronald J. Cohen{ *Department of Urology, Sir Charles Gairdner Hospital, Nedlands, {Western Urology, Leederville, and {Uropath Pty Ltd, West Leederville, Western Australia Contact Dr R. J. Cohen. E-mail: [email protected]
1. Kuroda N, Toi M, Hiroi M, et al. Review of renal oncocytoma with focus on clinical and pathobiological aspects. Histol Histopathol 2003; 18: 935–42. 2. Vasudevan A, Davies RJ, Shannon BA, et al. Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy. BJU Int 2006; 97: 946–9. 3. Demos TC, Malone AJ Jr. Computed tomography of a giant renal oncocytoma. J Comp Assist Tomogr 1988; 12: 899–900. 4. Banks KL, Cherullo EE, Novick AC. Giant renal oncocytoma. Urology 2001; 57: 365. 5. Kilic S, Altinok MT, Ipek D, et al. Case report of a giant renal oncocytoma. Int Urol Nephrol 2003; 35: 83–4. 6. Lindop GB, Fleming S. Renin in renal cell carcinoma – an immunocytochemical study using an antibody to pure human renin. J Clin Pathol 1984; 37: 27–31. 7. Forland M, Bannayan GA. Minimal-change lesion nephrotic syndrome with renal oncocytoma. Am J Med 1983; 75: 715–20. 8. Lian M, Mulley W, Kan K, et al. Nephrotic range proteinuria associated with oncocytoma of the native kidney. Nephrol Dial Transplant 2004; 19: 482–5.
DOI: 10.1080/00313020802436865
Fulminant haemophagocytic syndrome Sir, In 1979, Risdall et al. first described a syndrome in patients with immmunosuppression and virus infection, characterised by hepatosplenomegaly, abnormal liver function, fever, and pancytopenia. Lymphadenopathy, pulmonary infiltrate and skin rash were also present. Examination of the tissues from those patients showed marked histiocytic hyperplasia with phagocytosis of erythrocytes and other cellular elements. The histiocytes were cytologically benign and were seen scattered throughout the reticuloendothelial system. This syndrome was initially labelled as ‘virus associated haemophagocytic syndrome (HPS)’.1 Similar
Pathology (2008), 40(7), December
cases of HPS were subsequently reported in patients with fungal, parasitic and bacterial infections;2 thus, the term ‘infection associated HPS’ was applied.3 Later, HPS with similar features and pathogenesis was reported in patients with lymphomas and leukaemias, most often of T-cell type.4 Aetiologically, HPS is a disorder of inappropriate macrophage activation related to subtle genetic and immunological defects.5 The exact nature of the immune defects is poorly understood, but both cellular and humoural immunity seems to be affected. A defect of the immunoregulatory T cell which results in the overproduction of a group of T-cell cytokines (IL-1, IL-6 and TNF) leading to histiocytic proliferation was strongly proposed.6 Fulminant HPS is an aggressive and often fatal disorder, often affecting children. It has features similar to HPS but in addition the patients have splenomegaly, multiple organ failure, coagulopathy and phagocytosis of blood elements leading to severe cytopenias.7 We report a seasonal clustering (within a 2-month period during summer time in the Asseer region of Saudi Arabia) of three patients with severe constitutional symptoms who presented to the Department of Hematology of Asseer Central Hospital (July–August 2002). Full history, clinical examination and complete laboratory investigations were performed. All of the patients had fever, hepatosplenomegaly, dyshaemopoiesis and histiocytosis with haemophagocytosis. Although jaundice was not a presenting symptom, later on two patients developed deep jaundice. The clinicopathological and haematological features were corroborated and the diagnosis of fulminant HPS was established. This fulminant HPS was associated with cytomegalovirus infection, lymphoma and hepatitis, one case each. Despite intensive supportive therapy, the patients died shortly after admission. A summary of the clinical and laboratory findings is presented in Tables 1 and 2 and Fig. 1. The term ‘haemophagocytosis’ describes the pathological finding of activated macrophages engulfing erythrocytes, leukocytes, platelets and their precursors. Here we report three cases of fulminant HPS. Their clinicopathological and haematological features concur with the previous studies.7 The seasonal clustering of these cases (July–August, summer) is in line with some previous investigations.4 In our series, the diagnosis of HPS was established based on the following criteria: (1) undiagnosed fever (4388C) for seven or more days; (2) unexplained cytopenias affecting at least two cell lines; (3) bone marrow showing mature histiocytes more than 3% with prominent haemophagocytosis of two or more cell lines; (4) splenomegaly. Other supporting features were abnormal liver functions, coagulopathy, skin rashes, jaundice, and lymphadenopathy.7 Several cases of fulminant HPS have been reported from Asia where viral infection was an associated aetiology.8 Other infectious agents associated with HPS included Epstein–Barr virus, adenovirus, Dengue virus, herpes simplex virus, parvovirus B19, and other bacterial, fungal, rickettsial and parasitic pathogens.9 In our study, inciting viral infection (cytomegalovirus and hepatitis) was seen in two patients (Cases 1 and 3), supporting the notion that viral aetiology may share the development of HPS.2 In agreement with previous studies, a secondary infection by Pseudomonas aeroginosa was seen in one patient.10 Interestingly, the clinical presentation of fulminant HPS may
Asymptomatic giant renal oncocytoma presenting with hypertension Sir, Renal oncocytomas are considered benign neoplasms originating from the distal renal tubules. Before modern imaging techniques were widely available, they were thought to be responsible for approximately 3–7% of all renal neoplasms.1 The recent increase in identification of incidental, asymptomatic, often small renal tumours has increased the representation of oncocytoma to over 14%.2 The absence of symptoms (haemorrhage and pain) in most currently diagnosed renal tumours is believed to be closely related to a small tumour size. However, we present an asymptomatic oncocytoma that represents the largest such tumour described in the literature that has been treated by radical surgical intervention at the time of first presentation. The patient, a male aged 37 years, of normal body mass and with no medical history of note, presented to a local general practitioner for a routine insurance medical examination. He was found to be moderately hypertensive with a large ballotable right-sided abdominal mass. Abdominal ultrasound and contrast computed tomography (CT) showed a large (20 cm) mass above the right kidney (Fig. 1). Serum cortisol, renin and aldosterone levels were normal and urine 24-hour vanilylmandelic acid (VMA) was within the normal range. A right radical nephrectomy was performed and the patient was discharged on day 7 without
723
complications. On follow-up at 3 months the patient’s hypertension had resolved. The renal tumour measured 200 mm in maximal diameter and weighed 3353 g. On section, it was a mahogany colour and a large scar was identified (Fig. 2). The tumour was composed of nests, cords and sheets of brightly eosinophilic cells diagnostic of oncocytoma (Fig. 3) while immunostains for vimentin and cytokeratin 7 (CK7) were negative. Renal oncocytomas represent an increasing percentage of incidentally discovered asymptomatic solid renal masses. It is rare for asymptomatic tumours to achieve diameters greater than 20 cm, even if benign, and the three previously reported ‘giant’ oncocytomas presented clinically with pain or discomfort.3–5 This tumour represents the largest oncocytoma that has been treated on primary presentation and furthermore the patient was asymptomatic. The only reported case of greater dimensions (270 mm) was not initially treated and only after prolonged follow-up and tumour growth was surgical intervention considered.3 Hypertension may complicate renal tumours either as a paraneoplastic event6 or by direct compression of the renal
FIG. 2 Gross section shows a large mahogany coloured tumour with scar (arrow). White scale bar ¼ 4.0 cm.
FIG. 1 Contrast computed tomography (coronal view) showing a large mass above the right kidney.
FIG. 3 The tumour was composed of brightly eosinophilic cells with uniform round nuclei diagnostic of oncocytoma (H&E,6128).
724
CORRESPONDENCE
vasculature. In this case there was no evidence of any ectopic hormonal production and in view of the massive tumour dimensions and complete resolution of the hypertension after surgery, the latter event most likely explains this process. Although there have been reports of nephrotic syndrome associated with oncocytomas,7,8 to our knowledge this is the first case of isolated hypertension in an asymptomatic patient with a large oncocytoma. Differentiating oncocytoma from chromophobe renal cell carcinoma is essential but can be difficult in some cases. They are both thought to be derivatives from distal tubules of the collecting system and show intercalated cells.1 In this case the typical tumour morphology and absence of CK7 staining supports the diagnosis of renal oncocytoma. Siva Sundararajan* Jonathon Dyer* Richard Pemberton*{ Ronald J. Cohen{ *Department of Urology, Sir Charles Gairdner Hospital, Nedlands, {Western Urology, Leederville, and {Uropath Pty Ltd, West Leederville, Western Australia Contact Dr R. J. Cohen. E-mail: [email protected]
1. Kuroda N, Toi M, Hiroi M, et al. Review of renal oncocytoma with focus on clinical and pathobiological aspects. Histol Histopathol 2003; 18: 935–42. 2. Vasudevan A, Davies RJ, Shannon BA, et al. Incidental renal tumours: the frequency of benign lesions and the role of preoperative core biopsy. BJU Int 2006; 97: 946–9. 3. Demos TC, Malone AJ Jr. Computed tomography of a giant renal oncocytoma. J Comp Assist Tomogr 1988; 12: 899–900. 4. Banks KL, Cherullo EE, Novick AC. Giant renal oncocytoma. Urology 2001; 57: 365. 5. Kilic S, Altinok MT, Ipek D, et al. Case report of a giant renal oncocytoma. Int Urol Nephrol 2003; 35: 83–4. 6. Lindop GB, Fleming S. Renin in renal cell carcinoma – an immunocytochemical study using an antibody to pure human renin. J Clin Pathol 1984; 37: 27–31. 7. Forland M, Bannayan GA. Minimal-change lesion nephrotic syndrome with renal oncocytoma. Am J Med 1983; 75: 715–20. 8. Lian M, Mulley W, Kan K, et al. Nephrotic range proteinuria associated with oncocytoma of the native kidney. Nephrol Dial Transplant 2004; 19: 482–5.
DOI: 10.1080/00313020802436865
Fulminant haemophagocytic syndrome Sir, In 1979, Risdall et al. first described a syndrome in patients with immmunosuppression and virus infection, characterised by hepatosplenomegaly, abnormal liver function, fever, and pancytopenia. Lymphadenopathy, pulmonary infiltrate and skin rash were also present. Examination of the tissues from those patients showed marked histiocytic hyperplasia with phagocytosis of erythrocytes and other cellular elements. The histiocytes were cytologically benign and were seen scattered throughout the reticuloendothelial system. This syndrome was initially labelled as ‘virus associated haemophagocytic syndrome (HPS)’.1 Similar
Pathology (2008), 40(7), December
cases of HPS were subsequently reported in patients with fungal, parasitic and bacterial infections;2 thus, the term ‘infection associated HPS’ was applied.3 Later, HPS with similar features and pathogenesis was reported in patients with lymphomas and leukaemias, most often of T-cell type.4 Aetiologically, HPS is a disorder of inappropriate macrophage activation related to subtle genetic and immunological defects.5 The exact nature of the immune defects is poorly understood, but both cellular and humoural immunity seems to be affected. A defect of the immunoregulatory T cell which results in the overproduction of a group of T-cell cytokines (IL-1, IL-6 and TNF) leading to histiocytic proliferation was strongly proposed.6 Fulminant HPS is an aggressive and often fatal disorder, often affecting children. It has features similar to HPS but in addition the patients have splenomegaly, multiple organ failure, coagulopathy and phagocytosis of blood elements leading to severe cytopenias.7 We report a seasonal clustering (within a 2-month period during summer time in the Asseer region of Saudi Arabia) of three patients with severe constitutional symptoms who presented to the Department of Hematology of Asseer Central Hospital (July–August 2002). Full history, clinical examination and complete laboratory investigations were performed. All of the patients had fever, hepatosplenomegaly, dyshaemopoiesis and histiocytosis with haemophagocytosis. Although jaundice was not a presenting symptom, later on two patients developed deep jaundice. The clinicopathological and haematological features were corroborated and the diagnosis of fulminant HPS was established. This fulminant HPS was associated with cytomegalovirus infection, lymphoma and hepatitis, one case each. Despite intensive supportive therapy, the patients died shortly after admission. A summary of the clinical and laboratory findings is presented in Tables 1 and 2 and Fig. 1. The term ‘haemophagocytosis’ describes the pathological finding of activated macrophages engulfing erythrocytes, leukocytes, platelets and their precursors. Here we report three cases of fulminant HPS. Their clinicopathological and haematological features concur with the previous studies.7 The seasonal clustering of these cases (July–August, summer) is in line with some previous investigations.4 In our series, the diagnosis of HPS was established based on the following criteria: (1) undiagnosed fever (4388C) for seven or more days; (2) unexplained cytopenias affecting at least two cell lines; (3) bone marrow showing mature histiocytes more than 3% with prominent haemophagocytosis of two or more cell lines; (4) splenomegaly. Other supporting features were abnormal liver functions, coagulopathy, skin rashes, jaundice, and lymphadenopathy.7 Several cases of fulminant HPS have been reported from Asia where viral infection was an associated aetiology.8 Other infectious agents associated with HPS included Epstein–Barr virus, adenovirus, Dengue virus, herpes simplex virus, parvovirus B19, and other bacterial, fungal, rickettsial and parasitic pathogens.9 In our study, inciting viral infection (cytomegalovirus and hepatitis) was seen in two patients (Cases 1 and 3), supporting the notion that viral aetiology may share the development of HPS.2 In agreement with previous studies, a secondary infection by Pseudomonas aeroginosa was seen in one patient.10 Interestingly, the clinical presentation of fulminant HPS may