170
Brief reports
References 1. Weeks DA. Beckwith JB, Mierau GW. Luckey DW. Rhabdoid tumor
of kidney. A report of 1 1 1 cases from the National Wilms’ Tumor Study Pathology Center. Am. J. Surg. Pathol. 1989; 13: 439-458. 2. Fletcher CDM, McKee PH. Extrarenal rhabdoid tumour. In: Fletcher CDM. McKee PH, eds. Pathobiology of Soft Tissue Tumours. Edinburgh: Churchill Livingstone. 1990; 308-31 1 . 3. Tsuneyoshi M. Daimaru Y , Hashimoto H. Enjoji M. The existence of rhabdoid cells in specified soft tissue sarcomas. Histopathological.
ultrastructural and immunohistochemical evidence. Virchows Archiv. [Pathol. Anat.] 1987; 411; 509-514. 4, Tsokos M, Kouraklis G. Chandra RS, Bhagavan BS, Triche TI. Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochernical phenotype. Arch. Pathol. Lab. Med. 1989: 113; 115-120. 5. Harris M, Eyden BP. Joglekar VM. Rhabdoid tumour of the bladder: a histological, ultrastructural and irnmunohistochemical study. Histopathology 19 8 7; 1 1 ; 108 3- 1092.
Histopathology 1992, 20, 170-173
BRIEF REPORT
Intraorbital rhabdoid tumour following bilateral retinoblastoma N. W ALFORD, R. DEFERRAI* , R. M.SLATER*, J .F .M.DELEMARRE, K .P .DINGEMANS, M.A.VAN DEN BERGH WEERMAN & P.A.VOUTEJDepartment of Pathological Anatomy, *Institute of Human Genetics and tDepartment of Paediatric Oncology, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands Date of submission 22 February 199 1 Accepted for publication 1 7 July 1991
Keywords: rhabdoid tumour, retinoblastoma, nephroblastoma
Introduction Since their first description in the kidney, primary rhabdoid tumours have been described arising in the brain, thymus, bladder, liver, heart, soft tissues, paravertebral region and the prostate region, as well as a single intraorbital case’. We report a second case of intraorbital rhabdoid tumour, of particular interest as arising in the right orbit of a 3-year-old child previously treated for bilateral retinoblastoma.
Case report The patient, a boy, first presented at the age of 2 months with bilateral retinoblastoma, treated by left-sided enucleation and right-sided radiotherapy (lateral field 4 5 Gy), with apparent cure. Histologically, the tumour was a well-differentiated retinoblastoma with well-formed Flexner rosettes. Address for correspondence: Dr J.F.M.Delemarre. Department of Pathological Anatomy, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
Twenty-seven months after first presentation the patient was seen again with a slowfy progressive exophthalmos on the right side. Investigation showed a retrobulbar mass eroding through the sphenoid bone into the middle cranial fossa. Ophthalmoscopy showed no evidence of recurrence of retinoblastoma, and the optic nerve appeared on CT-scan to be normal. Investigation at this time showed no evidence of tumour elsewhere in the body, and in particular no ultrasonographic or roentgenographic evidence of a primary kidney tumour. The patient was treated with chemotherapy and radiotherapy but failed to respond. He died at home as a result of intracranial tumour progression and autopsy was not performed. PATHOLOGICAL FINDINGS
Biopsy material from the right orbit showed a tumour composed of sheets of non-cohesive cells having abundant eosinophilic cytoplasm and large, often eccentric, nuclei with vesicular, clumped chromatin and single central nucleoli (Figure 1a). Rounded hyaline eosinophilic bodies were frequently seen in the cytoplasm. Immunocytochemical staining demonstrated a population of cells strongly positive for cytokeratin (Figure l c )
Brief reports
171
Figure 1 . Tumour section: a typical rhabdoid features with prominent central nucleoli and occasional intracytoplasmic cytoplasmic hyaline bodies (arrow) positive for b vimentin and c cytokeratin. a H & E. x 3SO. b Vimentin. x 230. c Cytokeratin. x 230.
and a population positive for vimentin (Figure lb). The presence of some weaker, more diffuse staining for neuron-specific enolase and for S-100 protein was also noted. Chromogranin, synaptophysin, glial fibrillary acidic protein and desmin immunostaining was negative. By electronmicroscopy the cells showed abundant intracytoplasmic organelles, specifically mitochondria and smooth and rough endoplasmic reticulum, the latter often dilated, and some lysosomes. Three sorts of intracytoplasmic filaments were seen: in some cells intermediate filaments were arranged in whorls which often incorporated other intracellular organelles and which sometimes occupied the bulk of the extranuclear space; more frequently filaments of similar size were arranged in irregular bundles, often around the nucleus: and there were also structures with the morphological features of tonofibrils. Occasional small neurosecretorytype granules were present. Cell surfaces sometimes showed microvillus-like protrusions and some small intercellular junctions were present. A monolayer culture of the tumour was established and cytogenetic analysis carried out. The tumour was hypotetraploid with a range of between 76 and 95 chromosomes per cell and a mode at 8 7. There were only two normal copies of chromosomes 4 , 1 5 and 18 in each metaphase, and in addition the Y chromosome was missing. The majority of cells also had only two copies of chromosome 1 3 , but two metaphases were found with
Table 1 . Clonal structural variations detected in tumour culture ( 1 2 metaphases)*
der(2)t(2;?)(q11;?) de1(5)(q13) der(5)t(1:5)(q21;q31) der(7)t(5;7)(qlI ;q3 1) de1(9)(q2lq32) der(1 l)t(ll:?)(p13:?) der(1 l)t(5;1l)(q22:q23) der(l2)t(12:?)(q22:?)
1 COPY 1 COPY 1 COPY 2 copies 2 copies 2 copies 2 copies 1 COPY
* excluding chromosome 1.
three copies. No structural changes, however, were found in chromosome 13. Clonal structural variation involved chromosomes 1, 2 , 5 . 9, 11 and 12, some variants being present as two copies, indicating that the tumour had undergone polyploidization during its progression. There were up to seven structurally abnormal copies of chromosome 1 in each metaphase involving breakpoints in regions lp36, l p 3 2 , l q 2 1 and lq23. Other clonal changes are listed in Table 1. Electronmicroscopy was carried out on the cells of the monolayer culture. This showed preservation of the characteristic intracytoplasmic filamentous whorls seen in the original tumour (Figure 2 ) .
172
Brief reports
Figure 2. Electronmicrograph of cell from monolayer culture
showing characteristic intracytoplasmic filamentous whorl. x 10000.
Discussion This tumour meets the morphological, immunocytochemica1 and electronmicroscopic criteria for diagnosis of rhabdoid tumours’. It has recently been suggested2 that many of the reported cases of extrarenal rhabdoid tumours are of diverse origins and would better be designated as ‘pseudo-rhabdoid’; it is not apparent, however, on what criteria the distinction of true and pseudo-rhabdoid tumours can be made. The presence of isolated rhabdoid-like cells has been described in a variety of tumours, usually in adults, and with no apparent worsening of prognosis3. Extrarenal rhabdoid tumours, on the other hand, tend to arise, like the renal variety, in infants or children and pursue the same aggressive clinical course with poor response to therapy4.
A number of possible explanations are entertained for the association of rhabdoid tumour and retinoblastoma in this patient: 1 Since the patient has a genetic predisposition to retinoblastoma it is possible that this tumour is a retinoblastoma which has undergone regressive or metaplastic change to show rhabdoid-like features, conceivably in response to radiation. We consider this unlikely on account of the lack of clinically demonstrable retinal involvement as well as the absence of characteristic changes in chromosome 13. 2 Retinoblastoma is known to be associated with a particularly high incidence of second malignant tumour development, both in the field of radiation and elsewhere5.The second tumour is most commonly an
Brief reports
osteosarcoma, but associations appear to exist also with melanoma, other skin cancers and rhabdomyosarcoma5. Interestingly, the latter association was documented prior to the delineation of rhabdoid tumour as an entity distinct from rhabdomyosarcoma in 198 1.The time gap of 2 7 months in this case would be unusually short for a radiogenic tumour, but is not inconsistent with published cases5. 3 An association has been reported between malignant rhabdoid tumour of the kidney and a variety of primitive neuroepithelial malignancies in the central nervous system, the brain tumour frequently preceding clinically that in the kidneyh. This association remains unexplained. The present case represents the first report of a primary extrarenal rhabdoid tumour and primary neuroepithelial tumour in the same patient: and it is conceivable that the presence of such an association in this case represents an analogous process to that seen with the renal rhabdoid tumours.
173
References 1. Rootman J, Damji KF. Dimmick JE. Malignant rhabdoid tumour of the orbit. Ophthalmology 1989: 96; 1650-1654. 2. Mierau GW. Weeks DA, Beckwith ]B. Anaplastic Wilms' tumor and other clinically aggressive childhood renal neoplasms: ultrastructural and immunocytochemical features. Ultrastruct. Pathol. 1989: 13; 225-248. 3 . Tsuneyoshi M. Daimaru Y . Hashimoto H. Enjoji M. The existence of rhabdoid cells in specified soft tissue sarcomas: histopathological. ultrastructural and immunohistochemical evidence. Virchows Archiv. [Pathol. Anat.] 1987: 411; 509-514. 4. Sotelo-Avila C. Gonzales-Crussi F. Demello D et al. Renal and extrarenal rhabdoid tumors in children: a clinicopathological study of 1 4 patients. Semin. Diag. Pathol. 1986: 3: 151-163. 5. Meadows AT, D'Angio GJ. Mike V et al. Patterns of second malignant neoplasms in children. Cancer 1977; 40: 1903-1 91 I . 6 . Bonnin JM, Rubinstein LJ. Palmer NF, Beckwith JB. The association of embryonal tumors originating in the kidney and in the brain. A report of seven cases. Cancer 1984: 54; 2137-2146.
Acknowledgements The work of Ms Deferrai was funded in part by an EEC grant.
Histopathology 1992, 20, 173-1 76
BRIEF REPORT
Renal interstitial foam cells are macrophages M.FRANC0, F-SCHMITT, W.A.REJAIL1, R.M.VIER0 & C.E.BACCHI Department of Pathology, School of Medicine, UNESP, Botucatu, Sao Paulo. Brazil Date of submission 2 3 May 1991 Accepted for publication 19 August 1 9 91
Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells. Keywords: kidney, interstitial foam cells, macrophages
Address for correspondence: Dr M.Franco. Department of Pathology, School of Medicine, IJNESP, Botucatu. CEP 18610. ,580 Paulo, Brazil.
Introduction Interstitial foam cells may be found in cases of glomerulonephritis, particularly with a nephrotic syndrome'. Based on morphological studies, they seem to be derived from the endothelium of lymphatic capillaries, from degenerative and defunct tubular epithelial cells, from macrophages and from fibroblast^^.^. To our knowledge there is only one previous study using immunohistochemica1 techniques to characterize the nature of those cells, and which concluded that they belong to the monocyte-macrophage lineage4. However, Pirani, in a text-book on renal pathology, recently stated that the
Brief reports
References 1. Weeks DA. Beckwith JB, Mierau GW. Luckey DW. Rhabdoid tumor
of kidney. A report of 1 1 1 cases from the National Wilms’ Tumor Study Pathology Center. Am. J. Surg. Pathol. 1989; 13: 439-458. 2. Fletcher CDM, McKee PH. Extrarenal rhabdoid tumour. In: Fletcher CDM. McKee PH, eds. Pathobiology of Soft Tissue Tumours. Edinburgh: Churchill Livingstone. 1990; 308-31 1 . 3. Tsuneyoshi M. Daimaru Y , Hashimoto H. Enjoji M. The existence of rhabdoid cells in specified soft tissue sarcomas. Histopathological.
ultrastructural and immunohistochemical evidence. Virchows Archiv. [Pathol. Anat.] 1987; 411; 509-514. 4, Tsokos M, Kouraklis G. Chandra RS, Bhagavan BS, Triche TI. Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochernical phenotype. Arch. Pathol. Lab. Med. 1989: 113; 115-120. 5. Harris M, Eyden BP. Joglekar VM. Rhabdoid tumour of the bladder: a histological, ultrastructural and irnmunohistochemical study. Histopathology 19 8 7; 1 1 ; 108 3- 1092.
Histopathology 1992, 20, 170-173
BRIEF REPORT
Intraorbital rhabdoid tumour following bilateral retinoblastoma N. W ALFORD, R. DEFERRAI* , R. M.SLATER*, J .F .M.DELEMARRE, K .P .DINGEMANS, M.A.VAN DEN BERGH WEERMAN & P.A.VOUTEJDepartment of Pathological Anatomy, *Institute of Human Genetics and tDepartment of Paediatric Oncology, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands Date of submission 22 February 199 1 Accepted for publication 1 7 July 1991
Keywords: rhabdoid tumour, retinoblastoma, nephroblastoma
Introduction Since their first description in the kidney, primary rhabdoid tumours have been described arising in the brain, thymus, bladder, liver, heart, soft tissues, paravertebral region and the prostate region, as well as a single intraorbital case’. We report a second case of intraorbital rhabdoid tumour, of particular interest as arising in the right orbit of a 3-year-old child previously treated for bilateral retinoblastoma.
Case report The patient, a boy, first presented at the age of 2 months with bilateral retinoblastoma, treated by left-sided enucleation and right-sided radiotherapy (lateral field 4 5 Gy), with apparent cure. Histologically, the tumour was a well-differentiated retinoblastoma with well-formed Flexner rosettes. Address for correspondence: Dr J.F.M.Delemarre. Department of Pathological Anatomy, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
Twenty-seven months after first presentation the patient was seen again with a slowfy progressive exophthalmos on the right side. Investigation showed a retrobulbar mass eroding through the sphenoid bone into the middle cranial fossa. Ophthalmoscopy showed no evidence of recurrence of retinoblastoma, and the optic nerve appeared on CT-scan to be normal. Investigation at this time showed no evidence of tumour elsewhere in the body, and in particular no ultrasonographic or roentgenographic evidence of a primary kidney tumour. The patient was treated with chemotherapy and radiotherapy but failed to respond. He died at home as a result of intracranial tumour progression and autopsy was not performed. PATHOLOGICAL FINDINGS
Biopsy material from the right orbit showed a tumour composed of sheets of non-cohesive cells having abundant eosinophilic cytoplasm and large, often eccentric, nuclei with vesicular, clumped chromatin and single central nucleoli (Figure 1a). Rounded hyaline eosinophilic bodies were frequently seen in the cytoplasm. Immunocytochemical staining demonstrated a population of cells strongly positive for cytokeratin (Figure l c )
Brief reports
171
Figure 1 . Tumour section: a typical rhabdoid features with prominent central nucleoli and occasional intracytoplasmic cytoplasmic hyaline bodies (arrow) positive for b vimentin and c cytokeratin. a H & E. x 3SO. b Vimentin. x 230. c Cytokeratin. x 230.
and a population positive for vimentin (Figure lb). The presence of some weaker, more diffuse staining for neuron-specific enolase and for S-100 protein was also noted. Chromogranin, synaptophysin, glial fibrillary acidic protein and desmin immunostaining was negative. By electronmicroscopy the cells showed abundant intracytoplasmic organelles, specifically mitochondria and smooth and rough endoplasmic reticulum, the latter often dilated, and some lysosomes. Three sorts of intracytoplasmic filaments were seen: in some cells intermediate filaments were arranged in whorls which often incorporated other intracellular organelles and which sometimes occupied the bulk of the extranuclear space; more frequently filaments of similar size were arranged in irregular bundles, often around the nucleus: and there were also structures with the morphological features of tonofibrils. Occasional small neurosecretorytype granules were present. Cell surfaces sometimes showed microvillus-like protrusions and some small intercellular junctions were present. A monolayer culture of the tumour was established and cytogenetic analysis carried out. The tumour was hypotetraploid with a range of between 76 and 95 chromosomes per cell and a mode at 8 7. There were only two normal copies of chromosomes 4 , 1 5 and 18 in each metaphase, and in addition the Y chromosome was missing. The majority of cells also had only two copies of chromosome 1 3 , but two metaphases were found with
Table 1 . Clonal structural variations detected in tumour culture ( 1 2 metaphases)*
der(2)t(2;?)(q11;?) de1(5)(q13) der(5)t(1:5)(q21;q31) der(7)t(5;7)(qlI ;q3 1) de1(9)(q2lq32) der(1 l)t(ll:?)(p13:?) der(1 l)t(5;1l)(q22:q23) der(l2)t(12:?)(q22:?)
1 COPY 1 COPY 1 COPY 2 copies 2 copies 2 copies 2 copies 1 COPY
* excluding chromosome 1.
three copies. No structural changes, however, were found in chromosome 13. Clonal structural variation involved chromosomes 1, 2 , 5 . 9, 11 and 12, some variants being present as two copies, indicating that the tumour had undergone polyploidization during its progression. There were up to seven structurally abnormal copies of chromosome 1 in each metaphase involving breakpoints in regions lp36, l p 3 2 , l q 2 1 and lq23. Other clonal changes are listed in Table 1. Electronmicroscopy was carried out on the cells of the monolayer culture. This showed preservation of the characteristic intracytoplasmic filamentous whorls seen in the original tumour (Figure 2 ) .
172
Brief reports
Figure 2. Electronmicrograph of cell from monolayer culture
showing characteristic intracytoplasmic filamentous whorl. x 10000.
Discussion This tumour meets the morphological, immunocytochemica1 and electronmicroscopic criteria for diagnosis of rhabdoid tumours’. It has recently been suggested2 that many of the reported cases of extrarenal rhabdoid tumours are of diverse origins and would better be designated as ‘pseudo-rhabdoid’; it is not apparent, however, on what criteria the distinction of true and pseudo-rhabdoid tumours can be made. The presence of isolated rhabdoid-like cells has been described in a variety of tumours, usually in adults, and with no apparent worsening of prognosis3. Extrarenal rhabdoid tumours, on the other hand, tend to arise, like the renal variety, in infants or children and pursue the same aggressive clinical course with poor response to therapy4.
A number of possible explanations are entertained for the association of rhabdoid tumour and retinoblastoma in this patient: 1 Since the patient has a genetic predisposition to retinoblastoma it is possible that this tumour is a retinoblastoma which has undergone regressive or metaplastic change to show rhabdoid-like features, conceivably in response to radiation. We consider this unlikely on account of the lack of clinically demonstrable retinal involvement as well as the absence of characteristic changes in chromosome 13. 2 Retinoblastoma is known to be associated with a particularly high incidence of second malignant tumour development, both in the field of radiation and elsewhere5.The second tumour is most commonly an
Brief reports
osteosarcoma, but associations appear to exist also with melanoma, other skin cancers and rhabdomyosarcoma5. Interestingly, the latter association was documented prior to the delineation of rhabdoid tumour as an entity distinct from rhabdomyosarcoma in 198 1.The time gap of 2 7 months in this case would be unusually short for a radiogenic tumour, but is not inconsistent with published cases5. 3 An association has been reported between malignant rhabdoid tumour of the kidney and a variety of primitive neuroepithelial malignancies in the central nervous system, the brain tumour frequently preceding clinically that in the kidneyh. This association remains unexplained. The present case represents the first report of a primary extrarenal rhabdoid tumour and primary neuroepithelial tumour in the same patient: and it is conceivable that the presence of such an association in this case represents an analogous process to that seen with the renal rhabdoid tumours.
173
References 1. Rootman J, Damji KF. Dimmick JE. Malignant rhabdoid tumour of the orbit. Ophthalmology 1989: 96; 1650-1654. 2. Mierau GW. Weeks DA, Beckwith ]B. Anaplastic Wilms' tumor and other clinically aggressive childhood renal neoplasms: ultrastructural and immunocytochemical features. Ultrastruct. Pathol. 1989: 13; 225-248. 3 . Tsuneyoshi M. Daimaru Y . Hashimoto H. Enjoji M. The existence of rhabdoid cells in specified soft tissue sarcomas: histopathological. ultrastructural and immunohistochemical evidence. Virchows Archiv. [Pathol. Anat.] 1987: 411; 509-514. 4. Sotelo-Avila C. Gonzales-Crussi F. Demello D et al. Renal and extrarenal rhabdoid tumors in children: a clinicopathological study of 1 4 patients. Semin. Diag. Pathol. 1986: 3: 151-163. 5. Meadows AT, D'Angio GJ. Mike V et al. Patterns of second malignant neoplasms in children. Cancer 1977; 40: 1903-1 91 I . 6 . Bonnin JM, Rubinstein LJ. Palmer NF, Beckwith JB. The association of embryonal tumors originating in the kidney and in the brain. A report of seven cases. Cancer 1984: 54; 2137-2146.
Acknowledgements The work of Ms Deferrai was funded in part by an EEC grant.
Histopathology 1992, 20, 173-1 76
BRIEF REPORT
Renal interstitial foam cells are macrophages M.FRANC0, F-SCHMITT, W.A.REJAIL1, R.M.VIER0 & C.E.BACCHI Department of Pathology, School of Medicine, UNESP, Botucatu, Sao Paulo. Brazil Date of submission 2 3 May 1991 Accepted for publication 19 August 1 9 91
Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells. Keywords: kidney, interstitial foam cells, macrophages
Address for correspondence: Dr M.Franco. Department of Pathology, School of Medicine, IJNESP, Botucatu. CEP 18610. ,580 Paulo, Brazil.
Introduction Interstitial foam cells may be found in cases of glomerulonephritis, particularly with a nephrotic syndrome'. Based on morphological studies, they seem to be derived from the endothelium of lymphatic capillaries, from degenerative and defunct tubular epithelial cells, from macrophages and from fibroblast^^.^. To our knowledge there is only one previous study using immunohistochemica1 techniques to characterize the nature of those cells, and which concluded that they belong to the monocyte-macrophage lineage4. However, Pirani, in a text-book on renal pathology, recently stated that the
