[Gastrointestinal stromal tumor and renal transplant]. / Tumor del estroma gastrointestinal y trasplante renal.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Kikuchi-Fujimoto disease and systemic lupus erythematosus.

Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is an infrequent idiopathic disorder. It has been associated with autoimmune disorders, of which systemic lupus erythematosus is the most outstanding. The basis of its diagnosis relies on the histological examination of lymph nodes, which typically reveals necrosis surrounded by histiocytes with crescentic nucleus, immunoblasts and plasma cells, and absence of neutrophils. We report the case of a 27-year-old Argentinian female patient without any relevant past medical history to demonstrate the correlation between Kikuchi-Fujimoto disease and systemic lupus erythematosus.

Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation.

We evaluated whether the lack of TNF-α signaling increases mucosal levels of annexin A1 (AnxA1); the hypothesis stems from previous findings showing that TNF-α neutralization in Crohn's disease patients up-regulates systemic AnxA1 expression. Biopsies from healthy volunteers and patients under anti-TNF-α therapy with remittent ulcerative colitis (UC) showed higher AnxA1 expression than those with active disease. We also evaluated dextran sulfate sodium (DSS)-acute colitis in TNF-α receptor 1 KO (TNFR1-/-) strain with impaired TNF-α signaling and C57BL/6 (WT) mice. Although both strains developed colitis, TNFR1-/- mice showed early clinical recovery, lower myeloperoxidase (MPO) activity and milder histopathological alterations. Colonic epithelium from control and DSS-treated TNFR1-/- mice showed intense AnxA1 expression and AnxA1+ CD4+ and CD8+ T cells were more frequent in TNFR1-/- animals, suggesting an extra supply of AnxA1. The pan antagonist of AnxA1 receptors exacerbated the colitis outcome in TNFR1-/- mice, supporting the pivotal role of AnxA1 in the early recovery. Our findings demonstrate that the TNF-α signaling reduction favors the expression and biological activity of AnxA1 in inflamed intestinal mucosa.

Evolución inusual de un carcinoma urotelial variante plasmocitoide / Unusual evolution of a plasmacytoid urothelial carcinoma of the bladder

Se comunica el caso de un hombre de 63 años que acudió a la consulta debido a un episodio de hematuria, por lo que se realizó una resección vesical transuretral, con diagnóstico de carcinoma infiltrante. Se llevó a cabo una cistectomía radical. En la pieza se identificó un tumor ulcerovegetante en la base de la vejiga. La microscopia mostró una infiltración de células malignas de aspecto plasmocitoide, positivas para CK7 y negativas para CK20 y CD138. El diagnóstico fue de carcinoma urotelial plasmocitoide. Tres meses después el paciente reingresó por taponamiento cardíaco. El examen citológico del líquido pericárdico demostró células similares a las de su carcinoma primario. El paciente murió 6 meses después del diagnóstico. El carcinoma urotelial representa el 90% de los carcinomas vesicales. Teniendo en cuenta sus variantes histopatológicas la forma plasmocitoide es inusual. Sus signos y síntomas no se presentan hasta que la enfermedad ha progresado a una etapa avanzada, lo que conlleva un mal pronóstico y curso agresivo. La histología es característica: las células presentan aspecto plasmocitoide y son por lo general CK7 y CK20 positivas. Hasta un 94% pueden ser positivas para CD138. Los principales diagnósticos diferenciales son plasmocitoma y linfoma con diferenciación plasmocitoide. La afectación cardiovascular es infrecuente. El carcinoma urotelial plasmocitoide es una entidad histopatológica que es difícil de diagnosticar debido su baja frecuencia, requiere el diagnóstico diferencial con otras enfermedades y su comportamiento es agresivo y atípico (AU)

A 63 year old man presented with hematuria and underwent a transurethral resection of the bladder. A diagnosis of muscle invasive carcinoma was made and a radical cystectomy was performed. An ulcerating vegetative tumour was present in the base of the bladder. Microscopy revealed infiltration by atypical cells with plasmacytoid appearance and which were positive for CK7 and negative for CK20 and CD138. The final diagnosis was plasmacytoid urothelial carcinoma. Three months later the patient was readmitted with a cardiac tamponade. Cytology of the pericardial fluid revealed cells similar to those of the primary carcinoma. He died six months after initial diagnosis. Urothelial carcinoma represents 90% of all bladder carcinomas and the plasmacytoid form is an unusual variant which only becomes clinically manifest when it reaches an advanced stage and behaves aggressively with a poor prognosis. It has a characteristic histology with cells with plasmacytoid appearance which are usually positive for CK7 and CK20. Up to 94% can be positive for CD138. The main differential diagnoses are plasmacytoma and plasmacytoid lymphoma. Cardiovascular involvement is unusual. Plasmacytoid urothelial carcinoma poses diagnostic problems due to its rarity. Careful differential diagnosis should be made. Its behavior is aggressive and atypical (AU)

Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers.

Clear cell renal carcinoma is the most frequent type of renal carcinoma. Recently, attention has been focused in the expression of angiogenic factors by these tumors, which would justify in part their capacity to grow, invade and disseminate, stating a worse evolution of those patients with an unfavorable angiogenic profile. 83 samples of nephrectomy with a diagnosis of clear cell renal cell carcinoma were studied. Clinical and pathological data were collected. Tumors were studied to assess immunohistochemical expression of the following markers: VEGF-A, HIF-1α, CD34 and Ki67. Results indicated a direct linear relationship between expressions of these four markers. Besides, the expression of HIF-1α was directly related to Furhman grade, invasion of the renal vein and tumor stage. Likewise, tumor proliferation index, assessed with Ki67, was directly related to the presence of necrosis, capsular invasion and advanced tumor stage. Regarding the expression of CD34, vascular density was inversely related to tumor necrosis and overall survival. These findings are controversial compared with the available literature. Then, a research scenery would be open, where the importance of generating prospective and more standardized studies are highlighted to determine the role of these angiogenic factors in tumor evolution and prognostic evaluation of these tumors.

El carcinoma renal de células claras es la variante más frecuente de carcinoma renal. En los últimos años, la atención se ha enfocado en la expresión de factores angiogénicos por estos tumores, lo que justificaría en parte su capacidad de crecer, invadir y diseminarse, determinando una peor evolución de aquellos pacientes con un perfil angiogénico desfavorable. Se estudiaron 83 piezas de nefrectomía con diagnóstico de carcinoma renal de células claras. Se recolectaron datos clínicos y patológicos. Los tumores fueron estudiados para evaluar la expresión inmunohistoquímica de los siguientes marcadores: VEGF-A, HIF-1α, CD34 y Ki67. Los resultados indicaron una relación lineal directa entre la expresión de estos cuatro marcadores. Además, la expresión de HIF-1α se encontraba directamente relacionada con el grado de Furhman, la invasión de la vena renal y el estadio tumoral. Asimismo, el índice de proliferación tumoral, evaluado con Ki67, se hallaba directamente relacionado con la presencia de necrosis, la invasión capsular y el estadio tumoral avanzado. Con respecto a la expresión de CD34, mientras mayor es la densidad vascular, menor es la necrosis tumoral y menor la sobrevida global. Los hallazgos resultan controvertidos en comparación con la literatura disponible. Se abriría, entonces, un escenario de investigación donde se destaca la importancia de generar estudios prospectivos y más estandarizados para determinar el rol que cumplen estos factores angiogénicos en la evolución tumoral y la posibilidad de estandarizar resultados que permitan un mejor estudio diagnóstico y pronóstico de estos tumores.

Pancreatic plasmacytoma with biliary obstruction as a manifestation of multiple myeloma relapse

No disponible

Timoma esclerosante (antiguo): Un tumor poco frecuente de mediastino anterior. Presentación de un caso / Sclerosing thymoma: A rare anterior mediastinal tumour. A case report

El timoma esclerosante es un tumor muy poco frecuente de mediastino anterior que representa menos del 1% de los timomas. Se presenta el caso de un hombre de 46 años, asintomático, al cual se le diagnosticó un tumor mediastínico en una radiografía torácica de control. Se realizó una biopsia transtorácica que no fue concluyente. En la cirugía se observó un tumor sólido adherido a la pared anterior del tórax, pleura y pericardio. Microscópicamente la neoplasia presentaba un 90% de estroma fibrocolagenoso con aisladas células epiteliales sin atipia y abundantes linfocitos, diagnosticándose un timoma esclerosante. El paciente evolucionó favorablemente. Existen importantes diagnósticos diferenciales a considerar en lesiones mediastínicas esclerosantes, como una mediastinitis esclerosante, un tumor fibroso solitario yalgunos linfomas. Para un correcto diagnóstico histopatológico es necesario un amplio muestreo del tumor y realizar estudios de inmunohistoquímica (AU)

Sclerosing thymoma is a very rare anterior mediastinal tumour accounting for less than 1% of all thymomas. We report a case of an asymptomatic 46 year-old man with a mediastinal tumour discovered on a routine chest x-ray. A transthoracic tumour biopsy was inconclusive. Surgery revealed a tumour attached to the anterior thoracic wall, pleura and pericardium. Histologically, 90% of the neoplasm consisted of a fibrocollagen stroma with isolated epithelial cells which showed no atypia; lymphoid cells were not abundant. A diagnosis of sclerosing thymoma was made and the patient recovered well. The most important differential diagnoses to be considered in sclerosing lesions of the anterior mediastinum are sclerosing mediastinitis, solitary fibrous tumour and lymphomas. For a correct histopathological diagnosis, extensive tumour sampling is necessary and the immunohistochemistry must be studied (AU)

Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers. / Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers.

Clear cell renal carcinoma is the most frequent type of renal carcinoma. Recently, attention has been focused in the expression of angiogenic factors by these tumors, which would justify in part their capacity to grow, invade and disseminate, stating a worse evolution of those patients with an unfavorable angiogenic profile. 83 samples of nephrectomy with a diagnosis of clear cell renal cell carcinoma were studied. Clinical and pathological data were collected. Tumors were studied to assess immunohistochemical expression of the following markers: VEGF-A, HIF-1α, CD34 and Ki67. Results indicated a direct linear relationship between expressions of these four markers. Besides, the expression of HIF-1α was directly related to Furhman grade, invasion of the renal vein and tumor stage. Likewise, tumor proliferation index, assessed with Ki67, was directly related to the presence of necrosis, capsular invasion and advanced tumor stage. Regarding the expression of CD34, vascular density was inversely related to tumor necrosis and overall survival. These findings are controversial compared with the available literature. Then, a research scenery would be open, where the importance of generating prospective and more standardized studies are highlighted to determine the role of these angiogenic factors in tumor evolution and prognostic evaluation of these tumors.

Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers / Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers.

Clear cell renal carcinoma is the most frequent type of renal carcinoma. Recently, attention has been focused in the expression of angiogenic factors by these tumors, which would justify in part their capacity to grow, invade and disseminate, stating a worse evolution of those patients with an unfavorable angiogenic profile. 83 samples of nephrectomy with a diagnosis of clear cell renal cell carcinoma were studied. Clinical and pathological data were collected. Tumors were studied to assess immunohistochemical expression of the following markers: VEGF-A, HIF-1α, CD34 and Ki67. Results indicated a direct linear relationship between expressions of these four markers. Besides, the expression of HIF-1α was directly related to Furhman grade, invasion of the renal vein and tumor stage. Likewise, tumor proliferation index, assessed with Ki67, was directly related to the presence of necrosis, capsular invasion and advanced tumor stage. Regarding the expression of CD34, vascular density was inversely related to tumor necrosis and overall survival. These findings are controversial compared with the available literature. Then, a research scenery would be open, where the importance of generating prospective and more standardized studies are highlighted to determine the role of these angiogenic factors in tumor evolution and prognostic evaluation of these tumors.

Clinicopathological features of aggressive B-cell lymphomas including B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell and Burkitt lymphomas: a study of 44 patients from Argentina.

Aggressive B-cell lymphomas incorporate a wide spectrum of lymphomas that pose challenges in diagnosis as well as treatment. We evaluated the clinicopathological features of 44 patients with aggressive B-cell lymphomas which were classified into 3 groups based on the World Health Organization 2008 classification as follows: including 30 cases of diffuse large B-cell lymphoma (DLBCL), 8 cases of Burkitt lymphoma (BL) and 6 cases of B-cell lymphoma, unclassifiable, with features intermediate between Burkitt lymphoma and diffuse large B-cell lymphoma (BCLU). Male predominance was observed in BL and BCLU groups and the mean age varied from 29 years in BL, 61 years in DLBCL and 70 years in BCLU. Patients with BCLU presented at more advanced stages and had a higher international prognostic index. By immunohistochemistry, they shared characteristics of both BL (including more frequent expression of SOX11) and DLBCL. FISH analyses showed three cases with more than one rearrangement: one MYC/BCL2 and two BCL2/BCL6, in addition to which one case with BCL2/IGH translocation and another with MYC rearrangement were also detected. The mean follow-up survival time of BCLU was 6.6 months, which was significantly shorter in comparison to DLBCL (31 months) and BL (30 months), respectively. The importance of recognizing this BCLU group relies on its different clinical course, poor prognosis and shorter survival than DLBCL and BL. An accurate diagnosis is critical for risk stratification and to improve therapeutic approaches and outcomes.

[Primary hydatid disease of the tibia. case report]. / Hidiatidosis osea primaria de tibia: presentación de un caso.

Hydatidosis is an endemic disease in different parts of the world. Its causal agent is the cestode from the genus Echinococcus. The most commonly affected organs in humans are liver and lung. Bone hydatid disease is a very rare entity, accounting for 0.5 to 4% of total cases. We report a case of a 58 year-old woman from La Rioja, Argentina, who consulted for left infapatellar pain and walking disability of eight months duration. Imaging studies showed a cystic lesion which involved metaphysis and diaphysis of left proximal tibia. Surgical resection was performed and histopathological study confirmed that it was a hydatid cyst. The patient did well and completed three cycles of treatment with albendazole. Currently, she has no evidence of disease and she recovered motility of her left leg. Primary hydatid bone disease, where there is no evidence of systemic disease, is even more unusual. Tibia involvement occurs in up to 15% of the cases. These lesions clinically manifest when they suffer any type of complications. Preoperative diagnosis is mainly made by imaging studies. Lesions are usually osteolytic and can involve cortical bone and extend to soft tissues. Differential diagnosis with inflammatory processes and bone tumors should is mandatory. Treatment is surgical and prognosis is poor due to its high morbi-mortality rate and recurrence risk from 70 to 80%.

[Unusual presentation of plasma cell myeloma]. / Morfología dual de células de mieloma: inusual presentación de un caso.

A 41 year-old woman consulted because of facial pain. A magnetic resonance imaging showed a mass in the right petrous apex. A biopsy revealed a diffuse proliferation of large atypical cells with plasmablastic appearance, positive for CD138, BCL6, CD56 and p53. The proliferation factor was 80%. Monoclonal kappa light chain expression was observed. Because the unusual clinicopathological features the patient was studied to rule out systemic plasma cell myeloma. Bone scan disclosed multiple cranium osteolytic lesions; proteinogram showed hypogammaglobulinemia and immunofixation in serum and urine were negative. Afterwards, bone marrow biopsy was performed and it presented a 30% infiltration of the bone cylinder by mature plasma cells. These were monoclonal for kappa light chain with focal expression of p53 and without expression of CD56. These findings suggested the diagnosis of multiple myeloma. This case proposes a morphological spectrum of plasma cell neoplasms, showing a continuous clonal evolution of tumor cells, with an acquired plasticity of dedifferentiate, become immature and infiltrate extramedullary tissues, a fact possibly determined by accumulation of multiple genetic alterations. These findings confirm the difficulty of the differential diagnosis from histopathology study between plasmablastic lymphoma and plasmablastic transformation of plasma cell myeloma because of the nearly identical immunohistochemical profiles.

Morfología dual de células de mieloma: inusual presentación de un caso / Unusual presentation of plasma cell myeloma

Una mujer de 41 años consultó por dolor facial. En una resonancia magnética nuclear se observó una masa en el ápex del peñasco derecho. La biopsia mostró una infiltración difusa por células grandes atípicas con morfología plasmablástica, positivas para CD138, BCL6, CD56 y p53, con expresión monoclonal de cadena liviana kappa y factor de proliferación del 80%, planteando el diagnóstico diferencial entre linfoma plasmablástico versus plasmocitoma plasmablástico. Un mapeo óseo evidenció múltiples lesiones osteolíticas en cráneo; el proteinograma reveló hipogamaglobulinemia y la inmunofijación en suero y orina fueron negativas. Se realizó biopsia de médula ósea donde se observó infiltración en un 30% del cilindro óseo por células plasmáticas maduras monoclonales para kappa, con expresión focal de p53 y negativas para CD56. Estos hallazgos confirmaron el diagnóstico de mieloma múltiple. Este caso pone de manifiesto la existencia de un espectro morfológico de las neoplasias de células plasmáticas, mostrando una evolución clonal continua con una plasticidad adquirida para desdiferenciarse, volverse inmaduras e infiltrar tejidos extramedulares, posiblemente debido a acumulación de alteraciones moleculares. Por lo tanto, se evidencia la dificultad del diagnóstico diferencial histopatológico entre linfoma plasmablástico y transformación plasmablástica de mieloma múltiple, debido a sus perfiles inmunohistoquímicos casi idénticos.(AU)

A 41 year-old woman consulted because of facial pain. A magnetic resonance imaging showed a mass in the right petrous apex. A biopsy revealed a diffuse proliferation of large atypical cells with plasmablastic appearance, positive for CD138, BCL6, CD56 and p53. The proliferation factor was 80%. Monoclonal kappa light chain expression was observed. Because the unusual clinicopathological features the patient was studied to rule out systemic plasma cell myeloma. Bone scan disclosed multiple cranium osteolytic lesions; proteinogram showed hypogammaglobulinemia and immunofixation in serum and urine were negative. Afterwards, bone marrow biopsy was performed and it presented a 30% infiltration of the bone cylinder by mature plasma cells. These were monoclonal for kappa light chain with focal expression of p53 and without expression of CD56. These findings suggested the diagnosis of multiple myeloma. This case proposes a morphological spectrum of plasma cell neoplasms, showing a continuous clonal evolution of tumor cells, with an acquired plasticity of dedifferentiate, become immature and infiltrate extramedullary tissues, a fact possibly determined by accumulation of multiple genetic alterations. These findings confirm the difficulty of the differential diagnosis from histopathology study between plasmablastic lymphoma and plasmablastic transformation of plasma cell myeloma because of the nearly identical immunohistochemical profiles.(AU)

Morfología dual de células de mieloma: inusual presentación de un caso / Unusual presentation of plasma cell myeloma

Una mujer de 41 años consultó por dolor facial. En una resonancia magnética nuclear se observó una masa en el ápex del peñasco derecho. La biopsia mostró una infiltración difusa por células grandes atípicas con morfología plasmablástica, positivas para CD138, BCL6, CD56 y p53, con expresión monoclonal de cadena liviana kappa y factor de proliferación del 80%, planteando el diagnóstico diferencial entre linfoma plasmablástico versus plasmocitoma plasmablástico. Un mapeo óseo evidenció múltiples lesiones osteolíticas en cráneo; el proteinograma reveló hipogamaglobulinemia y la inmunofijación en suero y orina fueron negativas. Se realizó biopsia de médula ósea donde se observó infiltración en un 30% del cilindro óseo por células plasmáticas maduras monoclonales para kappa, con expresión focal de p53 y negativas para CD56. Estos hallazgos confirmaron el diagnóstico de mieloma múltiple. Este caso pone de manifiesto la existencia de un espectro morfológico de las neoplasias de células plasmáticas, mostrando una evolución clonal continua con una plasticidad adquirida para desdiferenciarse, volverse inmaduras e infiltrar tejidos extramedulares, posiblemente debido a acumulación de alteraciones moleculares. Por lo tanto, se evidencia la dificultad del diagnóstico diferencial histopatológico entre linfoma plasmablástico y transformación plasmablástica de mieloma múltiple, debido a sus perfiles inmunohistoquímicos casi idénticos.

A 41 year-old woman consulted because of facial pain. A magnetic resonance imaging showed a mass in the right petrous apex. A biopsy revealed a diffuse proliferation of large atypical cells with plasmablastic appearance, positive for CD138, BCL6, CD56 and p53. The proliferation factor was 80%. Monoclonal kappa light chain expression was observed. Because the unusual clinicopathological features the patient was studied to rule out systemic plasma cell myeloma. Bone scan disclosed multiple cranium osteolytic lesions; proteinogram showed hypogammaglobulinemia and immunofixation in serum and urine were negative. Afterwards, bone marrow biopsy was performed and it presented a 30% infiltration of the bone cylinder by mature plasma cells. These were monoclonal for kappa light chain with focal expression of p53 and without expression of CD56. These findings suggested the diagnosis of multiple myeloma. This case proposes a morphological spectrum of plasma cell neoplasms, showing a continuous clonal evolution of tumor cells, with an acquired plasticity of dedifferentiate, become immature and infiltrate extramedullary tissues, a fact possibly determined by accumulation of multiple genetic alterations. These findings confirm the difficulty of the differential diagnosis from histopathology study between plasmablastic lymphoma and plasmablastic transformation of plasma cell myeloma because of the nearly identical immunohistochemical profiles.

A renal variant of Fabry disease: A case with a novel Gal A hemizygote mutation.

BACKGROUND: Fabry disease is caused by an X-linked recessive inborn error of glycosphingolipid metabolism with deficient activity of a lysosomal enzyme, alpha-galactosidase A (α-GalA). CASE PRESENTATION: A 46 year-old man with progressive kidney disease showed on kidney biopsy electron microscopic evidence of Fabry disease. The patient had no systemic manifestations of Fabry disease, despite residual α-GalA activity, therefore genetic testing was done by direct DNA sequencing, demonstrating a new GAL A gene mutation (C174G-exon 3). After three years of enzyme replacement therapy (agalsidase beta) treatment, a second biopsy was done. Although there was demonstrable clearance of intracellular inclusions, remarkable podocyte activation was evident. CONCLUSIONS: This report represents an unusual renal variant of Fabry disease and provides histologic data on long-term follow up after enzyme replacement therapy.