Mayo Graduate School Of Medicine

A48-year-old female was admitted to the hospital with atrial fibrillation. Her medical history was significant for systemic lupus erythematosus (SLE) diagnosed 28 years ago, with low dose prednisone treatment for the past 15 years.

In the past year, the patient had experienced progressive difficulty swallowing and often choked on her food, resulting in a 35-pound weight loss. She also mentioned that she had been bruising easily.

On examination, the patient had bruising around her eyes and a thick, enlarged tongue with clear marks of her teeth visible on the surface.

Which test will most likely lead to a diagnosis?

1. Magnetic resonance imaging (MRI) of pituitary gland;
2. Abdominal fat pad biopsy;
3. Thyroid stimulating hormone (TSH) level;
4. Serum Angiotensin converting enzyme (ACE) levels
5. Tongue biopsy

Discussion

The answer is B: abdominal fat pad biopsy. Macroglossia, especially in adults, is a rare clinical finding and is most often associated with amyloidosis.1 It has also been rarely described in association with acromegaly, hypothyroidism, and sarcoidosis. In children, macroglossia may be seen in a variety of conditions including cretinism, Down syndrome, Beckwith-Wiedemann syndrome, and various storage diseases.2 Lymphangioma of the tongue may also present with macroglossia.3

Another finding classically seen in amyloidosis is palpebral purpura.4 The occurrence of these two physical findings together in this patient strongly suggests the diagnosis of amyloidosis. The amyloidoses are now considered a group of diseases characterized by extracellular deposition of insoluble fibrillar proteins in various organs secondary to misfolding of proteins.

They include not only primary and secondary amyloidosis but also Alzheimer’s, prion diseases, many other neurodegenerative disorders, and some types of cystic fibroses.5

Traditionally, amyloidosis was described as one of three types: primary, secondary, and heritable. Primary amyloidosis is the most common type and results from deposition of fragments of light chain immunoglobulin deposits. It is most frequently associated with plasma cell dyscrasias. Secondary, or AA, amyloidosis occurs in association with inflammatory conditions and results from deposition of fragments of the acute phase reactant serum amyloid A. Familial amyloidoses or the ATTR amyloidoses are a fairly heterogeneous group with different proteins associated with different disorders.5

The typical findings seen in this case are associated with primary amyloidosis.4 The presence of primary amyloidosis was confirmed in this case by a bone marrow biopsy. This patient had SLE, but SLE is usually not complicated by the development of amyloidosis, although rare cases in literature have been described.6 Also, as mentioned above, secondary amyloidosis is usually characterized by AA rather than AL amyloidosis.

The diagnosis of amyloidosis is made pathologically when an involved organ is biopsied. When clinical suspicion is high and no organ has been biopsied, the simplest procedure is to obtain an abdominal fat pad biopsy and stain it with Congo red. This test is 85% sensitive in patients with primary amyloidosis.4 TH

References

1. Xavier SD, Bussoloti IF, Muller H. Macroglossia secondary to systemic amyloidosis: case report and literature review. Ear Nose Throat J. 2005 Jun;84(6):358-361.
2. Wolford LM, Cottrell DA. Diagnosis of macroglossia and indications for reduction glossectomy. Am J Orthod Dentofacial Orthop. 1996 Aug;110:170-177.
3. Gulemann M, Katz J. Macroglossia combined with lymphangioma: a case report. J Clin Pediatr Dent. 2003 Winter;27(2):167-169.
4. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997; 337: 898-909.
5. Merlini G, Bellotti V. Mechanisms of disease: molecular mechanisms of amyloidosis. N Engl J Med. 2003; 349:583-596.
6. Al-Hoqail I, Naddaf H, Al-Rikabi A, et al. Systemic lupus erythematosus and amyloidosis. Clin Rheumatol. 1997 Jun;16(4):422-424.on.

A48-year-old female was admitted to the hospital with atrial fibrillation. Her medical history was significant for systemic lupus erythematosus (SLE) diagnosed 28 years ago, with low dose prednisone treatment for the past 15 years.

In the past year, the patient had experienced progressive difficulty swallowing and often choked on her food, resulting in a 35-pound weight loss. She also mentioned that she had been bruising easily.

On examination, the patient had bruising around her eyes and a thick, enlarged tongue with clear marks of her teeth visible on the surface.

Which test will most likely lead to a diagnosis?

1. Magnetic resonance imaging (MRI) of pituitary gland;
2. Abdominal fat pad biopsy;
3. Thyroid stimulating hormone (TSH) level;
4. Serum Angiotensin converting enzyme (ACE) levels
5. Tongue biopsy

Discussion

The answer is B: abdominal fat pad biopsy. Macroglossia, especially in adults, is a rare clinical finding and is most often associated with amyloidosis.1 It has also been rarely described in association with acromegaly, hypothyroidism, and sarcoidosis. In children, macroglossia may be seen in a variety of conditions including cretinism, Down syndrome, Beckwith-Wiedemann syndrome, and various storage diseases.2 Lymphangioma of the tongue may also present with macroglossia.3

Another finding classically seen in amyloidosis is palpebral purpura.4 The occurrence of these two physical findings together in this patient strongly suggests the diagnosis of amyloidosis. The amyloidoses are now considered a group of diseases characterized by extracellular deposition of insoluble fibrillar proteins in various organs secondary to misfolding of proteins.

They include not only primary and secondary amyloidosis but also Alzheimer’s, prion diseases, many other neurodegenerative disorders, and some types of cystic fibroses.5

Traditionally, amyloidosis was described as one of three types: primary, secondary, and heritable. Primary amyloidosis is the most common type and results from deposition of fragments of light chain immunoglobulin deposits. It is most frequently associated with plasma cell dyscrasias. Secondary, or AA, amyloidosis occurs in association with inflammatory conditions and results from deposition of fragments of the acute phase reactant serum amyloid A. Familial amyloidoses or the ATTR amyloidoses are a fairly heterogeneous group with different proteins associated with different disorders.5

The typical findings seen in this case are associated with primary amyloidosis.4 The presence of primary amyloidosis was confirmed in this case by a bone marrow biopsy. This patient had SLE, but SLE is usually not complicated by the development of amyloidosis, although rare cases in literature have been described.6 Also, as mentioned above, secondary amyloidosis is usually characterized by AA rather than AL amyloidosis.

The diagnosis of amyloidosis is made pathologically when an involved organ is biopsied. When clinical suspicion is high and no organ has been biopsied, the simplest procedure is to obtain an abdominal fat pad biopsy and stain it with Congo red. This test is 85% sensitive in patients with primary amyloidosis.4 TH

References

1. Xavier SD, Bussoloti IF, Muller H. Macroglossia secondary to systemic amyloidosis: case report and literature review. Ear Nose Throat J. 2005 Jun;84(6):358-361.
2. Wolford LM, Cottrell DA. Diagnosis of macroglossia and indications for reduction glossectomy. Am J Orthod Dentofacial Orthop. 1996 Aug;110:170-177.
3. Gulemann M, Katz J. Macroglossia combined with lymphangioma: a case report. J Clin Pediatr Dent. 2003 Winter;27(2):167-169.
4. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997; 337: 898-909.
5. Merlini G, Bellotti V. Mechanisms of disease: molecular mechanisms of amyloidosis. N Engl J Med. 2003; 349:583-596.
6. Al-Hoqail I, Naddaf H, Al-Rikabi A, et al. Systemic lupus erythematosus and amyloidosis. Clin Rheumatol. 1997 Jun;16(4):422-424.on.

A48-year-old female was admitted to the hospital with atrial fibrillation. Her medical history was significant for systemic lupus erythematosus (SLE) diagnosed 28 years ago, with low dose prednisone treatment for the past 15 years.

In the past year, the patient had experienced progressive difficulty swallowing and often choked on her food, resulting in a 35-pound weight loss. She also mentioned that she had been bruising easily.

On examination, the patient had bruising around her eyes and a thick, enlarged tongue with clear marks of her teeth visible on the surface.

Which test will most likely lead to a diagnosis?

1. Magnetic resonance imaging (MRI) of pituitary gland;
2. Abdominal fat pad biopsy;
3. Thyroid stimulating hormone (TSH) level;
4. Serum Angiotensin converting enzyme (ACE) levels
5. Tongue biopsy

Discussion

The answer is B: abdominal fat pad biopsy. Macroglossia, especially in adults, is a rare clinical finding and is most often associated with amyloidosis.1 It has also been rarely described in association with acromegaly, hypothyroidism, and sarcoidosis. In children, macroglossia may be seen in a variety of conditions including cretinism, Down syndrome, Beckwith-Wiedemann syndrome, and various storage diseases.2 Lymphangioma of the tongue may also present with macroglossia.3

Another finding classically seen in amyloidosis is palpebral purpura.4 The occurrence of these two physical findings together in this patient strongly suggests the diagnosis of amyloidosis. The amyloidoses are now considered a group of diseases characterized by extracellular deposition of insoluble fibrillar proteins in various organs secondary to misfolding of proteins.

They include not only primary and secondary amyloidosis but also Alzheimer’s, prion diseases, many other neurodegenerative disorders, and some types of cystic fibroses.5

Traditionally, amyloidosis was described as one of three types: primary, secondary, and heritable. Primary amyloidosis is the most common type and results from deposition of fragments of light chain immunoglobulin deposits. It is most frequently associated with plasma cell dyscrasias. Secondary, or AA, amyloidosis occurs in association with inflammatory conditions and results from deposition of fragments of the acute phase reactant serum amyloid A. Familial amyloidoses or the ATTR amyloidoses are a fairly heterogeneous group with different proteins associated with different disorders.5

The typical findings seen in this case are associated with primary amyloidosis.4 The presence of primary amyloidosis was confirmed in this case by a bone marrow biopsy. This patient had SLE, but SLE is usually not complicated by the development of amyloidosis, although rare cases in literature have been described.6 Also, as mentioned above, secondary amyloidosis is usually characterized by AA rather than AL amyloidosis.

The diagnosis of amyloidosis is made pathologically when an involved organ is biopsied. When clinical suspicion is high and no organ has been biopsied, the simplest procedure is to obtain an abdominal fat pad biopsy and stain it with Congo red. This test is 85% sensitive in patients with primary amyloidosis.4 TH

References

1. Xavier SD, Bussoloti IF, Muller H. Macroglossia secondary to systemic amyloidosis: case report and literature review. Ear Nose Throat J. 2005 Jun;84(6):358-361.
2. Wolford LM, Cottrell DA. Diagnosis of macroglossia and indications for reduction glossectomy. Am J Orthod Dentofacial Orthop. 1996 Aug;110:170-177.
3. Gulemann M, Katz J. Macroglossia combined with lymphangioma: a case report. J Clin Pediatr Dent. 2003 Winter;27(2):167-169.
4. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med 1997; 337: 898-909.
5. Merlini G, Bellotti V. Mechanisms of disease: molecular mechanisms of amyloidosis. N Engl J Med. 2003; 349:583-596.
6. Al-Hoqail I, Naddaf H, Al-Rikabi A, et al. Systemic lupus erythematosus and amyloidosis. Clin Rheumatol. 1997 Jun;16(4):422-424.on.

A48-year-old male presents with three weeks of worsening shortness of breath and pleuritic chest discomfort. A week before the onset of these symptoms, he noticed increasing fatigue, weight loss, abdominal discomfort, and persistent hematuria He was otherwise healthy and was taking no medications.

Physical examination reveals a tachypneic yet hemodynamically stable patient, with left upper quadrant fullness. CT chest and abdomen, reveal the following (see right).

You suspect that this finding is secondary to an extrapulmonary process. What unifying diagnosis most likely accounts for these findings? What is your diagnosis?

1. Antiphospholipid syndrome
2. Antithrombin III deficiency
3. Renal cell carcinoma
4. Protein C deficiency
5. Prostate carcinoma

Discussion

The answer is C: Renal cell carcinoma (RCC) with caval extension causing PE; this suggests that the PE was due to tumor thrombus. The photo on p. 8 shows areas of increased attenuation in the prominent right and left pulmonary arteries, consistent with a saddle pulmonary embolism. An MRI of the abdomen (see photo above) reveals a large left renal mass extending to Gerota’s fascia and into the left renal vein, protruding slightly into the inferior vena cava (IVC).

The MRI demonstrates an occlusive thrombus in the left renal vein with propagation into the inferior vena cava. The patient underwent a left radical nephrectomy, an inferior vena cava thrombectomy, and a saddle embolectomy. Histological examination of the mass and thrombus confirmed the diagnosis. He had an uneventful recovery and was discharged from the hospital.

RCC accounts for approximately 80% of all primary renal neoplasms, and commonly is termed the “internist’s tumor.” Hematuria is the most common symptom. It is accompanied by flank pain and a palpable abdominal mass in less than 15% of cases.1 Diagnosis of RCC is often made late due to delayed clinical presentation and 20% of patients have metastatic disease at initial diagnosis.2 PE due to tumor thrombus as an initial manifestation of RCC is rare, but is a well-recognized entity leading to dyspnea, pleuritic chest pain, hypoxemia, and—in severe cases—acute cor pulmonale with hemodynamic failure.3-5

Staging CT is required in patients with suspected RCC, and MRI is needed, with transesophageal echocardiography used adjunctively, to evaluate cephalic thrombus extension when indicated.6 IVC tumor thrombus occurs in 4%-10% of all cases, most often originating in the renal vein and extending cranially, subsequently propagating to the lungs.7 Survival in local non-metastatic disease with IVC thrombus is no different whether renal vein extension occurs or not, and ranges from 40%-69%, following surgical resection and thrombectomy.8 In those with distant metastases who require venal caval thrombectomy, five-year survivals range from 0%-12.5%.2

The first case of successful removal of a PE secondary to RCC was documented in 1977.1 The goal of surgery is tumor resection and prevention of recurrent embolic events. It is the only effective means of improving survival in the presence of intravascular tumor. Preoperative anticoagulation may be warranted in patients who present with PE, but should be discontinued following definitive surgical treatment secondary to increased risks of hemorrhage.8 TH

References

1. Daughtry JD, Stewart BH, Golding LAR, Groves LK. Pulmonary embolus presenting as the initial manifestation of renal cell carcinoma. Ann Thorac Surg. 1977;24:178-181.
2. Goetzl MA, Goluboff ET, Murphy AM, et al. A contemporary evaluation of cytoreductive nephrectomy with tumor thrombus: morbidity and long term survival. Urol Oncol. 2004; 22:182-187.
3. Kubota H, Furuse A, Kotsuka Y, et al. Successful management of massive pulmonary tumor embolism from renal cell carcinoma. Ann Thorac Surg. 1996;61:708-710.
4. Gayer G, Mini S, Olchovsky D, et al. Pulmonary embolism—the initial manifestation of renal cell carcinoma in a young woman. Emerg Radiol. 2003;10:43-45.
5. Eggener SE, Dalton DP. Bilateral pulmonary artery tumour emboli from renal carcinoma. Lancet Oncol. 2004;5:173.
6. Tsuji Y, Goto A, Hara I, et al. Renal cell carcinoma with extension of tumor thrombus into vena cava: Surgical strategy and prognosis. J Vasc Surg. 2001;33:789-796.
7. Zisman A, Pantuck AJ, Chao DH, et al. Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate? J Urol. 2002;168:962-967.
8. Nesbitt JC, Soltero ER, Dinney CPN, et al. Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus. Ann Thorac Surg. 1997;63:1592-1600.

A48-year-old male presents with three weeks of worsening shortness of breath and pleuritic chest discomfort. A week before the onset of these symptoms, he noticed increasing fatigue, weight loss, abdominal discomfort, and persistent hematuria He was otherwise healthy and was taking no medications.

Physical examination reveals a tachypneic yet hemodynamically stable patient, with left upper quadrant fullness. CT chest and abdomen, reveal the following (see right).

You suspect that this finding is secondary to an extrapulmonary process. What unifying diagnosis most likely accounts for these findings? What is your diagnosis?

1. Antiphospholipid syndrome
2. Antithrombin III deficiency
3. Renal cell carcinoma
4. Protein C deficiency
5. Prostate carcinoma

Discussion

The answer is C: Renal cell carcinoma (RCC) with caval extension causing PE; this suggests that the PE was due to tumor thrombus. The photo on p. 8 shows areas of increased attenuation in the prominent right and left pulmonary arteries, consistent with a saddle pulmonary embolism. An MRI of the abdomen (see photo above) reveals a large left renal mass extending to Gerota’s fascia and into the left renal vein, protruding slightly into the inferior vena cava (IVC).

The MRI demonstrates an occlusive thrombus in the left renal vein with propagation into the inferior vena cava. The patient underwent a left radical nephrectomy, an inferior vena cava thrombectomy, and a saddle embolectomy. Histological examination of the mass and thrombus confirmed the diagnosis. He had an uneventful recovery and was discharged from the hospital.

RCC accounts for approximately 80% of all primary renal neoplasms, and commonly is termed the “internist’s tumor.” Hematuria is the most common symptom. It is accompanied by flank pain and a palpable abdominal mass in less than 15% of cases.1 Diagnosis of RCC is often made late due to delayed clinical presentation and 20% of patients have metastatic disease at initial diagnosis.2 PE due to tumor thrombus as an initial manifestation of RCC is rare, but is a well-recognized entity leading to dyspnea, pleuritic chest pain, hypoxemia, and—in severe cases—acute cor pulmonale with hemodynamic failure.3-5

Staging CT is required in patients with suspected RCC, and MRI is needed, with transesophageal echocardiography used adjunctively, to evaluate cephalic thrombus extension when indicated.6 IVC tumor thrombus occurs in 4%-10% of all cases, most often originating in the renal vein and extending cranially, subsequently propagating to the lungs.7 Survival in local non-metastatic disease with IVC thrombus is no different whether renal vein extension occurs or not, and ranges from 40%-69%, following surgical resection and thrombectomy.8 In those with distant metastases who require venal caval thrombectomy, five-year survivals range from 0%-12.5%.2

The first case of successful removal of a PE secondary to RCC was documented in 1977.1 The goal of surgery is tumor resection and prevention of recurrent embolic events. It is the only effective means of improving survival in the presence of intravascular tumor. Preoperative anticoagulation may be warranted in patients who present with PE, but should be discontinued following definitive surgical treatment secondary to increased risks of hemorrhage.8 TH

References

1. Daughtry JD, Stewart BH, Golding LAR, Groves LK. Pulmonary embolus presenting as the initial manifestation of renal cell carcinoma. Ann Thorac Surg. 1977;24:178-181.
2. Goetzl MA, Goluboff ET, Murphy AM, et al. A contemporary evaluation of cytoreductive nephrectomy with tumor thrombus: morbidity and long term survival. Urol Oncol. 2004; 22:182-187.
3. Kubota H, Furuse A, Kotsuka Y, et al. Successful management of massive pulmonary tumor embolism from renal cell carcinoma. Ann Thorac Surg. 1996;61:708-710.
4. Gayer G, Mini S, Olchovsky D, et al. Pulmonary embolism—the initial manifestation of renal cell carcinoma in a young woman. Emerg Radiol. 2003;10:43-45.
5. Eggener SE, Dalton DP. Bilateral pulmonary artery tumour emboli from renal carcinoma. Lancet Oncol. 2004;5:173.
6. Tsuji Y, Goto A, Hara I, et al. Renal cell carcinoma with extension of tumor thrombus into vena cava: Surgical strategy and prognosis. J Vasc Surg. 2001;33:789-796.
7. Zisman A, Pantuck AJ, Chao DH, et al. Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate? J Urol. 2002;168:962-967.
8. Nesbitt JC, Soltero ER, Dinney CPN, et al. Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus. Ann Thorac Surg. 1997;63:1592-1600.

A48-year-old male presents with three weeks of worsening shortness of breath and pleuritic chest discomfort. A week before the onset of these symptoms, he noticed increasing fatigue, weight loss, abdominal discomfort, and persistent hematuria He was otherwise healthy and was taking no medications.

Physical examination reveals a tachypneic yet hemodynamically stable patient, with left upper quadrant fullness. CT chest and abdomen, reveal the following (see right).

You suspect that this finding is secondary to an extrapulmonary process. What unifying diagnosis most likely accounts for these findings? What is your diagnosis?

1. Antiphospholipid syndrome
2. Antithrombin III deficiency
3. Renal cell carcinoma
4. Protein C deficiency
5. Prostate carcinoma

Discussion

The answer is C: Renal cell carcinoma (RCC) with caval extension causing PE; this suggests that the PE was due to tumor thrombus. The photo on p. 8 shows areas of increased attenuation in the prominent right and left pulmonary arteries, consistent with a saddle pulmonary embolism. An MRI of the abdomen (see photo above) reveals a large left renal mass extending to Gerota’s fascia and into the left renal vein, protruding slightly into the inferior vena cava (IVC).

The MRI demonstrates an occlusive thrombus in the left renal vein with propagation into the inferior vena cava. The patient underwent a left radical nephrectomy, an inferior vena cava thrombectomy, and a saddle embolectomy. Histological examination of the mass and thrombus confirmed the diagnosis. He had an uneventful recovery and was discharged from the hospital.

RCC accounts for approximately 80% of all primary renal neoplasms, and commonly is termed the “internist’s tumor.” Hematuria is the most common symptom. It is accompanied by flank pain and a palpable abdominal mass in less than 15% of cases.1 Diagnosis of RCC is often made late due to delayed clinical presentation and 20% of patients have metastatic disease at initial diagnosis.2 PE due to tumor thrombus as an initial manifestation of RCC is rare, but is a well-recognized entity leading to dyspnea, pleuritic chest pain, hypoxemia, and—in severe cases—acute cor pulmonale with hemodynamic failure.3-5

Staging CT is required in patients with suspected RCC, and MRI is needed, with transesophageal echocardiography used adjunctively, to evaluate cephalic thrombus extension when indicated.6 IVC tumor thrombus occurs in 4%-10% of all cases, most often originating in the renal vein and extending cranially, subsequently propagating to the lungs.7 Survival in local non-metastatic disease with IVC thrombus is no different whether renal vein extension occurs or not, and ranges from 40%-69%, following surgical resection and thrombectomy.8 In those with distant metastases who require venal caval thrombectomy, five-year survivals range from 0%-12.5%.2

The first case of successful removal of a PE secondary to RCC was documented in 1977.1 The goal of surgery is tumor resection and prevention of recurrent embolic events. It is the only effective means of improving survival in the presence of intravascular tumor. Preoperative anticoagulation may be warranted in patients who present with PE, but should be discontinued following definitive surgical treatment secondary to increased risks of hemorrhage.8 TH

References

1. Daughtry JD, Stewart BH, Golding LAR, Groves LK. Pulmonary embolus presenting as the initial manifestation of renal cell carcinoma. Ann Thorac Surg. 1977;24:178-181.
2. Goetzl MA, Goluboff ET, Murphy AM, et al. A contemporary evaluation of cytoreductive nephrectomy with tumor thrombus: morbidity and long term survival. Urol Oncol. 2004; 22:182-187.
3. Kubota H, Furuse A, Kotsuka Y, et al. Successful management of massive pulmonary tumor embolism from renal cell carcinoma. Ann Thorac Surg. 1996;61:708-710.
4. Gayer G, Mini S, Olchovsky D, et al. Pulmonary embolism—the initial manifestation of renal cell carcinoma in a young woman. Emerg Radiol. 2003;10:43-45.
5. Eggener SE, Dalton DP. Bilateral pulmonary artery tumour emboli from renal carcinoma. Lancet Oncol. 2004;5:173.
6. Tsuji Y, Goto A, Hara I, et al. Renal cell carcinoma with extension of tumor thrombus into vena cava: Surgical strategy and prognosis. J Vasc Surg. 2001;33:789-796.
7. Zisman A, Pantuck AJ, Chao DH, et al. Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for advanced disease associated with an increased complication rate? J Urol. 2002;168:962-967.
8. Nesbitt JC, Soltero ER, Dinney CPN, et al. Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus. Ann Thorac Surg. 1997;63:1592-1600.