The XVth International Symposium on Amyloidosis

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The XVth International Symposium on Amyloidosis

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INTERNATIONAL SOCIETY OF AMYLOIDOSIS

The XVth International Symposium on Amyloidosis UPPSALA 3–7 July 2016

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2016-06-14 10:14

PB70 INTRACTABLE, INOPERABLE, RAPIDLY FATAL κ-CHAIN AL AMYLOIDOSIS, WITH BASOLINGUAL INVOLVEMENT, COMPROMISING RESPIRATION AND DIGLUTITION A Symeonidis1, V Lazaris1, DI Papachristou2, V Labropoulou1, P Triantafyllou1, E Tzouvara1, M Tiniakou1, A Kourakli1. Hematology Division, Dept of Int. Medicine1, and Dept of Anatomy-Histology & Embryology2, University of Patras, Medical School, Patras, Greece. INTRODUCTION: We describe an unusually severe case of non-cardiac, non-renal AL amyloidosis/ amyloidotic myeloma, in a 66-year old female patient, with progressive clinical course, despite a favourable response to fisrt-line treatment. PATIENT AND METHODS: This patient reported a previous history of Hashimoto’s thyroiditis-hypothyroidism, and had an otherwise unremarkable previous history. Four months before her admission, she manifested a rapidlyprogressing, sublingual-submandibular engorgement, initially considered as a thyroid nodule, but associated with voice changes, tiredness on speech and swallowing disturbances. The patient was hospitalized in the ENT department, and a severe tumorous engorgement of the whole tongue was noticed, following a facial MRI. A biopsy from the basal lingual part revealed deposition of amorphous or slightly fibroid eosinophilic material, which, with the Congo-red staining was strongly positive. RESULTS: She was referred to our Department with a probable diagnosis of amyloidosis. She was only capable to intake liquid foods. On admission she was anemic (Hb 9.8 g/dl), with moderate leukocytosis-neutrophilia (absolute numbers 12.8 x 109/l and 9.2 x 109/l, respectively) and thrombocytosis (582 x 109/l). Her serum LDH was elevated and serum protein electrophoresis revealed an IgG-kappa M-component. Serum IgG was measured 16.7 g/l, with severe immunoparesis of IgA and IgM (0.08 and 0.07, g/l respectively). Serum free kappa chain was 1530 mg/dl and lampda 5.8 mg/dl (κ/λ ratio 263.8). A 24-hour urine sample disclosed 22.1 gr of kappa chain and 0.055 gr of lampda chain (κ/λ ratio 4018). Her cardiac ultrasound showed normal findings, however, NT-proBNP level was found increased 1127 pg/ml. Her bone marrow examination revealed a diffuse infiltration of abnormal plasma cell population, at about 45%, and the trephine biopsy demonstration κ-light chain- and Congo-red staining positivity, thus confirming the diagnosis of amyloidotic myeloma. She did not complain for bone symptoms and a complete skeletal survey did not reveal lytic lesions. A spinal MRI however, disclosed some findings of myelomatous vertebral involvement. She was treated with the combination of cyclophosphamide-bortezomib and dexamethasone (VCD) q/21 days, and following 3 cycles of treatment, although her serum M-component, IgG and free κ-chain levels were substantially improved, she exhibited dramatic clinical deterioration. She was completely incapable to receive any kind of food, and thus a gastrostomy was performed, to maintain feeding and hydration. Again ENT surgeons considered any surgical intervention unattainable or life-threatening. Soon thereafter, she started to experience inspiratory dyspnea and a treacheostomy was also performed. She then manifested recurrent respiratory and systemic infections from gram+ and gram- microorganisms and she gradually developed renal and respiratory failure, and finally succumbed, with an overall survival of 12 weeks following initial diagnosis or 7 months from the initiation of her disease-related symptoms. DISCUSSION-CONCLUSIONS: This abstract reports an unusually severe, intractable, inoperable, progressive, and ultimately fatal case of non-cardiac, non-renal, sublingual κ-chain, AL amyloidosis/amyloidotic myeloma, despite a favorable response to anti-myeloma treatment, and implies the need for combination antimyeloma and amyloiddetaching treatment, even in cases with presumably non ominous local consequences.

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ISA INTERNATIONAL SOCIETY OF AMYLOIDOSIS 2016

INTRACTABLE, INOPERABLE, RAPIDLY FATAL κ-CHAIN AL AMYLOIDOSIS, WITH BASOLINGUAL INVOLVEMENT, COMPROMISING RESPIRATION AND DEGLUTITION A

1 Symeonidis ,

V

1 Lazaris ,

DI

2 Papachristou ,

1 Labropoulou ,

1 Triantafyllou ,

1 Tzouvara ,

V P E 1 1 M Tiniakou , A Kourakli . 1 2 Hematology Division, Dept of Int. Medicine , and Dept of Anatomy-Histology & Embryology , University of Patras, Medical School, Patras, Greece. INTRODUCTION Systemic AL amyloidosis, not severely compromising cardiac or renal function, but presented with mainly other tissue involvement may have a relatively long clinical course and survival. The tongue is an organ commonly affected by the deposition of amyloid. Amyloidosis of the tongue is usually presented with tongue enlargement (macroglossia) as well as with focal amyloidotic deposits, sometimes in visually prominent areas, and very rarely compromises swallowing and deglutition We describe an unusually severe case of non-cardiac, non-renal AL amyloidosis/ amyloidotic myeloma, in a 66-year old female patient, with progressive clinical course, and ultimately fatal outcome, despite a favorable response to first-line anti-myeloma treatment.

CASE DESCRIPTION This patient reported an otherwise unremarkable previous history, except for Hashimoto’s thyroiditis-hypothyroidism. - Four months before her admission, she manifested a rapidly-progressing, indolent, hard sublingual-submandibular engorgement, initially considered as a thyroid nodule, but associated with:  voice changes and tiredness on speech  taste- and swallowing disturbances The patient was hospitalized in the ENT department, and a severe tumorous engorgement of the whole tongue was noticed, following a facial MRI (see Figure 1, 3 and 4). - A biopsy from the basal lingual part revealed deposition of amorphous or slightly fibroid eosinophilic material, which, with the Congo-red staining was strongly positive. - Serum protein electrophoresis revealed a small M-component, which with immunofixation it was identified as IgG/κ. - A 99Tc bone scan revealed diffuse areas of radionucleide uptake outside the bone tissue, at both shoulders and at many sternoclavicular, pleurovertebral and lumbar joints, as well as at the iliosacral joint. Results were interpreted as typical of the suspected amyloidosis. She was then referred to our Department for further evaluation, with a probable diagnosis of amyloidosis. On admission she was only capable to intake liquid foods. - She was anemic (Hb 9.8 g/dl), with moderate leukocytosis-neutrophilia (absolute numbers 12.8 x 109/l and 9.2 x 109/l, respectively) and thrombocytosis (582 x 109/l). - Her serum LDH was elevated at 289 IU (normal – 230 IU) and serum albumin decreased 28 g/l. - On serum protein electrophoresis an IgG/κ M-component of 1.26 g/l was revealed. - Serum IgG was 16.7 g/l, with severe immunoparesis (IgA 0.08 and IgM 0.07 g/l). Serum free kappa chain was 15.3 g/l and lampda 0.058 g/l (κ/λ ratio: 263.8). - A 24-hour urine sample disclosed 22.1 gr of kappa chain and 0.055 gr of lampda chain (κ/λ ratio: 401.8). - Her cardiac ultrasound showed normal findings, without any finding reminiscent of amyloidosis, however, serum NT-proBNP level was found increased at 1127 pg/ml. - Her bone marrow examination revealed a diffuse infiltration of abnormal monoclonal plasma cell population, of about 45%, and the trephine biopsy demonstrated κ-light chain- and Congo-red staining positivity, thus confirming the diagnosis of amyloidotic myeloma. - An endocrinologic survey revealed hypothyroidism of central type and suggested investigation of posterior hypophysis function, with a probability of hypophyseal amyloidosis. However, the patient was incapable to undergo the dynamic tests of posterior hypophysis function. - She did not complain for bone symptoms and a complete skeletal survey did not reveal lytic lesions. A spinal MRI however, disclosed some findings of myelomatous vertebral involvement (see Figures 1 and 3). - She was treated with the combination of cyclophosphamide-bortezomib and dexamethasone (VCD) q/21 days, and following 3 cycles of treatment, although her serum M-component and immunoglobulin levels were substantially improved (IgG 4.34, IgA 0.28, IgM 0.25, κ-chains 0.74 λ-chains 0.079, κ/λ ratio 9.4), demonstrating a VGPR of the myeloma, as did also urine light chains (κ: 0.88, λ: 0.062, κ/λ: 14.2) she exhibited dramatic clinical deterioration. - She was completely incapable to receive any kind of food, and thus a gastrostomy was performed, to maintain feeding and hydration (see Figure 2). - Again ENT surgeons considered any surgical intervention unattainable or life-threatening. - She needed and was provided psychological support. - Soon thereafter, she started to experience inspiratory dyspnea and a treacheostomy was also performed. Moreover, despite the careful balance of liquid and electrolyte homeostasis and feeding via gastrostomy her condition steadily deteriorated. - She manifested recurrent respiratory and systemic infections from gram(+) and gram(-) microorganisms and she gradually developed renal and respiratory failure, and finally succumbed, with an overall survival of 12 weeks following initial diagnosis or 7 months from the initiation of her disease-related symptoms, without the manifestation of any degree of cardiac dysfunction.

Figure 1. Facial MRI reveals global engorgement of the tongue, with compression of the hypopharynx and the epiglottis. The basal part of the tongue appears to have amorphous areas with different tissue density and is protruded at the submandibular area.

Figure 4. Cross-sectional MRI of the submandibular area, showing thickness of the basal area of the tongue with deposition of amorphous material (arrow).

Figure 2. Clinical presentation of the patient, following two cycles of the VCD regimen. Despite the substantial laboratory improvement she remains critically ill, incapable to eat and swallow, barely receiving liquids. Three weeks later she had to undergo gastrostomy and tracheostomy.

Figure 3. Facial MRI – lateral view. Formation of tumorous deposition from amorphous material of light opacity at the basal area of the tongue. Similar depositions are obvious at the muscular area and the subcutaneous tissue of the back (white arrows).

DISCUSSION

Systemic AL amyloidosis is a severe, life-threatening disease, particularly when it primarily affects the myocardium. In this situation prognosis is dismal, and the median survival is only a few months. Renal amyloidosis may also compromise renal function, although in such cases, when the disease is put under control prognosis is better and survival may be extended. We herein report an unusually severe, intractable, inoperable, progressive, and ultimately fatal case of non-cardiac, non-renal, sublingual κ-chain, AL amyloidosis/amyloidotic myeloma, despite a favorable response to antimyeloma treatment. The disease at presentation was generalized with obvious bonejoints and subcutaneous involvement and a severe probability of hypophyseal involvement, manifested as hypothyroidism of central type, although this was not proved. Our patient, although responded favorably to systemic antimyeloma treatment with the VCD regimen, and her serum IgG and the free serum and urine light chains were reduced by >90%, she was steadily deteriorating due to the systemic deposition disease. This case implies that even when cardiac involvement is not the major clinical manifestation of systemic Al amyloidosis, in cases of multiple tissue- and organ involvement, a combination of both, antimyeloma and amyloid-detaching treatment, may be necessary, to reverse the devastating clinical consequences of the disease, even in cases with presumably non ominous local consequences. Therefore, such combined treatment approaches should be designed and tested in multicenter clinical trials. REFERENCES 1. 2. 3. 4. 5.

Babburi S et al: J Clin Diagn Res 2013; 7: 3094-3095 Liakou C et al: Case Reports in Medicine 2016; Article ID 6723575, 3 pages Yuda S et al: Intern Med 2015; 54: 1833-1840. Thibault I et al: Case Reports in Oncology 2011; 4: 392-399. Hammami B et al: Europ. Ann. Otolar. Head Neck Dis. 2010; 127: 83-85.