interesting case

1. Pink façade –
Unmasking misfolded
fibrillary protein
DR. JANANI MATHIALAGAN
3RD YEAR POST GRADUATE
DEPT OF PATHOLOGY

2. A 55 yr old male presented with
complaints of
Difficulty in swallowing solid food for 4 months
Associated with indigestion
No history of abdominal pain/ loose stools/ vomiting
No history of diabetes and hypertension
Barium swallow – normal findings
Serology – Negative
Patient also had multiple skin lesions in forehead and hence
Dermatology opinion was sought.
Patient was subjected to upper gastrointestinal endoscopy

3. Upper GI endoscopy
Superficial ulcerations and inflamed
mucosa in the antrum
Duodenum shows mucosal oedema

4. Lamina propria is
replaced by
eosinophilic
homogenous deposits.

5. Multiple blood vessels
surrounded by perivascular
eosinophilic deposit.

6. Impression
Features are of gastrointestinal amyloidosis

7. Patient also had
hyperpigmented
velvety plaque and
shiny papules over
forehead.

8. Clinical differential diagnosis:
Acanthosis nigricans
scleromyxedema
cutaneous amyloidosis
pseudolymphoma
Kimura disease

9. Homogenous
eosinophilic
deposits in
dermal-epidermal
junction

10. Eosinophilic deposits seen
around eccrine coils in
dermis.

11. Impression
Features are of cutaneous amyloidosis.

12. Eosinophilic deposits
other than amyloid
GIT
Collagenous
gastroenteritis
Bands of collagen in
submucosa +
lymphoplasmacytic
infiltrates
Massons trichrome
Systemic sclerosis
Sub-mucosal fibrosis
+ skin lesion
Massons trichrome
SKIN
Morphea
Elastic bundles +
perivascular
lymphocytic
infiltrates
Van Gieson
Cutaneous
mucinosis
mucin + fibroblasts +
fibrosis
Alcian blue

13. In view of multiple organ involvement of amyloidosis, further
evaluation was suggested to rule out plasma cell dyscrasias.
Patient came for review a month later to Dermatology and was
referred to General Medicine for complete workup.

14. Clinical examination
Pallor +
No evidence of icterus/ cyanosis/ clubbing/ lymphadenopathy/ oedema
Systemic Examination:
Oral cavity - Macroglossia
Neck - Purpuric lesions
CVS - S1 S2
RS - Normal vesicular breath sound
CNS - No focal neurological deficit
PA - Soft, non-tender

15. Macroglossia Purpuric lesions over neck

16. Lab investigations
CBC Hb – 9.9 g/dl (Reduced)
Peripheral smear Normocytic normochromic anaemia
Urea and creatinine Normal
24hr urine protein 189 mg/24hrs (Mildly elevated)
Urine Bence Jones protein Negative
Serum Calcium 6.8mg/dl (Reduced)
Serum protein electrophoresis M band positive
2D Echo Grade 2 diastolic dysfunction
NT-pro BNP 1159 pg/mL (Elevated)

17. X-ray of
skull

18. BONE MARROW IMPRINT

19. Marrow partly replaced by sheets of
plasma cells.
Plasma cells accounted for 65%.
BONE MARROW BIOPSY

20. Biopsy from bone marrow shows features of multiple myeloma.
Final impression –
Primary systemic amyloidosis with multiple myeloma.

21. Discussion

22. Amyloidosis
Extracellular deposition of misfolded beta fibrillary protein
Misnomer – mimicking amylose
Beta fibrillosis
Classified into
Systemic (Primary amyloidosis)
Localised (Medullary carcinoma thyroid)
Hereditary (Familial amyloidotic neuropathies)

23. Approach to amyloid deposits
Stains
Toluidine blue
Crystal violet
Thioflavine
Congo red with apple green birefringence under polarizing
microscope.
Elghetany, M.T. & Saleem, M.,Methods for staining amyloid in tissues: a review., Stain Technology, July
2014, pages 201-212.

24. Cutaneous amyloidosis
Causes:
Secondary to chronic inflammatory disease
Secondary to topical application of medicines
Secondary to autoimmune disease
Primary systemic amyloidosis
Gastrointestinal amyloidosis
Causes:
Primary
Familial

25. Multiple myeloma
Clonal malignant proliferation of the plasma cells
Criteria:
Clonal bone marrow plasma cells >10% / biopsy proven bony
or extramedullary plasmacytoma
+
Any one of the following
◦ Evidence of end organ damage – CRAB
◦ Clonal BM plasma cells 60% or more
◦ Involved: uninvolved serum free light chain ratio >/= 100
◦ 1 or more focal lesions in bone on MRI (size 5mm minimum)
International Myeloma Working Group (IMWG) Updated Criteria for the Diagnosis of Multiple Myeloma

26. Multiple myeloma
Clonal malignant proliferation of the plasma cells
Criteria:
Clonal bone marrow plasma cells >10% / biopsy proven bony
or extramedullary plasmacytoma
+
Any one of the following
◦ Evidence of end organ damage – CRAB
◦ Clonal BM plasma cells 60% or more
◦ Involved: uninvolved serum free light chain ratio >/= 100
◦ 1 or more focal lesions in bone on MRI (size 5mm minimum)
International Myeloma Working Group (IMWG) Updated Criteria for the Diagnosis of Multiple Myeloma

27. Multiple myeloma - End organ damage
defining event
CRAB
C: Calcium elevation (> 11 mg/dL or > 1 mg/dL higher than ULN)
R: Renal insufficiency (creatinine clearance < 40 mL/min or serum
creatinine > 2 mg/dL)
A: Anemia (Hb < 10 g/dL or 2 g/dL < normal)
B: Bone disease (≥ 1 lytic lesions on skeletal radiography, CT, or PET-
CT).
International Myeloma Working Group (IMWG) Updated Criteria for the Diagnosis of Multiple Myeloma

28. Multiple myeloma - End organ damage
defining event
CRAB
C: Calcium elevation (> 11 mg/dL or > 1 mg/dL higher than ULN)
R: Renal insufficiency (creatinine clearance < 40 mL/min or serum
creatinine > 2 mg/dL)
A: Anemia (Hb < 10 g/dL or 2 g/dL < normal)
B: Bone disease (≥ 1 lytic lesions on skeletal radiography, CT, or PET-
CT).
International Myeloma Working Group (IMWG) Updated Criteria for the Diagnosis of Multiple Myeloma

29. Why pink façade?
The initial clinical suspicion was of gastric carcinoma.
The underlying lesion (multiple myeloma) was unmasked by the lead
provided by the pink material in biopsy which was amyloid – beta
pleated sheets of misfolded protein.
Here, amyloid is the harbinger of multiple myeloma with primary
systemic amyloidosis which has a poorer prognosis than carcinoma
stomach and has a different treatment modality.
The deceiving nature (façade) of the pink material (Amyloid) in the
biopsy was the forerunner of plasma cell dyscrasia (Multiple myeloma).

30. Acknowledgements
Department of Medical Gastroenterology
Department of Dermatology
Department of General Medicine

31. Thankyou

32. Eosinophilic deposits
GIT
Collagenous
gastroenteritis
Bands of collagen in
submucosa +
lymphoplasmacytic
infiltrates
Massons trichrome
Systemic sclerosis
Sub-mucosal fibrosis +
skin lesion
Massons trichrome
SKIN
Morphea
Elastic bundles +
perivascular
lymphocytic infiltrates
Van Gieson
Cutaneous mucinosis
mucin + fibroblasts +
fibrosis
Alcian blue

33. Eosinophilic deposits
GIT
Collagenous
gastroenteritis
Bands of collagen in
submucosa +
lymphoplasmacytic
infiltrates
Massons trichrome
Systemic sclerosis
Sub-mucosal fibrosis +
skin lesion
Massons trichrome
Amyloid
Homogenous pink
deposits - junction and
perivascular/adnexal
Congo red
SKIN
Morphea
Elastic bundles +
perivascular
lymphocytic infiltrates
Van Gieson
Cutaneous mucinosis
mucin + fibroblasts +
fibrosis
Alcian blue

34. Cutaneous amyloidosis
Causes:
Secondary to chronic inflammatory disease
Secondary to topical application of medicines
Secondary to autoimmune disease
Primary systemic amyloidosis
Gastrointestinal amyloidosis
Causes: