CME INDIA Case Presentation by Dr. Ashutosh Dubey, DNB Med, Specialist – Internal Medicine, Hindalco Hospital, Renukut (UP).
CME INDIA Case Study
Quick Take Away
| If you get a patient with a rugose-textured and uneven tongue which mimics atrophy, consider macroglossia caused by amyloidosis and examine the tongue hardness. |
| Macroglossia has been very rarely reported as a first clinical sign of multiple myeloma. |
| If you are a dermatological and venereal diseases specialist you can contribute to early diagnosis of Multiple Myeloma with a complaint of tongue enlargement. |
A 63-year-old male presented with:
- Thickened voice along with Enlarged tongue
- Decreased mouth opening
- Unable to eat food for past 6 months
- Dark pigmented pruritic rashes diffusely distributed over chest, back and extremities for 4 months.
- No associated chest pain, SOB, fever, cough, urine discolouration, limb pain, frothing of urine, fever, Abdominal pain etc.
- Known case of HTN, CAD.
- No H/O DM, Thyroid disorder, Substance abuse etc.
What was found on examination?
- Tongue was grossly enlarged with teeth indentation along the margin, decreased mouth opening with thickened voice.
- Hyperpigmented macular rashes was seen evenly distributed over extremities, chest and back.
- Other general and systemic examination – normal.
Routine Lab Findings
- Raised TSH 9.85
- Raised serum Total Protein 8.5
- PBS – Macrocytic Anaemia
- ESR 99
- MCV 96
- USG W/A – enlarged prostate with Rt renal calculus
- CT Brain – NAD
- Raised Sr Calcium 11.4
- Low Hb 8.6
- Serum Electrophoresis was done showing M Spike
Provisional Diagnosis
Amyloidosis and Multiple Myeloma
Further Investigations
- Raised B2 Microglobulin.
- Serum Immunofixation – IgG Lambda type Monoclonal protein.
- Serum Electrophoresis – M band in gamma region.
- BM Aspirate – Marrow smears show an increased presence of plasma cells; constituting approximately 80% of total nucleated cells. Some atypical plasma cells with high nucleo-cytoplasmic ratio, occasional prominent nucleoli are seen. Myeloid and erythroid series of cells are relatively reduced.
- FISH analysis is POSITIVE for gain/amplification of chromosome region 1q21 (in 29% of the cells). FISH analysis is NEGATIVE for TP53 gene deletion, deletion of chromosome region 1p32, and IgH gene rearrangement.
Patient is on chemotherapy and is under follow up.
CME INDIA Case Discussion:
Dr. Dibyendu Dey, DM, Heamatologist, Balco Medical Centre, Raipur:
- The reports and patient characteristics fit into multiple myeloma, an aggressive one, with 80% plasma cell in bone marrow.
- There are few points to look into to rule out amyloidosis. Macroglossia, skin pigmentation are soft points towards amyloidosis.
- Other points to look into:
- Hepatosplenomegaly.
- Enlarged kidney, non-oliguric renal failure.
- Restrictive cardiomyopathy, septal enlargement, diastolic heart failure.
- Peripheral neuropathy.
- Thyroid disorder, skin pigmentation, racoon eye pigmentation.
- Bone marrow, abdominal fat pad, omental biopsy, rectal biopsy for special stain for amyloidosis. (Congo red staining) nerve biopsy or cardiac biopsy can be done.
- The treatment is triplet therapy with bortezomib, lenalidomide and dexamethasone followed by autologous BMT.
- If high risk/ amyloidosis, can add monoclonal anti CD 38 Daratumumab with the triplet therapy. Though controversial to use as first line, as it is costly and add marginal benefit to high-risk patient only.
Another potential differential diagnosis can be POEMS syndrome.
The components of the syndrome are:
- Polyneuropathy
- Organomegaly: hepatomegaly, splenomegaly or lymphadenopathy
- Endocrinopathy: diabetes, thyroid disorder or parathyroid disorder, hypogonadism
- M band
- Skin manifestation: hypo or hyperpigmentation, hypertrichosis, telengiectasua
Other features are:
- Volume overload: oedema, ascites, clubbing,
- Hematologic: polycythemia, thrombocytopenia
- sclerotic (not lytic) bone lesion,
- Castleman disease
- Biochemical: increased VEGF
Dr. Nilanjan Sinha, Haematologist Physician, Kolkata:
- Beautiful picture of macroglossia.
- A case of multiple myeloma (Ig G, Lambda) with secondary AL amyloidosis.
- Along treatment of myeloma an abdominal fat pad biopsy for Congo red stain or Congo red stain on bone marrow biopsy is suggested.
- Also, nT-proBNP and an Echocardiography is suggested.
Dr. Dibyendu Dey, Heamato Balco Medical Centre, Raipur:
- Is macroglossia is first presentation? Most of the time the initial symptoms are missed by patient and doctor alike. In this patient, also lot of other clinical and biochemical manifestation are there. Like Altered Alb: glob ratio, hypercalcemia, skin pigmentation.
- Need to find whether classical symptoms of myeloma were there or not, namely bone pain, anaemia, pedal oedema, repeated infection, etc.
- We see lot of patients on treatment with nephrologist for renal failure or orthopaedics for low back pain, ultimately diagnosed as myeloma. Need to keep it in differential diagnosis to rule out myeloma
- Amyloidosis is also very difficult to pinpoint early because of multiple organ system involvement requiring multidisciplinary approach.
- It is very difficult to say, that a patient with 80 % bone marrow plasma cell would not have any lytic lesion or nephropathy.
Dr. Sanjeev, Haematologist, SGPGI, Lucknow:
- Macroglossia is a feature of associated Secondary Amyloidosis, usually Multiple myeloma don’t have macroglossia, can be confirmed with FAT pad biopsy, rectal biopsy, must look for associated cardiac amyloid, by doing scan & Sr BNP level, Renal amyloid by doing renal biopsy.
- Such patients don’t do well, compared to patients with Multiple myeloma without Sec AL amyloid.
- Cutaneous amyloid deposits can be demonstrated by skin biopsy.
CME INDIA Learning Points
- Macroglossia has been very rarely reported as a first clinical sign of multiple myeloma.
- Amyloidoses are rare diseases characterized by extracellular aggregation of at least 31 different amyloid proteins.
- Diagnosis of amyloidosis depends on histopathological examination.
- In routine hematoxylin-eosin staining, homogeneous eosinophilia is observed.
- Amyloid protiens also react with Congo red stain and yield reflection under polarized microscopy.
- Amyloid-proteinaceous materials have various effects on cellular level.
- Amyloid proteins may accumulate in various internal organs, particularly in the heart and kidneys and also in the tongue.
- Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis. In this condition, culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells.
- AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained
CME INDIA Tail Piece
- The term “macroglossia” defines a painless and long-term tongue enlargement, which can be recognized by observation of a resting tongue protruding over the dentoalveolar structures.
- Macroglossia is classified into two major categories:
- True- macroglossia – True macroglossia is associated with definitive histological changes in the tongue and it is frequently observed due to hypertrophy of the tongue muscles or due to infiltration of normal tissue with abnormal proteins or glycogen.
- Pseudo-macroglossia – Pseudomacroglossia refers to a normal-sized but large-appearing tongue. This condition is usually a result of the anatomical abnormalities of the oral cavity.
- Fluorescence in situ hybridization (FISH): It is a laboratory technique for detecting and locating a specific DNA sequence on a chromosome.
- Multiple Myeloma (MM) belongs to a family of neoplasms involving clonal expansion of immunoglobulin secreting B-cells, often with bone marrow involvement, resulting in anemia and leukopenia. This FISH panel is designed to detect the most common, and/or prognostically-significant abnormalities in Multiple Myeloma and related plasma cell neoplasms.
References:
- Muchtar E, Buadi FK, Dispenzieri A, Gertz MA. Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy. Acta Haematol. 2016;135(3):172-90. doi: 10.1159/000443200. Epub 2016 Jan 16. PMID: 26771835.
- Demirkan S, Şavk E, Alp A, Doger FK, Kadikoylu G, Gunduz O. Macroglossia as a presenting feature of multiple myeloma. J Family Med Prim Care. 2017;6(1):146-147. doi:10.4103/2249-4863.214968
- Murthy P, Laing MR. Macroglossia. BMJ. 1994;309:1386–7
- Yumi Murakami,Genya Watanabewt al. Atypical macroglossia caused by multiple myeloma-associated systemic amyloidosis with severe lingual movement disorder and tongue sclerosis. 24 October 2020 https://doi.org/10.1111/ncn3.12464
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Though macroglossia as a presentation of Multiple Myeloma, is uncommon, it’s not rare. In fact, one case of multiple Myeloma with macroglossia,presented in the clinical meeting in Medical college ,Calcutta.
The predominant abnormal paraprotien was lamda light chain, so diagnosis is obvious. O
The getting biopsy in this case may dangerous, as it may induce profuse bleeding and I have been able to see at least one case who bled to death after renal biopsy in a case of multiple Myeloma.
Now, in 2022,imaging is the method of choice in multiple Myeloma
Thanks
Thanks sir for your input.
Macroglossia is mostly a part of amyloidosis associated with multiple myeloma. Most of these amyloidosis are lambda restricted. So, when lambda restriction is found, it is prudent to identify amyloidosis.
The treatment approach and prognosis changes if amyloidosis is there
One important finding of excessive bleeding may be due to factor X deficiency associated with amyloidosis. So pre biopsy PT, APTT testing and appropriate fresh frozen plasma replacement may minimize such complication.