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. 2025 Mar;30(1):e12680.
doi: 10.1111/jns.12680.

Minimal invasive biopsies are highly sensitive for amyloid detection in hereditary transthyretin amyloidosis with polyneuropathy

Luca Leonardi  1   2 , Clovis Adam  1   3   4 , Guillemette Beaudonnet  1   5 , Diane Beauvais  1 , Cécile Cauquil  1 , Adeline Not  1 , Olivier Morassi  1 , Olivier Trassard  4 , Andoni Echaniz-Laguna  1   3 , David Adams  1   3 , Céline Labeyrie  1   3   4
Affiliations

Minimal invasive biopsies are highly sensitive for amyloid detection in hereditary transthyretin amyloidosis with polyneuropathy

Luca Leonardi et al. J Peripher Nerv Syst. 2025 Mar.

Abstract

Objective: To assess the effectiveness of labial minor salivary gland biopsy (LSGB) alone or in combination with punch skin biopsy (SB) for the detection of amyloid deposits in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Methods: In this single-center retrospective study, Congo red staining of minimal invasive LSGB (4 mm) and SB (3 mm) was assessed in ATTRv-PN patients consecutively evaluated between 2012 and 2023.

Results: Histopathological data of 171 ATTRv-PN, including 49 early-onset p.Val50Met, 58 late-onset p.Val50Met, and 64 non-p.Val50Met, were reviewed. LSGB and SB identified amyloid deposits in 123/171 (72%) and 131/171 (77%) patients respectively (p = 0.2). Combining LSGB and SB increased the amyloid detection rate to 150/171 (88%), especially in late-onset p.Val50Met (48/58 [83%]) and non-p.Val50Met patients (55/64 [86%]). LSGB and SB have a similar rate of detection of amyloid depositions in early onset p.Val50Met patients (94%). Also, the LSGB/SB combination identified amyloidosis in 89% (55/62) of early-stage ATTRv-PN patients.

Conclusions: In our study, combining LSGB and SB allowed the detection of amyloid deposits in 88% of ATTRv-PN patients. LSGB/SB analysis may be of major interest to confirm entry in the disease at very early-stage ATTRv-PN, with implications in disease-modifying treatment initiation.

Keywords: amyloid deposition; hereditary transthyretin amyloidosis; labial salivary gland biopsy; polyneuropathy; skin biopsy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The pathological pattern of amyloid deposits in Labial salivary gland biopsy. (A, E, I) hematoxylin–eosin–Safran staining; (B, F, J) Congo red staining; (C, G, K) Immunostaining with anti‐TTR antibody. (D) Pathological pattern of amyloid deposit in skin biopsy. (A, B, C) p.Val50Met early onset LSGB showing diffuse amyloid deposits (black arrows) around acini, ducts, and adipocytes not affecting vessels (blue asterisks). (E, F, G) Val30Met late‐onset LSGB showing thin amyloid deposits (black arrows) around adipocytes. (I, J, K) p.Val142Ile LSGB showing bulky perivascular amyloid deposits (black arrows). (D) Congo red staining of p.Val50Met early onset skin biopsy showing diffuse dermal amyloid deposits (black arrow). (H) Minimally invasive procedure for LSGB. (L) Minimally invasive procedure for skin biopsy.
FIGURE 2
FIGURE 2
Recommendations for minimally invasive biopsies for amyloid deposition detection in newly symptomatic mPND1A (A) and overt (B) ATTRv‐PN. EO, early onset; LO, late onset; LSGB, labial minor salivary gland biopsy; SB, skin biopsy.
See this image and copyright information in PMC

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Supplementary concepts