Newly developed diffuse sclerosing papillary thyroid carcinoma during follow-up of benign thyroid nodules: a case report of two cases with ultrasound findings

Introduction

Diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is characterized by diffuse unilateral or bilateral involvement of PTC with extensive lymphatic invasion, dense stromal fibrosis, squamous metaplasia, numerous psammoma bodies, and background chronic lymphocytic thyroiditis. This subtype typically affects younger individuals, accounts for 0.7–6.6% of all PTCs and exhibits more aggressive behavior than classic PTC (S Pillai, et al. Crit Rev Oncol Hematol. 2015; 94:64–73).

Despite its distinct histopathological features, the sonographic diagnosis of DS-PTC remains challenging, with a reported accuracy of only 32.4% (B Kang, et al. Ann Surg Treat Res. 2025; 109:35–43). Most previously documented cases have been diagnosed at advanced stages, and limited information is available regarding the chronological progression of DS-PTC or its early imaging characteristics.

In this report, we present two rare cases of DS-PTC that emerged during long-term follow-up of patients initially diagnosed with benign thyroid tumors. We aimed to explore the ultrasonographic (US) features that preceded the pathological diagnosis, with particular emphasis on the appearance of multiple punctate echogenic foci (MPEF). We propose that MPEF may serve as a potential early sonographic indicator of DS-PTC development, offering insight into its preclinical evolution and aiding earlier detection.

Case 1

A 50-year-old woman presented with a slightly hypoechoic thyroid with a heterogeneous echotexture consistent with Hashimoto’s thyroiditis on ultrasound examination ([Fig. 1a]). Anti-thyroglobulin antibody (TgAb) was positive. A benign-looking nodule was present in the left lobe ([Fig. 1b, c]), and the findings remained unchanged for 35 months. 61 months after the initial visit, MPEF appeared in the right lobe ([Fig. 1d, e]) but was not observed in the left lobe ([Fig. 1f, g]). No findings suggestive of metastasis were found in the regional lymph nodes. Cytology of the right lobe revealed PTC. Total thyroidectomy with central lymph node dissection was performed. The resected thyroid showed an indistinct whitish area in the upper dorsal region of the right lobe ([Fig. 2a, b]) that corresponded to the MPEF site. Histology revealed typical DS-PTC in the right lobe ([Fig. 2c]), chronic thyroiditis throughout the thyroid, and lymph node metastases. The Ki-67 labeling index (LI) of the carcinoma cells was <5%.

Fig. 1 Case 1: a: Thyroid parenchyma is slightly hypoechoic with a heterogeneous echotexture (first visit). b and c: Benign-looking nodules are observed in the left lobe (first visit). d and e: Punctate echogenic foci (MPEF) are seen in the right lobe (61 months after first visit). f, g: No MPEF is observed in the left lobe (61 months after first visit). B-mode, longitudinal scan (a, b, d, f), transverse scan (c, e, g), Aplio 80 SSA-770A TOSHIBA PLT-805A probe 8 MHz (a–c), Aplio 500 TUS-A500 TOSHIBA PLT-1005BT probe 10 MHz (d–g).

Fig. 2 Case 1: The right lobe of the resected thyroid is larger than the left lobe (a). Cut surface is paler in color and slightly lobulated throughout (b: cut by the white line of [Fig. 2a]). The upper dorsal portion is more whitish (b, white arrow) and there are microscopically observed papillary thyroid carcinoma cells within dilated lymph vessels (c: hematoxylin and eosin-stained preparation, ×4).

Case 2

A 38-year-old woman had a nodule in the left lobe of her thyroid ([Fig. 3a]). The nodule was cytologically diagnosed as an oncocytic follicular neoplasm and remained unchanged during the 89 months of follow-up. However, another benign-looking nodule appeared in the right lobe ([Fig. 3b]). TgAb was positive. Nine months later, MPEF appeared throughout both bilateral lobes, except for the preexisting nodules ([Fig. 3c–f]). Moreover, an ill-defined low-echoic nodule with MPEF appeared in the lower portion of the right lobe ([Fig. 3g, h]) and was cytologically confirmed as PTC. Bilateral lymph nodes were suspected of having metastatic carcinoma. Total thyroidectomy was performed with lymph node dissections. The following three nodules were found ([Fig. 4a]): oncocytic adenoma (left lobe), follicular nodular disease (right upper), and classic PTC (right lower) ([Fig. 4b,c]). Non-nodular areas showed the appearance of DS-PTC associated with chronic thyroiditis. The Ki-67 LI was <5%. Metastatic PTC was found in central and bilateral lymph nodes.

Fig. 3 Case 2: a: A well-demarcated nodule is observed in the left lobe (first visit). b: A hypoechoic nodule is seen in the right lobe (89 months after first visit). c–f: Multiple punctate echogenic foci (MPEF) are seen throughout the thyroid except for the nodules (98 months after first visit). B-mode, longitudinal scan (a–c, e, g), transverse scan (d, f, h), Aplio 80 SSA-770A TOSHIBA PLT-805A probe 8 MHz (a, b), Aplio 500 TUS-A500 TOSHIBA PLT-1005BT probe 10 MHz (c–h).

Fig. 4 Case 2: Cut surface of resected thyroid shows diffusely paler background parenchyma and three nodules; follicular nodular disease (blue arrow), papillary thyroid carcinoma (white arrow), and oncocytic adenoma (black arrow) (a). Diffuse sclerosing papillary thyroid carcinoma is not present in oncocytic adenoma (black arrow) (b). Nodule marked with white arrow in [Fig. 4a] shows classic papillary thyroid carcinoma (c). (b: hematoxylin and eosin-stained preparation, ×2, c: hematoxylin and eosin-stained preparation, ×4).

Discussion

US findings of DS-PTC are characterized by an enlarged thyroid, heterogeneous background, MPEF, rich underlying flow signals, and lymph node metastasis (W Li et al. Orphanet J Rare Dis 2024; 19:136). Classic PTC may also be present (LD Thompson et al. Endocr Pathol 2005; 16:331–348). Among these findings, MPEF are the most characteristic, associated with numerous psammoma bodies diffusely distributed in the thyroid. MPEF were limited to one lobe in Case 1 and were observed in both lobes in Case 2.

DS-PTC is associated with chronic thyroiditis (LD Thompson et al. Endocr Pathol 2005; 16: 331–348). Thus, TgAb may be important for diagnosing this subtype. Both of our cases were associated with chronic thyroiditis, which existed before DS-PTC developed. Therefore, chronic thyroiditis may contribute to the development of DS-PTC as a precursor lesion rather than merely being a concurrent condition.

We found no case reports describing the development of DS-PTC. In our cases, DS-PTC developed during follow-up of benign nodules. In Case 2, the DS-PTC had spread throughout the thyroid in a short period of time, indicating that DS-PTC progression is extremely rapid compared with that of classic PTC. The low Ki-67 LI makes it unlikely that the proliferative capacity of the tumor cells contributed to the rapid progression. We believe that lymphatic flow was probably involved in this rapid tumor spread because tumor cells were mainly present within the dilated lymph vessels. This may explain the higher prevalence of nodal metastasis in DS-PTC than classic PTC.

In conclusion, we report two cases of DS-PTC newly developed during the follow-up of benign nodules and propose that MPEF may serve as a potential early sonographic indicator of DS-PTC development. We demonstrated that the progression of DS-PTC is extremely rapid compared with that of classic PTC. This rapid progression may be attributed to tumor cell dissemination via the lymphatic system.

Contributorsʼ Statement

Rie Goryo: Conceptualization, Data curation, Writing - original draft, Writing - review & editing. Mitsuyoshi Hirokawa: Conceptualization, Writing - original draft, Writing - review & editing. Ayana Suzuki: Writing - review & editing. Minoru Kihara: Writing - review & editing. Sayo Nishikawa: Writing - review & editing. Maki Oshita: Writing - review & editing. Hiroyuki Yamaoka: Writing - review & editing. Eijun Nishihara: Writing - review & editing. Makoto Fujishima: Writing - review & editing. Akira Miyauchi: Writing - review & editing. Takashi Akamizu: Supervision.

Conflict of Interest

The authors declare that they have no conflict of interest.

Publication History

Received: 26 February 2025

Accepted after revision: 05 November 2025

Article published online:
12 December 2025