Preoperational diagnosis and management of breast ductal carcinoma in situ arisi

lNTRODUCTlON

Fibroadenoma is the most common breast tumor found in young women[1,2]. Ductal carcinoma(DCIS) arising within a fibroadenoma is a specific pathological type of tumor that is rarely encountered in the clinic[3]. Its incidence ranges from 0.02% to 0.125%[4-6] and it is usually discovered by chance during pathological examination of fibroadenoma resected tissue. So far, approximately 100 cases for carcinoma arising within a fibroadenoma have been reported worldwide, including intraductal carcinoma, lobular carcinomaand invasive carcinoma, most of which lack preoperative follow-up data. Herein, we present 2 cases of breast DCIS arising within a fibroadenoma and discuss their clinical and imaging findings as well as treatment.

CASE PRESENTATlON

Chief complaints

A 49-year-old woman was diagnosed with a bilateral breast nodule in May 2018 (Figure 1A).The first ultrasound diagnosis showed a breast nodule of 8 mm × 5 mm × 7 mm in size, located in the left breast at the one o’clock direction. The tissue was hypoechoic, with an internal visible bright spot that was about 4 mm in length. Mammography suggested coarse granular calcified nodules behind the left areola and small nodules in the upper quadrant of the right breast (Figure 2A). No palpable masses were noted in either breast. It was recommended that she undergo regular ultrasound review (which was performed again in March 2019 and June 2021) and received no interventional treatment. In March 2019, ultrasound (Figure 1B) and mammography (Figure 2B) of these breast nodules showed no differences compared with the previous diagnosis. Yet, in June 2021 the ultrasound suggested an increase in the size (11 mm × 6 mm × 11 mm) of the breast nodule behind the left areola at the one o’clock direction. Moreover, coarse calcification plaques about 4 mm in length with Breast Imaging Reporting and Data System (BIRADS) grade IVA were found in the interior of the nodule.Mammography findings were similar to those observed previously. The patient had no remarkable physical complaints.

A 37-year-old woman was diagnosed with a left breast nodule in June 2021; yet, a specific size was not recorded. She was instructed to have regular ultrasound review, and no interventional treatment was given. The patient visited the outpatient clinic in July 2021 and underwent further ultrasound examination, which showed a nodule in the left breast at the five o’clock position. The nodule was approximately 15 mm × 9 mm × 11 mm in size with irregular morphology and uneven internal echogenicity but without calcification inside, and of BIRADS grade III. Mammography suggested no other abnormalities. During the history-taking, she revealed no remarkable physical complaints.

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History of present illness

Case 1 and case 2 have none present illness.

History of past illness

The patient’s previous medical history was unremarkable.

Case 1 and case 2 had no personal or family histories of breast malignancy.

Personal and family history

The patient was diagnosed with depression for over 9 years. Oral paroxetine was used to control symptoms.

Physical examination

Physical examination revealed the blood pressure to be 135/89 mmHg. No abnormalities were found in the cardiopulmonary and abdominal regions.The nipples were symmetrical,and the skin of both breasts was unremarkable, with no inversion of the nipple on either side and no significant nipple bleeding. No palpable masses were noted in either of the breasts, and no enlarged lymph nodes were palpable in the axilla and supraclavicular regions.

Blood pressure was 122/79 mmHg. Physical examination of the cardiopulmonary and abdominal regions revealed no abnormalities. The nipples were symmetrical, and the skin of both breasts was unremarkable, with no inversion of the nipple on either side and no significant nipple bleeding. A nodule of about 15 mm × 10 mm in size with moderate texture, poorly defined borders, and smooth surface was palpable in the outer lower quadrant of the left breast. No palpable mass was detected in the right breast. No enlarged lymph nodes were palpable in the axilla and supraclavicular regions.

Laboratory examinations

Sex hormone tests suggested estradiol ＜ 10 pg/mL, follicle-stimulating hormone 24.86 IU/L and luteinizing hormone 15.19 IU/L. The levels of carcinoembryonic antigen, cancer antigen (CA) 125,CA153 and CA199 were within normal limits.

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Carcinoembryonic antigen and CA199 levels were within normal limits.

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Imaging examinations

Breast and axillary lymph node ultrasound showed the nodule behind the left areola at the one o’clock position of the left breast was 11 mm × 6 mm × 11 mm in size with coarse calcified plaques about 4 mm in length diameter and BIRADS grade IVA (Figure 1C). The remaining bilateral breast had multiple nodules and BIRADS grade II-III. Mammography suggested a coarse granular calcified nodule posterior to the left areola, BIRADS category 2 (Figure 2C). Dynamic contrast-enhanced magnetic resonance imaging of the breast showed a left posterior papillary nodule, approximately 7 mm × 6 mm in size with a clear border and slightly lobulated appearance, a type II pattern on enhancement curve and lipohyalinosis hypointense foci on T1-weight imaging and T2-weighted imaging with possible posterior calcification and BIRADS 4a. There were multiple small nodules (BIRADS 3) throughout both breasts (Figure 3).

Zhong MC designed the report; Sun KW, Mo QP, Yang ZR and Chen Y collected the patient’s clinical data; Wu J and Zhong MC analyzed the data and wrote the paper.

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Pathological examination

It had been an excellent pregnancy, without medical restrictions21. Even so, he had not been able to make love to her for several months. He found himself wanting to protect her instead, to carry her up flights of stairs, to wrap her in blankets, to bring her cups of custard. I m not an invalid, she protested each time, laughing. I m not some fledgling（） you discovered on the lawn. Still, she was pleased by his attentions. Sometimes he woke and watched her as she slept: the flutter of her eyelids22, the slow even movement of her chest, her outflung hand, small enough that he could enclose it completely with his own.

The left breast nodule of the patient was completely resected and sent for pathological examination. Intraoperative hematoxylin and eosin-stained frozen sections results are shown in Figures 4 and 4B; paraffin sections after operation are shown in Figures 5A and 5B. DCIS on a background of fibroadenomas (all surrounded by a fibroadenomatous component) in a nested pattern was well demonstrated on both frozen and paraffin sections.

At the cross roads the two elder brothers debated if they should go the same way as the youngest, but when they saw how dreary and deserted25 it looked they made up their minds that it would be impossible to find what they sought in these wilds, and so they stuck to their former paths

FlNAL DlAGNOSlS

The 2 patients were diagnosed with breast DCIS arising within fibroadenoma. Immunohistochemical examination suggested estrogen receptor positivity.

TREATMENT

Both patients underwent breast-conserving surgery and sentinel lymph node biopsy. During the operations, the negative margin of the resected specimen and negative sentinel lymph nodes were confirmed with frozen sections.

OUTCOME AND FOLLOW-UP

Both patients recovered well after the operation. One patient received radiotherapy, while the other prepared to start radiotherapy (she consulted a radiotherapy physician and received an appointment for radiotherapy). The recommendation to begin endocrine therapy with tamoxifen was given. The followup is ongoing.

DlSCUSSlON

To the best of our knowledge, this is the first study that reported imaging results of DCIS arising within fibroadenoma, which might gradually develop into a prediagnostic follow-up tool that could facilitate decisions on when to perform surgical biopsies for breast nodules with an apparently benign tumor observed at follow-up. Moreover, these data demonstrate the importance of adequate sampling, which can increase the accuracy of early diagnosis. In addition, our results verified the value of frozen and paraffin sections for diagnosing this particular cancer type, thus allowing for a definite diagnosis to be made.

Breast DCIS arising within a fibroadenoma is a rare occurrence. To our knowledge, there are no previous reports on imaging data (including ultrasound and mammography) during the longer preoperative follow-up for DCIS developing in fibroadenoma. Herein, we reported 2 cases of breast DCIS arising within fibroadenoma:1 with a short medical history and 1 with more than 3 years of follow-up by ultrasound and mammography, subsequently confirmed by pathological examination.

20.Feathers of pure gold: Feathers are considered an element of air and are connected to contemplation and faith (Cirlot 103). Feathers are also a characteristic of lightness (Biedermann 137).Gold is considered to be superior. It can also be viewed as the essential element in the symbolism of the hidden or elusive29 treasure which is an illustration of fruits of the spirit and supreme30 illumination (Cirlot 120). Dummling gets the goose because he has a generous spirit. Gold is also the image of solar light and hence of the divine intelligence (Cirlot 119).The golden goose itself . . . leads to what folklorists call incremental31 repetition in which each new event builds on the previous one (Tater 283).Return to place in story.

Preoperative color Doppler sonography has a suggestive role in helping physicians make a correct diagnosis. In addition, longer preoperative follow-up imaging data allow us to review the developmental changes in this rare disease on imaging. Our data suggested that enlarged lesions with irregular margins, uneven texture, and concomitant calcifications could be important features for detecting this type of malignancy, which is consistent with previous studies[7,8].

Without adequate sampling and sectioning, a possibility of a missed diagnosis of intraductal carcinoma or even invasive carcinoma of such a focal location within a fibroadenoma increase. In addition, it is possible that the dysplastic ductal epithelium, or even carcinoma, could not be identified because frozen sections were only selected[9], although the ability of frozen sections for the diagnosis of this particular cancer type is adequate. In addition, some experts argue that invasive carcinomas arising in fibroadenomas could have similar prognostic features as intraductal carcinomas.

These 2 cases of breast DCIS arising within a fibroadenoma also clearly suggest that fibroadenomas should not be ignored and warrant close follow-up. Based on the course of the follow-up and diagnosis in the above cases and referring to the previous literature, a significantly enlarged mammary nodule with irregular morphology or uneven internal echogenicity under ultrasound may indicate the need for biopsy or surgical intervention[10].

In general, the clinical and macroscopic features of DCIS arising within a fibroadenoma rarely differed from those of common DCIS[11]. Therefore, the treatment of this particular entity may be similar to the treatment of common DCIS. Based on the prognosis of carcinomawithin fibroadenomas, some scholars recommend breast-conserving surgery as the preferred treatment modality[11]. Only a small amount of adjacent breast tissue is usually included around the biopsy specimen. Therefore, biopsy is inadequate to assess adjacent mammary ducts. Re-excision is recommended. Mastectomy may also be performed if the patient wishes to approach “near-certain cure”[11]. In current National Comprehensive Cancer Network guidelines, patients suffering from DCIS treated with lumpectomy would be recommended to receive radiotherapy first, with the exception of those with lower recurrence risk factors. Whole breast radiation therapy with or without boost to tumor bed is the preferred method of radiotherapy (category I). The patients with DCIS without the high recurrence risk factors, such as age ＜ 50 years, larger size, higher grade, palpable mass and close or involved margins, may be treated by excision alone. This propensity to excision alone would be stronger if they were estrogen receptor-positive because there are also endocrine therapies that can be used for treatment.

Despite the favorable prognosis, it remains unknown whether radiotherapy can be exempted after breast-conserving surgery in DCIS arising within a fibroadenoma. An analysis assessing 20-year mortality outcomes in patients with DCIS demonstrated no survival benefit to radiation, although it did reduce local recurrence risks significantly[12,13]. Relevant clinical studies could be designed but there are no recommendations in the current guidelines. In clinical practice, we may be more cautious in decisions about the treatment adopted for DCIS arising within a fibroadenoma. Referring to the recent guideline recommendations for common DCIS, age ＜ 50 years was one of the recurrence risk factors.Therefore, the 2 patients received or will receive radiotherapy for treatment.

As recommended by National Comprehensive Cancer Network guidelines, DCIS patients are recommended routine genetics consultation. In addition to tumor type, age of cancer onset was also found to be a statistically significant indicator for germline referral[14]. The 2 cases involved in this report were both young patients, making genetic testing more valuable (it may find BRCA1/2 mutations,.). Regrettably, neither patient accepted this recommendation.

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The patient’s left breast nodule was excised by a vacuum-assisted biopsy system and then sent for pathological examination. Intraoperative hematoxylin and eosin-stained frozen section results are shown in Figure 4C and 4D and postoperative paraffin section findings in Figures 5C and 5D. The frozen section showed no dysplasia of the ductal epithelium within the fibroadenoma, either at low or medium magnification. In postoperative paraffin section analysis, a focal intraductal carcinoma component within a fibroadenoma was found.

Both of the patients showed estrogen receptor positivity. They were administered endocrine therapy with tamoxifen accordingly. As recommended by the recent National Comprehensive Cancer Network guidelines, endocrine therapy is considered the risk-reduction treatment of the ipsilateral breast after surgery in patients with DCIS undergoing breast-conserving surgery, especially in patients with estrogen receptor-positive DCIS. Patients are treated with tamoxifen during the premenopausal period and with tamoxifen or an aromatase inhibitor during the postmenopausal period.

CONCLUSlON

Breast DCIS arising within a fibroadenoma is rare. More sections are needed to reduce the missed rate.Complete follow-up data with preoperative imaging can help us make decisions during patient followup. Taken together, it remains uncertain whether a more conservative approach can be taken in the adjuvant setting for breast DCIS arising within a fibroadenoma.

The authors express special thanks to Dr Ke-Wang Sun who guided this work.

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Breast and axillary lymph node ultrasound showed the nodule located at the five o’clock direction in the left breast. The nodule was approximately 15 mm × 9 mm × 11 mm in size with irregular morphology, uneven internal echogenicity, without calcification inside, and BIRADS grade III(Figure 1D). Mammography suggested mammary hyperplasia and BIRADS category 3 (Figure 2D).Dynamic contrast-enhanced magnetic resonance examination of the mammary gland was not performed.

The patients consented to submission of their anonymized cases and accompanying images.

The authors declare having no conflicts of interest.

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The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

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China

Jun Wu 0000-0002-6808-3207; Ke-Wang Sun 0000-0002-4839-477X; Qiu-Ping Mo 0000-0001-5667-5726;Ze-Ran Yang 0000-0003-0615-0256; Yuan Chen 0000-0002-9476-8816; Miao-Chun Zhong 0000-0003-2949-4967.

Wang JJ

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Wang JJ