Papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer:A case report

lNTRODUCTlON

Thyroid cancer and breast cancer (BC) are very common in women[1] and both can involve cervical lymph node metastasis (CLNM). The most common type of thyroid cancer is papillary carcinoma, and papillary thyroid microcarcinoma (PTMC) accounts for the majority of cases. When it comes to multiple primary cancers, such as PTMC and BC, the origin of CLNM needs to be distinguished. CLNM in PTMC is usually related to a relatively poor prognosis, especially for lateral CLNM. The recognized pattern of CLNM of PTMC involves a stepwise route. The first site involved is the central compartment, followed by the ipsilateral lateral lymph node (LN) compartment. The contralateral and the mediastinal LN compartments then follow suit[2,3]. Contralateral LN skip metastasis is very rare. CLNM in BC is usually indicative of a terminal stage.

Here, we report a rare case of PTMC with contralateral lymphatic skip metastasis and BC with supraclavicular lymphatic metastasis.

CASE PRESENTATlON

Chief complaints

A 53-year-old woman presented to the hospital with a neck mass in her left lateral cervical region.

History of present illness

The patient’s symptom started 2 mo prior and she had not received any treatment in that period.

For a time it had seemed Rebekah s chemotherapy was working. Then doctors discovered another malignant11（） lump. Two months later, a chest X-ray revealed the cancer had spread to her lungs. It was terminal. Help me to help her through this, I prayed.

History of past illness

The patient had a free medical history.

Then it may be that I shall succeed, and if I return with my purpose fulfilled I will marry you according to the law, and take you to my own country, and we will spend the rest of our lives together in pleasure and good companionship

Personal and family history

Although most PTMC diagnoses have an excellent prognosis due to its indolent nature, some tend to be aggressive and are related to a poor prognosis[10]. The PTMC in our patient was T1aN1bM0 (IVa)stage according to the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system[11]. Therefore, radical therapy was recommended. Because PTMC usually has a high incidence of multifocality and the presence of contralateral abnormal LNs[10], we could not exclude the existence of occult PTMC in the left lobe preoperatively. The patient underwent total thyroidectomy instead of lobectomy for complete resection of malignant tumors that allowed subsequent radiotherapy. Furthermore, prophylactic central compartment bilateral neck dissection was conducted for the presence of clinically involved lateral LNs (cN1b) as recommended by the 2015 American Thyroid Association guidelines[11]. However, a longer follow-up time was needed to learn the long-term prognosis of this patient. The BC was in a terminal stage as soon as it was discovered. In fact, it may have been discovered earlier if a more detailed examination had been performed at her first visit. The level V metastatic LNs discovered in the first surgery were not evaluated by further immunohistochemistry and were assumed to also be contralateral skip metastatic LNs. However, we cannot exclude that it may have originated from BC.

Physical examination

34. Sheepshanks Cruickshanks, Spindleshanks?: These names are even more nonsensical than the ones provided the day before, primarily used for their rhyming qualities.

In 1945, there was a young boy of 14 in a concentration camp（）. He was tall, thin but had a bright smile. Every day, a young girl came by on the other side of the fence. She noticed the boy and asked him if he spoke1 Polish, and he said yes. She said he d looked hungry, and he said he was. She then reached in her pocket and gave him her apple. He thanked her and she went on her way. The next day, she came by again, bringing with her another apple which she gave him. Each day, she walked by the outside of the fence, hoping to see him, and when she did, she happily handed him an apple in exchange for（） conversation.

Laboratory examinations

That is such a cat thing to do, said Thomas Graves, a feline4 expert and chief of small animal medicine at the University of Illinois College of Veterinary Medicine.

Imaging examinations

Ultrasound (US) examination showed a 7.8 mm × 7.4 mm heterogeneous hypoechoic nodule in the right lobe of the thyroid gland (Thyroid Imaging Reporting and Data System category 4B). In addition,several abnormal LNs were detected in level V; the biggest one being approximately 14.0 mm × 7.0 mm in size (Figure 1).

Further diagnostic follow-up

US-guided fine needle aspiration biopsy was taken for further evaluation. It indicated that the nodule in the right lobe was PTMC, and the LN was malignant. We preliminarily concluded that this patient suffered from PTMC accompanied by CLNM.

The patient underwent total thyroidectomy and radical cervical neck dissection (bilateral central LN and left lateral LN). Postoperative pathology found isolated PTMC in the right lobe, which was also supported by the findings of immunohistochemical analysis [CD56 (partly positive), HBME-1(negative), galectin-3 (positive), CK19 (partly positive), TPO (negative), Ki67 index (1%)]. Surprisingly,the bilateral central cervical LNs (= 16) were all disease-free. Metastasis was found, involving one LN in the left level V and one LN in levels III and IV (Figure 2). Immunohistochemical analysis of the metastatic LN in left levels III and IV were positive for galectin-3 and CK19, and were negative for CD56, HBME-1 and TPO. The Ki-67 index of 1% indicted that the left lateral CLNM in levels III and IV had originated from the thyroid.

No local relapse was found by US at the next 3-mo follow-up. The patient intended to receive iodine-131 therapy; however, she was admitted to our hospital for a large mass in her left breast 1 mo later.Mammography showed a mass of approximately 3.7 cm ′ 2.6 cm in the left breast, which was highly suspicious of malignancy (Breast Imaging Reporting and Data System 5). US also showed several abnormally enlarged LNs in the left axillary, supraclavicular and level V. US-guided core needle biopsy was taken for the breast mass, which revealed infiltrative carcinoma originating from the breast by pathology and immunohistochemical analysis. US-guided fine needle aspiration biopsy was taken for the suspicious LNs, including the left axillary, supraclavicular and level V, which were all determined to be malignant. It was unknown whether the CLNM in the supraclavicular and level V area originated from the thyroid or breast. The patient underwent another thyroid US. Several hypoechogenic structures could be detected in levels IV and V with irregular shape, obscure boundary and unclear lymphatic hilus. The findings were highly suspicious of metastatic LNs, and we first considered origination from the breast (Figure 3). No distant metastasis was found upon further examination.

FlNAL DlAGNOSlS

PTMC with contralateral lymphatic skip metastasis and BC with supraclavicular lymphatic metastasis.

TREATMENT

Given that the BC was in an advanced stage (cT2N3M0), the patient underwent four cycles of neoadjuvant chemotherapy with epirubicin (145 mg/m) and cyclophosphamide (900 mg/m), followed by four cycles with docetaxel (150 mg/m). Clinical responses in the breast and LNs were assessed by US after the neoadjuvant chemotherapy treatment, and she was determined to have achieved partial remission. Then, she underwent a left modified radical mastectomy. Postoperative pathology of the breast revealed invasive ductal carcinoma accompanied by a few invasive micropapillary carcinomas and intermediate grade ductal carcinoma. In addition, three of the seventeen LNs were metastatic. The immunohistochemistry profile of the specimen was as follows:estrogen receptor (+,strong, 95%); progesterone receptor (+, strong, 80%); human epidermal growth factor receptor-2 (1+);Ki-67 (15%); androgen receptor (60%); E-cadherin (+); GATA3 (+); mucin (+); cytokeratin 5/6 (-);epidermal growth factor receptor (-); D2-40 (-); and P63 (-).

OUTCOME AND FOLLOW-UP

We have reported, here, the first case of a rare contralateral LN skip metastasis of PTMC accompanied by BC. Bruno[4] reported a similar case of contralateral LN skip metastasis in Germany. However,those authors identified the unusual pathway of CLNM, mainlythe detection of high thyroglobulin levels in the wash-out liquid of fine-needly aspiration biopsy. In our case, it was mainly based on the postoperative immunohistochemical findings.

DlSCUSSlON

The patient is currently receiving postoperative radiotherapy for control of the metastatic lesions. At the 6-mo follow-up, US assessment revealed no local recurrence.

We raised two hypotheses for this kind of phenomenon. First, there may be unknown cervical LN drainage pathways. Second, there may be occult PTMC in the left lobe. A previous study reported cases of occult PTMC without detection of the primary tumor[5,6]. In one, Yamashita[5] hypothesized that the primary tumor was PTMC of less than 5 mm, as it was difficult to prepare slices of pathological specimens thinner than 5 mm.

Our patient, described herein, had developed cancers of PTMC and BC. However, the US-fine needle aspiration biopsy of LNs in the supraclavicular and level V areas failed to show the origin of her metastasis, which was crucial information. We hypothesized that they had originated from the BC instead of PTMC, for the following reasons. First, the most common sites of lateral CLNM in PTMC are levels II to IV. CLNM in level V is comparatively rare[7,8]. Second, the metastatic LNs of PTMC may show specific features, such as microcalcifications and cystic appearance, on US[9], which was not observed in our patient. Third, the size of the metastatic cervical LNs obviously decreased after neoadjuvant chemotherapy for BC.

The patient denied any relevant personal family history, particularly for thyroid issues.

CONCLUSlON

Here, we describe a case of PTMC with contralateral lymphatic skip metastasis and BC with supraclavicular lymphatic metastasis, which has rarely been reported in the literature. Both thyroid cancer and BC may involve CLNM. The characteristics of US, more detailed immunohistochemistry examination findings, and knowledge of the sites of CLNM may help to distinguish the origin of CLNM. In addition,when it comes to uncommon CLNM of the primary cancer, a more detailed examination such as by head-neck computed tomography, chest computed tomography and physical examination is strongly recommended.

We would like to thank Liu-Shu Jiang and Jun Liu for assisting with data collection.

Thyroid function and autoimmune antibody were all in normal ranges, except for the anti-thyroid peroxidase (TPO) antibody (787.40 IU/mL; normal range:0-9 IU/mL). Routine blood indexes were all within normal range. Tests for serum tumor markers, including carcinoembryonic antigen, alphafetoprotein, carbohydrate antigen 19-9, CA242, cytokeratin 19 fragment and squamous cell carcinoma antigen, were all negative.

A nodule of approximately 0.8 cm in diameter was found in the right lobe of the thyroid gland. It was not tender and easily moved upward and downward when she swallowed. A firm mass of roughly 1.0 cm was palpated in the left lateral cervical region.

Ding M reviewed the literature and contributed to data analysis and manuscript drafting; Kong YH and Xie RL were responsible for data collection; Fei J and Gu JH were responsible for the revision of the manuscript, considering and providing important intellectual content; All authors issued final approval for the version to be submitted.

The Project of Shanghai Municipal Health Commission, No. 20214Y0223.

Sonali picked up some dirt in her hands, folded her hands in prayer and began singing a beautiful hymn14 she learned in India the previous winter. Everyone stopped to listen to her. Then she held the dirt to her heart and threw it toward the plane.

Informed written consent (surgical operation) was obtained from the patient.

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

The authors declare that they have no conflicts of interest.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See:https://creativecommons.org/Licenses/by-nc/4.0/

China

Min Ding 0000-0001-5444-9397; Ya-Hui Kong 0000-0002-6708-6297; Jian-Hua Gu 0000-0002-3501-7692;Rong-Li Xie 0000-0002-5266-383X; Jian Fei 0000-0001-7159-8562.

Shanghai Association of Chinese Integrative Medicine Thyroid Professional Committee.

Gong ZM

52.A gold carding-comb: Again, the heroine receives a golden example of a domestic item, this time a carding-comb. A carding-comb is a toothed instrument used for separating and cleansing110 wool, flax, hair, etc. (Webster s 1990). It is used in clothing production, a traditionally feminine domestic chore.Return to place in story.

A

10. King Thrushbeard: A man s beard is linked with his dignity (Biedermann 34), so the insulting name is a direct attack on Thrushbeard s pride. Marie-Louise Franz associates Thrushbeard with Woton (Odin) (172), the Norse god of wisdom and as an aspect of the animus (170). Von Franz writes of the animus ridden woman, the worst condition comes about when a woman has a powerful animus and does not even live with it, then she is being straight jacketed by animus opinions, and while she may avoid any work that seems in least masculine, she is much less feminine (174). By refusing all her suitors, even the most worthy ones, the princess is not fulfilling what was seen as the proper role of a woman (to marry and produce children).

And when they stood before the throne on which the princess sat, they could do nothing but repeat the last words she had said; and she had no particular wish to hear her own words over again

Gong ZM