Review

Brachial Plexopathy Due to Breast Cancer Metastasis: Report of a Case and Systematic Review of Literature

¹ Manoj Pandey, ² Mridula Shukla,

• ^{1.Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi ,India}
• ^{2.Consultant Pathologist and Lab Head, SRL Labs, Varanasi, India}

• Submitted : Wednesday, September 18,2018;
• Accepted:  Monday, October 29, 2018
• Published : Friday, November 14, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Abstract

Background:

Metastatic Brachial plexopathy is a rare and significant cause of morbidity in patients with breast cancer that is increasingly being diagnosed with use of FDG PET scanning.

Case Report:

A 55 years old woman presented with pain in the shoulder and  in arm, 5 years after undergoing bilateral mastectomy for infilterating ductal carcinoma. MRI and PET scan confirmed metastasis to brachial plexus and liver. Biopsy from the brachial plexus and immunohitochemistry confirmed it to be metastasis from breast cancer. Patient was treated with chemotherapy and is alive with disease.

Methods of review:

A literature search was carried out on Pubmed using a definite search strategy.

Results:

Using the Prisma guidelines and after the review of 23 abstracts, relevant studies were identified. Six studies were identified by back reference and cross references from these articles. Thus identified total 29 articles are reviewed.

Conclusions:

Metastatic involvement of brachial plexus is rare and is often part of disseminated disease elsewhere. Radiotherapy and systemic therapy is the treatment of choice. The prognosis is often poor and pain control is optimum with use of multimodal treatment.

Key words:

Breast cancer, metastasis,chemotherapy,PET scan,radiotherapy, prognosis,imaging

Background

Brachial plexopathy is a significant cause of morbidity in breast cancer patients. The patients often present with pain that is usually severe and radiating; and shoulder or arm disability. It is mostly related to radiation to the supraclevicular fossa, however there are other causes too that may contribute metastasis to the brachial plexus. Though rare, metastasis to the brachial plexus is increasingly being identified these days with the increasing use of PET scan for evaluation of these patients. Though difficult to image due to its proximity to blood vessels and lymphatics [1, 2], the development in modern imaging techniques especially, in magnetic resonance imaging and positron emission tomography has made it possible.

It is difficult to differentiate the plexopathy due to radiation from that due to metastasis however, absence of prior radiation and presence of lesions elsewhere along with careful review and interpretation of imaging data it is often possible to differentiate the two [1]. This is important as the management of the two is different. The prevalence of brachial plexopathy has been reported to be 0.4% from all causes [3] in a single centre study. Most of these are tumour of neural origin, extra nodal spread, while metastatic spread is common from breast and lung cancer. In the lung cancer the spread to the brachial plexus is supposed to be direct spread from apical lesions while in breast it is proposed to spread through perineural lymphatics from the axilla [4].

We report here a case of brachial plexus involvement by metastatic breast cancer in setting of disseminated metastasis and report the review of literature on metastatic brachial plexopathy.

Case Report

A 55 years old woman presented to surgical oncology out patient with complaints of severe pain in the shoulder with radiation to the arm and restriction of shoulder movements for past 3 months. She had seen her surgeon who had prescribed pain killers but there was no relief from pain except for few hours after taking the medicine. She had underwent bilateral modified radical mastectomy 5 years back for pT2N1 infilterating ductal carcinoma elsewhere and had received four cycles of adjuvant chemotherapy with Adriamycin and cyclophosphamide. No radiation was given at that time. The patient was not on regular follow-up after the completion of chemotherapy and her prior receptor status was not available.

On examination the vitals were stable, general examination revealed pallor. Examination of the neck revealed thickening of the brachial plexus, there were no supraclevicular nodes, examination of the chest wall and contralateral breast showed presence of nodularity on the chest wall under the MRM scar, right breast was normal however lymph nodes were present in the right axilla. Abdominal examination revealed hepatomegaly with liver span of 17 cm. No other abnormality was found.

With these findings patient was worked up. Haematological examination showed iron deficiency anaemia with haemoglobin of 7 gm/dL and microcytosis and anisocytosis, rest of the haematological parameters were normal. Biochemistry showed increase in the level of alkaline phosphatase and serum LDH levels, the renal function and rest of liver functions were normal. An ultrasonography of the abdomen revealed multiple liver lesions while chest X-ray was normal.

An Magnetic Resonance Imaging of the neck was carried out that revealed soft tissue density lesion in the region of the brachial plexus from C3 to C6 (Figures 1) and PET scan showed FDG avid uptake in brachial plexus, Liver, left chest wall, left axilla and right axilla (Figures 2,3). An image guided biopsy was obtained from liver and the brachial plexus that showed poorly differentiated (grade 3) carcinoma (Figures 4). Immunohistochemistry was performed that showed tumor to be positive for CK7, ER, PR and GATA while it was negative for CK20 and HER2 (Figures 5). With the diagnosis of infilterating mammary carcinoma (NOS) grade 3, rT1N1M1 pateint was started on palliative chemotherapy with docetaxel, epirubicin and carboplatin. Opioids were started for control of pain.

Figure 1: Magnetic resonance imaging picture showing the metastatic lesion at the C6/7 level. (A) T2 weighted image (B) T1 weighted image

Figure 2: FDG PET image (A) showing FDG avid lesion in Left brachial plexus and right axilla (B) Showing FDG avaid lesion in upper and lower brachial plexus (C) showing FDG Avid lesion in lower brachial plexus

Figure 3: FDG PET Image (A) Showing multiple metastatic lesions in the liver (B) Showing uptake over the left chest wall and left axilla

Figure 4: Photomicrograph showing pleomorphic cells in tubules with hyperchromatic nuclei and multinucleated cells seen (H&E x40)

Figure 5: Photomicrograph showing (A) CK 7 x10 (B) CK 20 x10 (C) GATA x10 (D) ER x10 (E) PR x10 (F) HER2x10

Patient received 8 cycles of chemotherapy showing partial response, however she complained of tingling and numbness in her lower limbs. Nerve conduction studies were performed that suggested peripheral neuropathy. Patient was shifted to second line single agent gemcitabine. After completion of three cycles of gemcitabine, patient complained of swelling in her arm with development of open wound on her right chest wall.

Examination showed a 3 x 3 cm ulcerated lesion on right chest wall with severe oedema of the right arm, the ultrasound of the abdomen showed increase in the size of liver lesions. As there was no response to gemcitabine she was shifted to third line Capecitabine and Vinorelbine combination therapy. Patient completed 6 cycles of chemotherapy amidst severe bone marrow toxicity that become apparent from fourth cycle onward and often delayed administration of chemotherapy, by the end of 6th cycle the toxicity was grade 3 and took almost 6 weeks to recover. Looking at the bone marrow toxicity and late recovery it was decided to put the patient on hormone therapy and she was started on Letrazole. She is alive with disease on letrazole after 3 months of starting the therapy and requires 80mg of morphene everyday to control her pain.

Review of Literature

A review of literature (Pubmed) was carried out using the following syntax on second September 2018 following the PRISMA guidelines.

(("brachial plexus"[MeSH Terms] OR ("brachial"[All Fields] AND "plexus"[All Fields]) OR "brachial plexus"[All Fields]) AND ("neoplasm metastasis"[MeSH Terms] OR ("neoplasm"[All Fields] AND "metastasis"[All Fields]) OR "neoplasm metastasis"[All Fields] OR "metastasis"[All Fields])) AND ("breast neoplasms"[MeSH Terms] OR ("breast"[All Fields] AND "neoplasms"[All Fields]) OR "breast neoplasms"[All Fields] OR ("breast"[All Fields] AND "cancer"[All Fields]) OR "breast cancer"[All Fields])

Result

This resulted in 65 articles, the title and abstract of these articles were screened and only 23 of these were found to be relevant to present case. Among the causes of exclusion the majority was as they were reporting on brachial plexopathy as a results of radiation therapy (23), complicationof surgery (6) complication of physiotherapy (1), Other lesions/mimics/other cancers (6) among others. Two cases of plexopathy of lower nerves were found and were also excluded (Figures 6). Six articles were identified through back references making a total of 29 articles reviewed.

Figure 6: Flow Diagram of literature review

Discussion

Brachial plexopathy is a rare condition that may occur due to numerous reasons most common among the patients with cancer are the radiation and metastasis. The plexopathy appears to be more common then reported, with increasing number of cases being reported in literature [2, 4-19]. The increasing detection can be contributed to the refinement in the techniques of CT and MR imaging [9, 13, 15, 18, 20, 21] and increasing use of PET scan in evaluation of breast cancer patient either upfront or in cases with suspected metastasis [1, 2, 10, 11, 22].

The presenting symptoms that suggest the involvement of brachial plexus is pain in the shoulder region and the arm with or without shoulder dysfunction. Conduction anomalies are also reported in some patients with sensory or motor loss [23]. The pain is often severe and intractable and often does not respond to NSAID’s. There are reports of treatment with opiates, radiation, pregablin and pulsed radiofrequency has been tried with limited results [24-27]. However, the best results appear to be with systemic chemotherapy or definite radiation [27, 28].

Behnke et al., [6] reported 4 cases of brachial plexus involvement treated with pericapsular amputation. At the time of their reporting 3 of their patients were alive with satisfactory pain relief while one died of progressive disease. Narakas AO [29] reported 5 pateints with metastatic plexopathy that were treated with surgical neurolysis out of 45 patients in their series. Our review failed to come across any other report of surgery being used to treatment of brachial plexus metastasis. It is apparent from the review that brachial plexus involvement is rarely isolated and most of these patients have other metastatic lesions and hence, use of systemic chemotherapy, tratsuzumab or hormone therapy appears to be more plausible options. Radiation can be used if the involvement is isolated.

Prognosis of the patients appears to be poor with most studies not reporting on long term outcome in these patients. The prognosis appears to be poor in patients with associated visceral metastasis compared to isolated metastasis. However, most of the evidence comes from isolated case reports and small retrospective reviews (Evidence level III/IV/V), no level I or II studies were identified in this review suggesting the need to accumulate all the cases reported in the literature and analysing the pooled results. Or in the current prospective studies that are ongoing in breast cancer, investigators should actively look for involvement of brachial plexus as well. It is however clear that with increasing use of FDG PET use for evaluation of breast cancer, more cases will be identified and reported and management of metastatic brachial plexopathy will improve.

Learning Points

1.Metastatic involvement of brachial plexus is rare

2.Breast and lung are the commonest primary tumor that metastatize to brachial plexus

3.In the breast cancer the spread appears to be through perineural lymphatics from axilla

4.In lung its mostly through direct involvement from apical tumors

5.Brachial plexopathy can also occur by extranodal spread from supraclevicular nodes

6.Management is by systemic treatment, while isolated metastasis can be treated by radiation

Authors Contribution

MP: designed the study, and edited the manuscript

MS: conducted the literature review and prepared the draft manuscript.

Consent for publication

The written informed consent was obtained from the patient for publication of this case report

Funding

None

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