Paraneoplastic cerebellar degeneration as a manifestation of metastatic recurrent carcinoma breast: rare scenario

Abstract

Carcinoma breast presenting with paraneoplastic cerebellar degeneration is a rare scenario. We report a case of a 52-year-old woman, which is a follow-up case of completely treated carcinoma breast presenting with paraneoplastic cerebellar degeneration which, on investigation, revealed metastatic disease with recurrence at previous scar site and metastasis to contralateral axilla. The patient was given pulse methyl prednisolone therapy and underwent wide local excision of nodule and right axillary lymph node dissection with 14 cycles of trastuzumab and paclitaxel as adjuvant therapy. However, there was no detectable change in neurological symptoms at 6-month follow-up postoperatively. This case report highlights the need for clinicians to be aware of all possible presentations of carcinoma breast and its recurrence, including rare manifestations as in this case.

Background

Paraneoplastic syndromes are defined as clinical disorders associated with malignant diseases that are not directly related to the physical effects of the primary or metastatic tumour.¹ Cancers of the lung, breast, genitourinary system and lymphomas are known to have remote effects on the neurological system, although rarely.² Paraneoplastic cerebellar degeneration (PCD) is the second most common paraneoplastic syndrome following paraneoplastic neuropathies.³ PCD as presenting manifestations of occult carcinoma breast have been reported in literature. PCD may present occasionally several years after the treatment of primary breast cancer with the development of metastatic disease.⁴ We report the case of a woman, which is a follow-up case of completely treated carcinoma breast presenting with PCD which, on investigation, revealed metastatic disease. Very few cases of PCD presenting as metastatic breast carcinoma have been reported.

Case presentation

A 52-year-old woman came with complaints of lump in her left breast. Clinical examination was consistent with malignant breast lump. Core biopsy revealed infiltrating ductal carcinoma grade 3, hormone receptors (Estrogen receptor/Progesterone receptor (ER/PR)) negative and Her2Neu 3+. She received three cycles of Cyclophosphamide Adriamycin Fluorouracil (CAF) neoadjuvent chemotherapy followed by Modified Radical Mastectomy (MRM). Postoperatively, she received locoregional radiotherapy and four more cycles of chemotherapy and transtuzumab. She remained asymptomatic for 2 years after which she started having subtle speech abnormalities—drawing out individual syllables associated with slight change of gait due to loss of coordination. The symptoms were initially mild, progressed rapidly over 20 days and the patient eventually became wheelchair users. On physical examination, her vitals were stable, neurological examination revealed scanning speech, reduced tone of all four limbs and gross dysmetria of all four limbs with axial instability. Finger nose test and heel shin test were positive with gross intentional tremor and dysdiadochokinesia. Other significant findings were presence of a nodule over the previous mastectomy scar and palpable nodes in the contralateral axilla (figure 1). Routine laboratory investigations were within normal limits, and anti-Yo antibody was positive. A whole body Positron Emission Tomography (PET) scan revealed an area of increased metabolic activity in the left breast nodule and right axillary and internal mammary nodes (figure 2). MRI brain did not show cerebellar atrophy or evidence of metastasis. Core biopsy from both chest nodule and axilla yielded Invasive ductal carcinoma (IDC) grade 3, ER/PR− and Her2Neu3+. Diagnosis of PCD was made, and pulse methyl prednisolone was administered for 5 days. Intravenous Immunoglobulin (IVIG) therapy was advised, but due to financial constraints, patient could not afford it. The patient underwent further surgery in the form of wide local excision of nodule and right axillary lymph node dissection. Adjuvant therapy in the form of 14 cycles of transtuzumab with paclitaxel was given. Postoperative recovery was uneventful.

Figure 1.

Showing local tumour recurrence.

Figure 2.

PET showing increased uptake in local recurrence site and contralateral axilla.

Outcome and follow-up

There was no detectable change in neurological symptoms at 6 months postoperatively though there was no rerecurrence of tumour.

Discussion

Pathophysiology of Paraneoplastic cerebellar degeneration

Tumour cells also express normally expressed proteins in neurons (onconeuroantigens). Cross-presentation of these onconeuroantigens by dendritic cells (from the phagocytosed tumour cell to both CD4+ and CD8+ T cells) lead to PCD. Her2Neu overexpression is seen in about 15%–25% of breast tumours and is associated with a more aggressive tumour behaviour and poor prognosis. Few studies also suggest that breast tumours with anti-Yo-associated PCD overexpress Her2Neu.⁵ The possible explanation to this relationship between HER2-positive breast cancer and anti-Yo-associated PCD might be that HER2-positive breast cancers are prone for early regional lymph nodes invasion, and this behaviour would favour the development of anti-Yo antibodies if the cancer cells expressed cdr2. Another possible explanation for the association is that cdr2 expression is restricted to HER2-positive breast tumours.⁶ Clinical signs of neuronal degeneration occur due to immune recognition of neurons that normally express the target PND antigens causing neuronal injury. It is because of similarity of Purkinje neuronal protein (Cdr2; normally expressed in cerebellum) and the tumour antigen (expressed in breast and ovarian tumours for anti-Yo antibody).⁷ There are many other antibodies associated with various malignancies causing PCD (table 1).

Table 1.

Common antibodies associated with malignancies causing PCD

Antibody	Malignancy
Anti-Yo	Ovary and breast
Anti-Hu	SCLC
Anti-Ri	Breast and SCLC
Anti-Tr	Hodgkin’s lymphoma
Anti-CV2	SCLC
Anti-Ma protein	Testicular

PCD, paraneoplastic cerebellar degeneration; SCLC, small cell lung cancer.

In about 60% of cases, patients present with PCD months or years before the diagnosis of underlying malignancy is established.⁸ On rare occasion, it occurs in patients with a known cancer or heralds the onset of a recurrence.⁴ PCD is characterised classically by subacute development of rapidly progressive symptoms of cerebellar dysfunction, which eventually stabilise but leave the patient incapacitated with a global cerebellar syndrome. According to some studies, the patients of carcinoma breast with PCD have median survival of about 100 months.⁹ In this case, our patient received different modalities of therapy like chemotherapy, steroids and surgery, but her neurological symptoms did not improve rather progressed. Treatment is mainly aimed at the supportive rehabilitation of the cerebellar abnormality along with the eradication of the malignancy. It seems that the prognosis and survival of negative anti-Yo antibody PCD patients is same as with the patients with isolated breast cancer. However, anti-Yo antibody positive patients have more aggressive cerebellar disease course with majority of patients eventually requiring an assistive device for ambulation and have significantly poorer survival.¹⁰

Learning points.

• Carcinoma breast can present with rare symptoms though it is a common malignancy.

• Paraneoplastic cerebellar degeneration may be a differential in a case of carcinoma breast presenting with symptoms of incoordination.

• Other causes of cerebellar degeneration should be ruled out before implicating paraneoplastic degeneration as the cause, in a case of carcinoma breast.