Key findings:

The abstract highlights a rare case of breast cancer metastasis to the scalp, signaling disease progression, despite radical treatment. Breast cancer commonly metastasizes to bones, lungs, liver, and brain, but scalp metastasis is uncommon. This case underscores the need for vigilance in monitoring patients for distant metastases even after successful radical treatment.

What is known and what is new?

Breast cancer commonly metastasizes to bones, lungs, liver, and brain, with scalp involvement being rare. This abstract presents a novel case of breast cancer with scalp metastasis after ten years of radical treatment. It underscores the importance of vigilance for distant metastases, even years after successful primary treatment.

What is the implication, and what should change now?

The occurrence of scalp metastasis in breast cancer, though rare, signifies disease progression and highlights the need for vigilant monitoring even post-treatment. Clinicians should consider regular follow-ups and comprehensive assessments to detect such late metastases, facilitating timely intervention and optimizing patient outcomes.

Breast cancer is the most common malignancy in females and second major cause of death among females. This year, an estimated 284,200 people (281,550 women and 2,650 men) in the United States will be diagnosed with invasive breast cancer. Breast cancer is the second leading cause of death in women, of which the majority of deaths are caused by metastatic breast cancer. The five year survival rate for women with metastatic breast cancer is 28% [1]. The most common sites for metastasis in breast cancer are bone, lung, liver and brain. Scalp metastasis is exceedingly rare and is a sign of disease progression and poor prognosis [2]. Here we are reporting a case of primary breast cancer in a 62 year old female who after ten years of treatment with surgery, local radiation therapy and chemotherapy developed scalp metastasis.

A 62 year old female patient who was diagnosed with a case of carcinoma right breast in 2010 presented at our department four months back with a nodule on the scalp region. She was a biopsy proven Stage IIc Ductal cell carcinoma positive for estrogen, progesterone receptors and negative for Her-2-neu. She received four cycles of neo adjuvant chemotherapy with paclitaxel, adriamycin and cyclophosphamide (TAC) followed by right modified radical mastectomy and then four cycles of adjuvant chemotherapy with TAC. She then received hypofractionated radiation therapy to the chest wall, axilla and supraclavicular region at a dose of 40 Gy in 15 fractions. She was then started on hormonal treatment with tablet Letrozole for 7 years. She has been on regular follow up since then. Four months back she presented with a hard painless mass on the scalp in the frontal region. It was about 3.5x3 cm, a hard nodule fixed to overlying skin. It was not fixed to the underlying bone and was freely mobile. There was partial alopecia at the site of the nodule. A trucut biopsy was done and histopathology was suggestive of skin and fibroadipose tissue infiltrated by tumor in small nests. The cells show moderate nuclear pleomorphism, hyperchromatic nuclei and moderate cytoplasm suggestive of metastatic carcinoma. For further work up an immunohistochemistry was done which was suggestive of estrogen receptor 90% positive and GATA-3 was immunoreactive, 4+ score. A final diagnosis of Metastatic Adenocarcinoma from breast primary was made. A further work up was done and a PET scan was done suggestive of advanced metastatic disease with metastasis to sacral, iliac bones, multiple mediastinal and left supraclavicular lymphadenopathy and multiple liver metastasis. There was no local recurrence. She was then referred to the medical oncology department for palliative chemotherapy. So far she has received two cycles of chemotherapy with minimal symptomatic improvement.
 

Scalp metastasis in breast cancer is extremely rare. Scalp tumors account for 2% of all skin tumors and may originate from the epithelium, pilosebaceous unit, eccrine, and apocrine or present as metastases [2]. Chuang et al., studied patients with scalp lesions and found 12.8% to be malignant lesions. He further concluded lung cancer to be the most common primary followed by colon, liver and breast [7.84%] [3].

Breast cancer spreads via lymphatic and hematogenous routes. It can be localized, regional or distant spread. Localized spread is to regional lymph nodes and distant spread is to sites like bone, liver, lung, brain. Scalp metastasis is extremely rare and is a sign of disease progression [2].

Cutaneous metastasis in breast comprise about 0.7 to 9% of all metastasis. They usually arise from the skin over breast lesion or a site that is proximal to it. There are different morphological types like solitary to multiple erythematous infiltrating nodules or masses, carcinoma erysipeloides, carcinoma en cuirasse, carcinoma telangiectaticum, alopecia neoplastica, and zosteriform pattern [4].

In our patient there was a previous history of breast cancer about ten years back for which she was radically treated with surgery followed by chemotherapy and radiation therapy to the chest wall. She has been on follow up since then. Four months back she presented with lesion on the scalp region in the frontal region which on biopsy was metastatic deposit and on immunohistochemistry was diagnosed as secondary from breast cancer. She had no sign of metastasis before that and as stated above when she was further worked up there were metastases to iliac, sacral bone, regional lymph nodes and diffuse liver metastasis. These findings are consistent with the above statement that scalp metastasis represents an advanced metastatic disease.

One challenge in this scenario is to differentiate scalp lesion to be primary skin adnexal or from breast primary. These both are adenocarcinoma and also there is a lack of specific markers to differentiate them. A panel of immunohistochemistry is required but it is also not very sensitive. The markers like mammoglobin, gross cystic disease fluid protein (GCDFP) and estrogen receptor are positive in both breast cancer and skin adenocarcinomas [5]. Majority of breast cancers are CK7 positive and CK20 negative, however CK7 negative breast cancer are also present [6]. GATA-3 has become popular in the breast cancer literature as a sensitive marker for breast carcinoma; however, it lacks specificity and should be used in conjunction with other markers [7]. P63 is another important marker as breast cancer is negative or focally positive for this, while skin malignancies are strongly positive for this marker [8]. Thus a panel of markers should be done. 

In our patient, the estrogen receptor was 90% positive, and GATA-3 was immunoreactive, 4+ in neoplastic cells and thus a diagnosis of breast primary with scalp metastasis was made. 

She was then referred to the medical oncology department and started on palliative chemotherapy. She has completed two cycles of chemotherapy with minimal symptomatic improvement.

Scalp metastases in breast cancer are extremely rare and indicate a very advanced, poor prognostic disease. The first challenge is to differentiate it from skin adnexal adenocarcinoma owing to fewer specific markers for differentiation. This is so rare that there are a limited number of studies for the diagnosis and treatment. Thus, more and more studies are warranted in future for effective diagnosis and treatment.  

Funding: No funding sources.

Conflict of interest: None declared.

Ethical approval: The study was approved by the Institutional Ethics Committee of Himachal Hospital of Psychiatry illnesses and deaddiction center.

1. Breast Cancer - Metastatic: Statistics: American Cancer Society's (ACS) publication, Cancer Facts & Figures zzzzzzz (2021)  .
2. Prabhu, Smitha, et al. "Cutaneous metastases from carcinoma breast: The common and the rare." Indian Journal of Dermatology, Venereology and Leprology 75 (2009): 499. https://ijdvl.com/cutaneous-metastases-from-carcinoma-breast-the-common-and-the-rare/ 
3. Chiu, Cheng-Sheng, et al. "Malignant cutaneous tumors of the scalp: a study of demographic characteristics and histologic distributions of 398 Taiwanese patients." Journal of the American Academy of Dermatology 56.3 (2007): 448-452. https://doi.org/10.1016/j.jaad.2006.08.060 
4. Rolz-Cruz, Gabriela, and Caroline C. Kim. "Tumor invasion of the skin." Dermatologic clinics 26.1 (2008): 89-102. https://doi.org/10.1016/j.det.2007.08.004 
5. Bhargava, Rohit, et al. "EGFR gene amplification in breast cancer: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations." Modern pathology 18.8 (2005): 1027-1033. https://doi.org/10.1038/modpathol.3800438 
6. Hashimoto, Kenji, et al. "Immunohistochemical profile for unknown primary adenocarcinoma." PLoS One 7.1 (2012): e31181. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031181 
7. Miettinen, Markku, et al. "GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors." The American journal of surgical pathology 38.1 (2014): 13-22. DOI: 10.1097/PAS.0b013e3182a0218f
8. Rollins-Raval, Marian, et al. "An immunohistochemical panel to differentiate metastatic breast carcinoma to skin from primary sweat gland carcinomas with a review of the literature." Archives of pathology & laboratory medicine 135.8 (2011): 975-983. https://doi.org/10.5858/2009-0445-OAR2