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- Hindawi Publishing Corporation
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- Copyright © 2019 Anita Pandey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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- 10.1155/2019/4307281
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Abstract
Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 4307281, 6 pages https://doi.org/10.1155/2019/4307281 Case Report Case Reports on Metaplastic Squamous Cell Carcinoma of the Breast and Treatment Dilemma 1,2,3 1,2,3 1,2,3 1,2,3 Anita Pandey , Kishor Joshi, Harry Moussouris, and Gardith Joseph Department of Hematology and Oncology, Brookdale University Hospital Medical Center, USA Department of Internal Medicine, Brookdale University Hospital Medical Center, USA Department of Pathology, Brookdale University Hospital Medical Center, USA Correspondence should be addressed to Anita Pandey; anita_pande@hotmail.com Received 2 May 2019; Accepted 5 September 2019; Published 18 September 2019 Academic Editor: Katsuhiro Tanaka Copyright © 2019 Anita Pandey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Metaplastic squamous cell carcinoma of the breast is a very rare form of breast cancer that consists of both glandular and nonglandular components mixed with epithelial and mesenchymal tissues. Worldwide, the incidence of this tumor is between 0.1 and 2%. Because of the rarity of this tumor and heterogeneous behavior of the tumor cells, it is difficult to establish the standard therapeutic approach. We report 2 cases of metaplastic squamous cell carcinoma of the breast in young patients with different responses to treatment strategies. The first case is a premenopausal female with metaplastic squamous cell carcinoma treated with surgery, chemotherapy, and radiotherapy, and the second case is perimenopausal metaplastic squamous cell carcinoma with sarcomatoid subtype and osteoid matrix production which progressed on chemotherapy and was treated with surgery and radiation. 1. Introduction grade adenosquamous carcinoma, squamous cell carcinoma, spindle cell carcinoma, and fibromatous-like metaplastic carcinoma; second, metaplastic carcinoma with mesenchy- Squamous cell carcinomas (SCC) are common in the skin and respiratory and upper GI tracts lined by squamous cells. mal differentiation that includes chondroid differentiation, Metaplastic breast carcinoma is a rare malignancy [1, 2]. The osseous differentiation, and other types; and third, the Surveillance, Epidemiology, and End Results (SEER) data- mixed type. When the squamous cell component (SCC) pre- base of the National Cancer Institute (NCI), from 2011 to dominates by more than 90%, they are pure squamous cell carcinoma and tend to be more aggressive and treatment 2015, shows a total of 168 cases of epidermoid carcinoma which accounted for 0.1% of total invasive breast carcinoma refractory [5]. For confirmation of a diagnosis of primary [3]. Epidermoid carcinoma includes squamous, basal, and SCC of the breast, the following three criteria must be ful- transitional cell carcinomas. It was not recognized as a dis- filled: absence of an associated primary SCC in a second site, tinct entity till 2000. WHO 2012 classified metaplastic breast the absence of skin involvement, and a clear predominance carcinoma as invasive breast cancers with squamous or mes- (>90%) of areas with SCC at histologic examination. enchymal components with elements of spindle, chondroid, There are different hypotheses to explain the histogenesis osseous, and rhabdomyoid cells mixed with the usual cell of squamous cell carcinoma of the breast. It may arise de type [4]. Depending on the cellular behavior, it can be either novo from epithelium lining of the breast or present as a low-grade tumors (low-grade adenosquamous carcinoma or small foci in preexisting adenocarcinoma or deep-seated low-grade spindle cell carcinoma) or high-grade tumors epidermal cyst [6, 7]. (high-grade squamous cell or high-grade spindle cell). In either case, they express heterogeneous somatic muta- Broadly, it is categorized under 3 categories: first, meta- tions [8, 9]. These mutations are different from that of triple plastic carcinoma of no specific type that includes low- negative breast cancer. In one of the study aberrations on 2 Case Reports in Oncological Medicine PIK3CA/PIK3R1 and Ras-Map kinase pathway in 61% and 25%, respectively, in addition to increased frequency of TP53 (64%) and TERT promoter (25%), mutations in com- parison to triple negative carcinomas have been reported. In the other study, metaplastic breast cancer was found to harbor complex mutations leading to activation of the PI3K/AKT/mTOR pathway (57% vs. 22%) and canonical Wnt pathway (51% vs. 28%) as opposed to triple negative breast cancer. Other additional mutations like ARID1A (11%), FAT1 (11%), PTEN (11%), PIK3CA (29%), and PIK3R1 (11%) are expressed in comparison to TN breast cancer. Interestingly, it was found that PIK3CA mutations were absent in MBCs with chondroid metaplasia [10]. Though they have very poor prognosis, the determinant of the prognosis is not clear. 2. Case No. 1 A 39-year-old African American female presented to her pri- Figure 1: Sonogram of the left breast showing hypoechoic lesion. mary care physician with a palpable lump in her left breast. Her past medical history includes hypertension, diabetes mellitus, hyperlipidemia, and seizure. She smoked half a pack of cigarette for the past 16 years. The family history was noncontributory. Ultrasound (Figure 1) and mammogram (Figure 2) of the left breast reported a 2.5 cm lobulated hypoechoic lesion with well-demarcated borders and poste- rior acoustic enhancement suggestive of a complicated cyst. The bilateral breast MRI (Figure 3) that was done 3 weeks later revealed a left retroareolar 3 8×3 7× 3 5cm mass com- plex, heterogeneous with rim enhancement. No other mass or lymphadenopathy was seen. An ultrasound-guided biopsy revealed triple negative, moderately differentiated invasive left breast ductal carcinoma. The right breast was unremark- able. She underwent modified radical mastectomy and lymph node dissection with tissue expander placement 6 weeks after her first ultrasound. The final pathology revealed a 5.5 cm primary invasive metaplastic ductal carcinoma (Figure 4). The histologic grade was 3 with squamous differentiation and was triple negative (Figure 5). Immunohistochemistry was positive for E-cadherin and focally positive for GATA which indicated ductal origin. p63 and cytokeratin 5/6 were Figure 2: Mammogram of the left breast. positive in favor of metaplastic squamous cell differentiation. Proliferative index Ki-67 was >40%. All of the six nodes were negative for a tumor. The rapid growth of the tumor from the time of the diagnosis to the time of surgery explains the aggressive nature of this group of the invasive disease. The final stage was IIB (T3N0MX) metaplastic breast cancer. The patient received adjuvant chemotherapy with dose-dense AC-T (Adriamycin and cyclophosphamide followed by paclitaxel). After completion of chemotherapy, the patient underwent whole breast radiotherapy. Eight months post treatment, the patient is in remission and has no signs of recurrence. 3. Case No. 2 A 53-year-old female with a history of abdominal extra- adrenal paraganglioma, status postsurgical removal, endome- triosis, hypothyroidism, HTN, and thyroid nodule noticed a Figure 3: MRI left breast. Case Reports in Oncological Medicine 3 Figure 4: High-grade features with cell atypia. Figure 6: Left breast sonogram showing a cystic mass. Figure 5: Cell atypia with necrosis. left breast lump for a month during her breast self-exam. On the physical exam at the oncology office, her breast was sym- metrical. There were no skin or nipple changes. A mass of 2 ×2cm and 5 cm from the nipple at 5:00 PM was appreciated with no evidence of axillary lymphadenopathy. She promptly underwent a sonogram (Figures 6 and 7) and mammogram that revealed a heterogeneous breast, and corresponding to the palpable abnormality was a large complex cystic mass measuring 2 7×2 4× 2 6cm with a thick wall with enhanced through transmission and some internal vascularity. She underwent lumpectomy. The gross specimen was described as a 5 5×5×5cm mass with a centrally located cystic hemor- rhagic tumor which measured 3.3 cm in the greatest dimen- sion and negative margin. It was reported as high-grade Figure 7: Left breast mammogram. metaplastic carcinoma (3.3 cm), with sarcomatoid subtype and osteoid matrix production, and high-grade DCIS. Immu- nostaining for estrogen and progesterone receptors and HER2 was negative. The Ki-67 proliferation index was mark- edly elevated to 90%. The area of squamous cell carcinoma was positive for p63 and p40. The sarcomatoid area was neg- ative for cytokeratin (CK AE1/3). On her follow-up clinic visit at 4 weeks post lumpec- tomy, the mass was felt on the surgical site on the physical exam. MRI bilateral breasts showed an enhancing mass of maximal dimension of 1.7 cm and subtle asymmetric left axillary tail lymph node 1 4×0 9cm (Figure 8). Staging CT chest/abdomen/pelvis was negative except for the left breast mass. The patient underwent mastectomy and axil- lary lymph node dissection. Post mastectomy, the gross specimen was reported as a Figure 8: MRI left breast. firm, cystic, hemorrhagic tumor with 4 8×4 5 and 4 cm in dimension located 2.5 cm from the closest inked margin. HER2 status were negative. The patient was scheduled to Pathology description was invasive breast cancer with oste- oid formation (metaplastic) features, grade 3 with no lymph start on dose-dense 4 cycles of AC (Adriamycin and cyclo- vascular invasion and negative margin, and DCIS 0/15 lymph phosphamide) followed by paclitaxel and carboplatin. After node was negative for malignancy. Hormonal receptor and 2 cycles of AC, she was admitted with a chest pain. CT chest 4 Case Reports in Oncological Medicine showed a new mass 3.9 cm complex nodule within the left axilla and 1.8 cm circumscribed nodule within the lateral aspect of the left breast. The biopsy of the lymph node was suggestive of high-grade sarcoma (Figures 9 and 10) with a positive stain for AE1/AE3, CK7 (rare), p63 (rare), CDX2 (focally weak), GATA-3 (rare), and PAX-8 (weak) and nega- tive for CK20, TTF1, Napsin A, S100, GCDFP-15, ER, CA125, mammaglobin, and CEA monoclonal. An additional stain was negative for CD117 and focally positive for DOG1. The patient underwent further resection of the chest wall mass and axillary lymph node. Pathology disclosed a gross specimen of 1.8 cm chest wall lesion and 3 0×3×2 5cm axillary mass with four additional nodules up to 0.5-0.7 cm Figure 9: Cells with sarcomatoid differentiation. with histological similarity to the first tissue biopsy and Ki of >90. Next generation sequencing was negative for any mutations. Post resection, she received radiation without any signs of recurrence. 4. Discussion It is a well-established fact that metaplastic breast cancer is one of the rare entities. The pathogenesis of metaplastic squamous cell carci- noma of the breast has evolved in the recent few years as our understanding of genetic and nongenetic heterogeneity Figure 10: Lymph node biopsy—lymphocyte aggregates and affecting phenotypical behavior of this type of cancer has adjacent tumor cells. broadened. Some authors suggest that it originates from squamous metaplasia [11–14] which is found in the epithe- lium of the cyst, fibroadenomas, phyllodes tumors, or papil- breast present as a larger primary tumor with higher histolog- lomas or chronic abscess [15] whereas others believe that it ical grade and lower incidence of axillary node involvement. arises from myoepithelial cells. Cases were reported of squa- Radiologically, no typical mammographic appearances are mous cell carcinoma on a patient with previous history of found and they lack microcalcifications in most cases [23, chemotherapy and radiation chemotherapy for breast cancer 24]. Cystic lesions are characteristic presentations of SCC [16] and with breast implants [17]. in more than 50% of cases. The definite role of PET CT on In general, DNA array and immunohistochemistry are squamous breast cancer has not been defined yet [25, 26]. performed in addition to histopathology to subdivide breast Due to rarity of this tumor, the most appropriate thera- cancer into 3 broad categories: basal, luminal, and HER over- peutic regimen for SCC of the breast is not defined [27]. Till expression. Though metaplastic squamous cell carcinoma is date, there is no specific guideline for the treatment [28]. mostly hormone negative [18], specific immunostaining is Though chemotherapy for metaplastic breast cancer largely unknown. In the past, there have been some attempts to aligns with invasive ductal cancer, the 3-year disease-free sur- understand the molecular biology of this group of cancer vival rate is poor in comparison to IDC [29]. Due to hetero- which would help clarify the treatment approach [19]. Pure geneity of the tumor, the historical therapy has failed to and metaplastic SCC resemble phenotypically to basal origin: achieve a prolonged response [30]. Resistance to chemother- they never expressed ER (estrogen receptor) or PR (proges- apy is likely due to complex genetic and nongenetic makeup. terone receptor); are HER2-negative in 93% of cases; exhib- So far, the response to chemotherapy has been different from ited positivity for CK 5/6 (cytokeratin) and EGFR in 75% case to case, and some respond with neoadjuvant chemother- and 85%, respectively, and p63 in 70% of cases; and display apy [31, 32]. a high proliferative index. However, expression profile of Overexpression of EGFR was found in a metaplastic SCC of the breast was markedly different from that of IDC breast [33] potentiating the role of protein kinase inhibitors (invasive ductal carcinoma). Additionally, it was found that against EGFR. HPV infection is not associated with SCC of the breast. As mentioned earlier, PIK3 inhibitors and mTOR inhib- Metaplastic breast cancer harbors different complex itors in mesenchymal metaplastic breast cancer have shown mutations. Recently, aberrations in the PIK3/AKT/mTOR promising results in early-phase trials. pathway are found more frequently in mesenchymal subtype of metaplastic breast cancers. Clinical trials targeting this 5. Conclusion pathway in combination with chemotherapy have demon- strated very good response [20–22]. Metaplastic squamous cell breast cancer is a rare malignancy. Up to 30% of the tumor is found to have lymph node pos- It appears large and cystic with the absence of microcalcifica- itive even though lymphatic spread is rare. The SCC of the tions on imaging. It usually has a higher histological grade Case Reports in Oncological Medicine 5 and negative hormonal and HER2 status with lower inci- [13] K. A. Behranwala, N. Nasiri, N. Abdullah, P. A. Trott, and G. 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