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Rare Tumors 2023Metaplastic Breast Cancer (MBC) is a rare group of tumors often presenting as triple-negative. MBC accounts for less than 1% of all breast cancers with the spindle cell...
Metaplastic Breast Cancer (MBC) is a rare group of tumors often presenting as triple-negative. MBC accounts for less than 1% of all breast cancers with the spindle cell variant comprising less than 0.5%. While rare, spindle cell carcinoma is the commonest subtype in the western world. It has a more aggressive biological behavior with increased risk of recurrence and death due to disease compared to triple negative breast cancers. There is no treatment guideline for management of MBC due to the rarity of the disease. Instead, treatment is theorized based off success with other types of aggressive breast and metaplastic cancers of different tissue. We present the first known case report of male spindle cell carcinoma of the breast treated with KEYNOTE-522 regimen. Therapy included a first phase with pembrolizumab (dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin and second phase, with four cycles of pembrolizumab with doxorubicin-cyclophosphamide.
PubMed: 36937820
DOI: 10.1177/20363613231163730 -
Frontiers in Oncology 2023Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and...
BACKGROUND
Metaplastic breast cancer (MBC) is a rare breast tumor and the prognostic factors for survival in patients still remain controversial. This study aims to develop and validate a nomogram to predict the overall survival (OS) of patients with MBC.
METHODS
We searched the Surveillance, Epidemiology, and End Results (SEER) database for data about patients including metaplastic breast cancer and infiltrating ductal carcinoma (IDC) from 2010 to 2018. The survival outcomes of patients between MBC and IDC were analyzed and compared with the Kaplan-Meier (KM) method. MBC patients were randomly allocated to the training set and validation I set by a ratio of eight to two. Meanwhile, the performance of this model was validated again by the validation II set, which consisted of MBC patients from the Union Hospital of Fujian Medical University between 2010 and 2018. The independent prognostic factors were selected by univariate and multivariate Cox regression analyses. The nomogram was constructed to predict individual survival outcomes for MBC patients. The discriminative power, calibration, and clinical effectiveness of the nomogram were evaluated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the decision curve analysis (DCA).
RESULTS
MBC had a significantly higher T stage (T2 and above accounting for 75.1% vs 39.9%), fewer infiltrated lymph nodes (N0 accounted for 76.2% vs 67.7%), a lower proportion of ER (22.2% vs 81.2%), PR (13.6% vs 71.4%), and HER-2(6.7% vs 17.7%) positive, radiotherapy(51.6% vs 58.0%) but more chemotherapy(67.5% vs 44.7%), and a higher rate of mastectomy(53.2% vs 36.8%), which was discovered when comparing the clinical baseline data between MBC and IDC. Age at diagnosis, T, N, and M stage, as well as surgery and radiation treatment, were all significant independent prognostic factors for overall survival (OS). In the validation I cohort, the nomogram's C-index (0.769 95% CI 0.710 -0.828) was indicated to be considerably higher than the standard AJCC model's (0.700 95% CI 0.644 -0.756). Nomogram's great predictive capability capacity further was supported by the comparatively high C-index of the validation II sets (0.728 95%CI 0.588-0.869).
CONCLUSIONS
Metaplastic breast cancer is more aggressive, with a worse clinical prognosis than IDC. This nomogram is recommended for patients with MBC, both American and Chinese, which can help clinicians make more accurate individualized survival analyses.
PubMed: 36937402
DOI: 10.3389/fonc.2023.1030124 -
Head and Neck Pathology Mar 2023Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the... (Review)
Review
BACKGROUND
Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the thyroid gland. In addition, other lesions can contain cells that mimic oncocytes (pseudo-oncocytes); these can be of epithelial or non-epithelial origin.
METHODS
Review article.
RESULTS
Oncocytic metaplasia is common in seromucinous glands throughout the upper aerodigestive tract, most notable in the oral cavity, nasopharynx and larynx. The main oncocytic salivary gland neoplasms are Warthin tumor and oncocytoma. Infarction of Warthin tumor may lead to recognition difficulties. Oncocytic subtypes of mucoepidermoid carcinoma and intraductal carcinoma have morphologic and immunohistochemical features that allow distinction from major oncocytic entities. Oncocytic thyroid tumors include adenoma, carcinoma (follicular, papillary and medullary), along with poorly differentiated tumors. Oncocytic papillary sinonasal and middle ear tumors must be distinguished from low grade adenocarcinomas. Pseudo-oncocytic entities include paraganglioma, Langerhans cell histiocytosis, giant cell tumor, rhabdomyoma, and metastatic tumors.
CONCLUSIONS
Correct diagnosis of oncocytic head and neck lesions requires a knowledge of the spectrum of possible entities, their characteristic sites of occurrence, architecture, histomorphology, and immunohistochemistry. Oncocytic subtypes of several newly described entities are now recognized. Both epithelial and non-epithelial mimics of oncocytes exist. The molecular features of oncocytic tumors can be helpful in their diagnosis and understanding their pathogenesis.
Topics: Humans; Oxyphil Cells; Adenolymphoma; Salivary Gland Neoplasms; Salivary Glands; Adenoma, Oxyphilic
PubMed: 36928735
DOI: 10.1007/s12105-022-01520-y -
Journal of Surgical Case Reports Mar 2023A 68 year-old woman with no significant medical history discovered a lump incidentally in her left breast. The patient's initial imaging revealed a 4.6-cm irregular...
A 68 year-old woman with no significant medical history discovered a lump incidentally in her left breast. The patient's initial imaging revealed a 4.6-cm irregular mass at 11:00 categorized as a BI-RADS 5 as well as an enlarged axillary lymph node and an area of 2.5 cm of heterogeneous calcifications in the 3 o'clock position. The 4.6-cm lesion was revealed to be infiltrating ductal carcinoma with a squamous component, mixed metaplastic carcinoma, which was strongly ER (100+)/PR (100+) positive, HER-2/Neu negative on FISH. The 2.5-cm calcifications were ductal carcinoma . The patient completed neoadjuvant chemotherapy, and had an excellent response. After further discussion, the patient elected for breast conservation therapy and underwent a left wireless localized partial mastectomy with a left axillary dissection. Surgical pathology revealed a near complete pathologic response with only 8-mm residual tumour as well as a negative conversion of the clipped axillary node.
PubMed: 36926632
DOI: 10.1093/jscr/rjad144 -
Chronic Diseases and Translational... Mar 2023The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific gene...
BACKGROUND
The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific gene rearrangement and histological characteristics may be the solution.
METHODS
Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs.
RESULTS
There were 16 MECs; 62.5% were rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were rearranged. For the classic and nonclassified MECs without rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs ( = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for rearrangement.
CONCLUSION
The application of combining rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.
PubMed: 36926257
DOI: 10.1002/cdt3.55 -
Cancers Mar 2023Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of...
BACKGROUND
Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified.
METHODS
We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis.
RESULTS
The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, = 0.1340) after PSM.
CONCLUSION
Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.
PubMed: 36900347
DOI: 10.3390/cancers15051556 -
Archives of Pathology & Laboratory... Dec 2023Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by...
CONTEXT.—
Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences.
OBJECTIVE.—
To genetically characterize FLMC.
DESIGN.—
To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases.
RESULTS.—
All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden.
CONCLUSIONS—
We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.
Topics: Humans; Female; DNA Copy Number Variations; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Breast Neoplasms; Carcinoma; TOR Serine-Threonine Kinases; Mutation; Fibroma; Telomerase
PubMed: 36897999
DOI: 10.5858/arpa.2022-0159-OA -
Modern Pathology : An Official Journal... May 2023Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a...
Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.
Topics: Humans; Female; Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms; Triple Negative Breast Neoplasms; Carcinoma in Situ; Transcription Factors; Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Repressor Proteins
PubMed: 36870308
DOI: 10.1016/j.modpat.2023.100125 -
Modern Pathology : An Official Journal... Jun 2023Acinic cell carcinoma (AciCC) is a tumor that is recognized in both the breast and salivary glands. Recently, the recurrent genomic rearrangement, t(4;9)(q13;q31) was...
Acinic cell carcinoma (AciCC) is a tumor that is recognized in both the breast and salivary glands. Recently, the recurrent genomic rearrangement, t(4;9)(q13;q31) was identified in salivary AciCC that results in constitutive upregulation of the nuclear transcription factor NR4A3, which can be detected by immunohistochemistry. In this study, we sought to evaluate NR4A3 expression in breast AciCC using immunohistochemistry. Strong and diffuse nuclear staining was considered a positive result. Sixteen AciCCs were studied, including 8 pure AciCCs and 8 AciCCs admixed with other types (invasive carcinoma of no special type in 5 cases and metaplastic carcinoma in 3 cases). All 16 AciCCs showed negative results for NR4A3 expression. Four cases with available material were evaluated for rearrangements of the NR4A3 gene by fluorescence in situ hybridization and no rearrangements were observed. Whole-genome sequencing of 1 AciCC revealed a TP53 splice-site mutation, high levels of genomic instability, and genomic features of homologous recombination DNA repair defects; a structural variant analysis of this case did not reveal the presence of a t(4;9) rearrangement. We conclude that breast AciCCs consistently lack NR4A3 rearrangement or overexpression, unlike most of the salivary AciCCs, and that consistent with previous results, breast AciCCs are associated with genomic alterations more similar to those seen in triple-negative breast carcinomas than salivary gland AciCCs. These results suggest that unlike other salivary gland-like tumors that occur in the breast, the molecular underpinnings of the salivary gland and breast AciCCs are different and that the salivary gland and breast AciCCs likely represent distinct entities.
Topics: Humans; Carcinoma, Acinar Cell; In Situ Hybridization, Fluorescence; Salivary Gland Neoplasms; Carcinoma; Gene Rearrangement; Biomarkers, Tumor; DNA-Binding Proteins; Receptors, Steroid; Receptors, Thyroid Hormone
PubMed: 36828363
DOI: 10.1016/j.modpat.2023.100144 -
Case Reports in Oncology 2022Fibromatosis-like metaplastic carcinoma is a special variant of spindle cell carcinoma, a type of metaplastic carcinomas. It has a favorable prognosis, unlike other...
Fibromatosis-like metaplastic carcinoma is a special variant of spindle cell carcinoma, a type of metaplastic carcinomas. It has a favorable prognosis, unlike other metaplastic carcinomas, with a particular clinical behavior characterized by frequent local recurrence, the meager potential for axillary lymph nodes, and distant metastases. We presented the case of a 51-year-old female with a large mass on the left breast, which was successfully removed by surgical resection. The pathological diagnosis was fibromatosis-like metaplastic carcinoma with the help of morphology and immunohistochemistry adjustment.
PubMed: 36825103
DOI: 10.1159/000526535