Compiled and organized: HadronsInvasive breast cancer.
(3) High-grade triple-negative tumors
High-grade triple-negative tumors are a high-risk condition, especially when this disease is diagnosed in CNB, and patients may require preoperative (neoadjuvant) chemotherapy. Although the misdiagnosis and misjudgment of lesions mentioned above in this article also have an impact on clinical management, the misdiagnosis of high-grade triple-negative breast cancer has the greatest impact. Therefore, before the pathologist signs the pathology report of breast cancer** sex markers, it is necessary to review the HE section to ensure that the morphological characteristics are consistent with the diagnosis of high-grade triple-negative breast cancer.
In classic triple-negative breast cancer, the tumor cells are patchy, with large, pleomorphic nuclei, a large number of nuclei**, and large necrosis and significant lymphocyte infiltration are common. In many cases, there may be no or only a few cases of DCIS. Given its morphologic high-grade and immunohistochemical triple-negative phenotype, it may be necessary to distinguish several lesions such as epithelioid angiosarcoma, high-grade B-cell lymphoma, and metastatic tumors from other sites (e.g., metastatic melanoma).
First and foremost, it is important to know the patient's history of breast cancer or other cancers, which is especially critical in the differential diagnosis of triple-negative breast cancer. If there is a history of surgery and radiation therapy for breast cancer, the possibility of angiosarcoma should be considered. If there is a history of other cancers morphologically high-grade epithelioid, a breast CNB evaluation should be performed, and morphological comparisons with the primary tumor should be considered if necessary.
In addition to the history, there are morphological clues that suggest that we consider a disease other than triple-negative breast cancer. Any unusual morphological findings, or features that differ significantly from those of typical triple-negative breast cancer, are justified by immunohistochemistry, such as the presence of a large number of red blood cells or vague luminal structures, pigmented, plasmacytoid cells, and a nucleus with significant eosinophilic nucleoli. The presence of high-grade DCIS supports the diagnosis of triple-negative breast cancer, but the absence of this does not exclude triple-negative breast cancer.
The routine use of "breast markers" such as GCDFP-15, Mammaglobin, and GATA3 is not recommended because most of the cancers that occur in the breast can be easily identified as primary breast cancers and can be confirmed by hormone receptor testing and HER2 testing. However, triple-negative breast cancer deserves special attention and immunohistochemistry: it is first confirmed to be carcinoma (CK positive), and then it is confirmed to be breast**. SOX10 and TRPS1 are more meaningful in some cases because of their higher sensitivity and specificity in triple-negative breast cancer. However, it should be noted that SOX10 does not rule out metastatic melanoma and should be used in combination with CK.
Epitheloid angiosarcoma
Breast angiosarcoma is uncommon, and primary angiosarcoma is even rarer. Radiotherapy-induced (secondary) angiosarcoma is more common;The tumour is generally located in the breast and subcutaneous tissues, rather than within the breast parenchyma. Primary angiosarcoma of the breast is usually located within the parenchyma of the breast.
High-grade epithelioid angiosarcoma mimics primary breast carcinoma in CNB specimens. In addition to a history of breast radiotherapy, secondary angiosarcoma is generally accompanied by relevant manifestations of the breast**, such as purple plaques or papules, abrasion-like changes**, which may be important clues for an accurate diagnosis if these findings are noted in the pathology application. Knowing that the location of the tumour is superficial rather than deep in the breast is also a useful clue to the diagnosis.
Microscopic examination of angiosarcoma showed solid lamellar tumor cells with bleeding areas and vague luminal fociIn some cases, the nucleus of angiosarcoma is very predominant, and it is almost "extremely atypical" for non-specific types of invasive ductal carcinoma. The combination of these clinicopathologic features and immunohistochemistry, including CK and vascular markers, supports the diagnosis. It is important to note that angiosarcomas, especially epithelioid angiosarcomas, can positively express CK (eg, AE1, AE3, CAM5.)2), so immunohistochemistry is recommended for testing a panel of markers, rather than a single "definitive or exclusionary" CK. Vascular markers ERG and CD31 were diffuse and strongly positive, and CD34 and FLI1 were coloration of varying degrees. Myc is expressed in secondary angiosarcoma, which is consistent with C-Myc amplification in FISH.
Figure 13Epitheloid angiosarcoma of the breast with a large number of red blood cells;In this case, vascular markers were positive and CK was negative in immunohistochemistry.
Metastatic melanoma
In such cases, a good history is important to avoid misdiagnosis. If you do not know the medical history, it is important to keep in mind that you must have a broad perspective in the evaluation of high-grade breast tumorsCytologically, there may be little difference between triple-negative breast cancer and metastatic melanoma with epithelioid morphology, but significant eosinophilic nucleolar and plasmacytoid features, if present, support the latter. If the pigment is detected, it is further determined whether it is melanocyte granules (black or brown, coarse granular) or hemosiderin (golden-brown spheroids).
Immunohistochemistry is also required for differential diagnosis in this setting. It is important to note that certain melanocyte markers, such as S100 and SoX10, can be expressed in carcinomaIn fact, SOX10 is commonly used to support triple-negative breast cancer as breast**. In addition, malignant melanoma, particularly the epithelioid subtype, rarely expresses certain CK, further compounding the problem. Therefore, a reasonable set of markers including multiple CK, S100, SOX10 and MELAN-A should be selected.
Figure 14Metastatic melanoma morphologically characterized by poorly adherent epithelioid manifestations surrounding the acinar of the mammary gland;In this case, S100 and other melanocyte markers were positive, and CK was negative.
Diffuse large B-cell lymphoma
Primary lymphoma of the breast is extremely rare, accounting for less than 0 percent of all breast malignancies5%。Secondary involvement of the breast in systemic lymphoma is also rare. The lymphoma that most commonly occurs in or involves the breast is diffuse large B-cell lymphoma, which accounts for about 45-70% of primary lymphomas of the breast. The age of onset of this disease has the characteristics of bimodal, which are 30-35 years and 55-60 years old, respectively. For the purposes of this article, more attention is paid to younger patients, who have a higher chance of developing triple-negative breast cancer.
The clinical manifestations of young patients and rapidly growing breast masses are highly suspicious, and CNB examination is usually performed quickly. Histologically, it is manifested that the large tumor cells are distributed in sheets, the nucleus has quite significant pleomorphism, there are significant nucleoli, the number of nuclei is large, and there are lymphocytes, which is easy to be misjudged to be consistent with triple-negative breast cancer. As mentioned earlier, immunohistochemistry must be used to support the diagnosis in this case to avoid misdiagnosis, especially if there is clinical pressure to diagnose it as soon as possible. Immunohistochemistry of multiple CK plus CD20 can be done first, and if the latter is positive, lymphohematopoietic markers can be added.
Figure 15Diffuse large B-cell lymphoma with poor cell adhesion, pleomorphism, and abundant apoptosis and nuclei**;The immunohistochemistry CD20 was positive and CK was negative.
To be continued
Previous review: Reading the literature, learning pathology - breast needle aspiration biopsy traps (1).
Read the literature and learn the pathology - breast needle aspiration biopsy trap (2).
Read the literature and learn the pathology - breast needle aspiration biopsy traps (3).
Read the literature and learn the pathology - breast needle aspiration biopsy traps (4).