Invasive Ductal Carcinoma of No Special Type/Not Otherwise Specified Type
Invasive breast carcinoma of the "no special type" (NST) or "not otherwise specified" (NOS) variety makes up the largest single category of invasive breast carcinomas, accounting for between 47% and 75% of all invasive breast cancers, depending on the series.19,20 These tumors may present as a clinical lump, or be clinically inapparent and detected by a variety of imaging techniques including mammography, ultrasonography, or magnetic resonance imaging. The designation of a particular invasive mammary carcinoma as NST/NOS type is one of exclusion, and does not refer to a particular type of invasive ductal carcinoma but rather to an invasive ductal carcinoma that cannot be classified histologically as a particular special type of invasive ductal carcinoma based on current morphologic classification schemes (ie. the subtypes described later in the chapter). As such, NST tumors are a heterogeneous group of carcinomas of varying histologies and grades. The WHO definition of an NST tumor requires a nonspecial-type pattern to be present in greater than 50% of the tumor after a thorough examination of representative histologic sections. If an NST pattern is present in 10% to 49% of the tumor, the carcinoma is classified as mixed NST and special type. For an invasive carcinoma to classify as a special-type tumor, at least 90% of the tumor must show the appropriate special-type histomorphology. NST tumors appear to make up a lower proportion (approximately 40%) of small, screen-detected invasive carcinomas, and there may be a slightly increased frequency of NST tumors below the age of 35 years compared with older patients, who have an increased proportion of lobular and other special-type carcinomas.21
Gross and Microscopic Pathologic Findings
Generally, NST carcinomas form a solid, gray-white nodular mass that may be well circumscribed or have ill-defined, infiltrative borders on cut section. The descriptive terms "scirrhous" or "stellate" carcinoma refer to a carcinoma with extensive fibroelastosis that manifests grossly as firm yellow-white streaks on cut section.
Scirrhous carcinomas demonstrate a central solid mass that radiates irregularly into the surrounding fatty breast tissue. Tumor necrosis may be found in large, rapidly growing tumors that are outgrowing their blood supply, and this necrosis grossly presents as soft, white chalky areas. Gross cystic degeneration in NST tumors is rare.
The size of these tumors varies greatly, ranging from a few millimeters to over 10 centimeters; on average, the size of these tumors is approximately 2 cm in maximal dimension.
Microscopically, NST invasive ductal carcinoma is characterized by a growth of malignant epithelial cells organized into cohesive cords, nests, sheets, and tubules that infiltrate breast stroma in a disorganized and irregular fashion. The stroma within a particular tumor may be densely fibrotic or minimal in amount. The tumor cells of NST tumors show a varying degree of cytologic atypia, and variable amounts of inflammation may be present within/around the tumor mass. Immunostaining for myoepithelial cells (ie, with smooth-muscle myosin heavy-chain, calponin, or P63) or basement membrane (collagen IV) is often a useful adjunctive diagnostic technique to confirm the lack of a myoepithelial cell layer or basement membrane, a finding critical to the diagnosis of stromal invasion. Ductal carcinoma in situ (DCIS) is found in approximately 80% of cases either within or around the tumor mass, and is usually of intermediate or high grade.22 Approximately 70% to 80% of NST tumors are ER positive, 60% PR positive, and 15% to 30% are HER-2/neu positive.
The prognosis of a particular NST tumor is dependent on the traditional prognostic indicators such as size, tumor grade, lymphovascular invasion, and lymph node status. Overall, NST tumors show a 35% to 50% 10-year survival without adjuvant treatments. Following surgical excision with clear margins, treatment specifics (ie, postoperative radiation and chemotherapy) are determined by the traditional prognostic indicators noted earlier, as well as ER, PR, and HER-2/neu status of the tumor.
Invasive Lobular Carcinoma
Invasive lobular carcinoma is the second most common type of invasive breast carcinoma after NST invasive duct carcinoma. The reported frequency is between 5% and 15%.23,24 Factors that contribute to this range include the wide range of morphologic features represented by invasive lobular carcinoma and differing criteria used for diagnosis, and the impact of mammographic screening and hormonal therapy. The incidence of invasive lobular carcinoma increased over the time period 1987 to 1999 while the incidence of invasive duct carcinoma remained stable. This increase occurred at a time of increased use of combined replacement hormonal therapy and it is postulated that the increased incidence of invasive lobular carcinoma is associated with this use.25 An increased proportion of lobular carcinoma has been reported in populations at higher risk of breast cancer.26
Several morphologic patterns of invasive lobular carcinoma are recognized, with the most common type termed the classic type. Other types are termed variants of invasive lobular carcinoma and include mixed, solid, alveolar, signet ring, histiocytoid, tubulolobular, and pleomorphic carcinoma. The types are differentiated based on histologic morphology, and some subtypes appear to be associated with differences in clinical outcome.
Patients with invasive lobular carcinoma tend to be slightly older than those with nonlobular invasive carcinoma (mean age reported as 57 years23 and 64 years27). On mammography, architectural distortion is more common and microcalcification less common with invasive lobular carcinoma compared to invasive duct carcinoma.1
Gross and Microscopic Pathologic Findings
Invasive lobular carcinoma tends to be larger at diagnosis than nonlobular invasive carcinoma,23 with 19% of invasive lobular carcinoma larger than 5 cm in one series.23 Increasing tumor size has been correlated with increasing grade.27 The gross appearance may be indistinguishable from invasive duct carcinoma with formation of a stellate mass, or may be more ill defined resulting in an area of vague induration that is difficult to delineate on gross examination. In the latter situation the invasive carcinoma may be much more extensive on microscopic examination than anticipated from gross examination.
A number of morphologic features distinguish invasive lobular from invasive duct carcinoma on microscopic examination; however, it is the combination of features that allows this distinction, as individually none of these features are specific for a lobular type in routine stains.28 Some invasive carcinomas (approximately 3-4%28) have features indeterminate between ductal and lobular type on routine stains. To accommodate this difficulty in classification, some pathologists have used terms such as "invasive carcinoma with both ductal and lobular features." This is in addition to, and distinct from, mixed type of invasive carcinomas with features that can be identified as ductal in type in some areas and lobular in type in other areas—estimated to be 5% of invasive carcinoma.1 E-cadherin immunostaining is proving increasingly helpful in assigning a morphologic type since the majority of invasive lobular carcinomas do not show cytoplasmic membrane staining while invasive ductal carcinomas do.11,27
To qualify as an invasive lobular carcinoma, more than 90% of the carcinoma must show one of more patterns of lobular carcinoma, in keeping with the classification of other types of invasive mammary carcinoma. To qualify for a particular subtype there are not uniformly agreed-upon criteria, although an 80% threshold has been suggested (> 80% of a particular pattern required for a particular subtype designation, if < 80% considered mixed type).29
The most common subtypes of invasive lobular carcinoma are classical and mixed subtypes, representing 55% and 34% of a series of invasive lobular carcinoma, respectively.24
Some components of the grading scheme appear less applicable to invasive lobular carcinoma than nonlobular since the majority of invasive lobular carcinomas have a solid growth pattern and little mitotic activity.24 It is, however, recommended that invasive lobular carcinoma is graded using the same grading scheme as nonlobular carcinoma. The majority of invasive lobular carcinomas are grade II (76%2) with a small proportion being grade I or III (12% each24). Tubulolobular carcinoma and some classic invasive lobular carcinoma are grade I, pleomorphic invasive lobular carcinoma is grade II or III, and other classic invasive lobular carcinoma and variants are grade II. Invasive lobular carcinoma has been reported to be associated with an increased risk of multicentricity and bilaterality; however, some studies, both clinical and imaging, have not shown a significant difference in the incidence of multicentricity and bilaterality between invasive lobular carcinoma and invasive duct carcinoma.1,23 Invasive lobular carcinoma is more frequently ER positive than nonlobular carcinomas; the positivity rate ranges from 70% to 100%.1,27 PR positivity is similar to invasive duct carcinoma, in some reports positive in 60% to 70% of cases1; however, in some series invasive lobular carcinoma is more frequently PR positive than invasive duct carcinoma (positive in 85-90%27). HER-2 protein overexpression is less likely than with invasive duct carcinoma, with some reported series of invasive lobular carcinoma entirely negative (0% of 50 cases27); however, HER-2 protein overexpression have been reported in 81% of 38 cases of pleomorphic variant of invasive lobular carcinoma.30
Classic Invasive Lobular Carcinoma
Classic invasive lobular carcinoma is the most common type of invasive lobular carcinoma. The tumor cells are small, uniform, and monotonous and infiltrate in a dispersed, noncohesive manner (Fig. 20-5). The cells often show a linear growth pattern (referred to as "single file") and grow around structures in concentric lines of cells referred to as a "targetoid" growth pattern. The cells may percolate into fatty tissue between fat cells without associated stromal fibrosis. This growth pattern may result in the invasive carcinoma being more extensive than grossly estimated.
Invasive lobular carcinoma, classic type (H&E stain, 200×). The malignant cells are small and bland. The cells do not form cohesive cell groups; in areas the cells are in linear arrangement (single file). In one area tumor cells can be seen extending into fat.
Small numbers of invasive tumor cells, particularly if admixed with lymphocytes or reactive changes, may easily be overlooked. These cells are keratin positive, which can be very helpful both to identify the existence of these cells and confirm that these are epithelial in nature.
Pleomorphic Variant of Invasive Lobular Carcinoma
The tumor cells have the pattern of infiltration of classic lobular carcinoma but are larger, more pleomorphic, and have a tendency to aggregate, with features that may overlap with invasive ductal carcinoma (Fig. 20-6).30,31 Apocrine features may occur in invasive lobular carcinoma; this tends to be present in the pleomorphic variant,31 and these cells will be GCDFP-15 positive. Histiocytic features are also described in this variant.31
Invasive lobular carcinoma, pleomorphic type (H&E stain, 200×). In contrast to Figure 20–5, the tumor cells are more cohesive, forming small cell groups, and are larger with more nuclear variability and atypia.
There are no specific criteria for how large or atypical the tumor cells should be to qualify for this type, which will account for some variability in diagnosis. In general, the degree of mitotic activity identified is greater than with classic type. The use of E-cadherin stain allows identification of this as lobular type, which may otherwise have been interpreted as ductal type.
Tubulolobular Variant of Invasive Lobular Carcinoma
The tubulolobular variant of invasive lobular carcinoma is a rare variant with features of both tubular and lobular carcinoma. The pattern of infiltration is reminiscent of invasive lobular carcinoma with an infiltrative growth pattern and cells arranged in single file or in a targetoid growth pattern; however, the tumor cells also form small cohesive cell groups and microtubules.32 This has traditionally been classified as a variant of invasive lobular carcinoma; however, recently this type of invasive carcinoma has been found to show a ductal staining pattern with E-cadherin stain.32 Further studies will clarify if this should continue to be considered a variant of invasive lobular carcinoma or should be reclassified.1
Signet Ring Cell Carcinoma
The presence of some signet ring cells is frequent in forms of invasive lobular carcinoma, but extensive signet ring formation is much less frequent, representing 0.1% to 0.3% of invasive breast carcinoma.28
Solid and Alveolar Variants
In the solid pattern the tumor cells are arranged in loose sheets, while in the alveolar pattern the tumor cells are in small, circumscribed aggregates of 20 or more cells and may simulate in situ lobular carcinoma.
The prognosis for invasive lobular carcinoma has been reported as worse, better, or the same as for invasive duct carcinoma.23 The prognostic value associated with tumor stage and lymph node status is applicable with invasive lobular carcinoma,23 but some have found less prognostic value with grade for invasive lobular carcinoma than with nonlobular types,23 possibly due to difficulty applying the grading scheme. With strict adherence to the criteria for grading, others have found histologic grade to be of independent prognostic value.24
The pleomorphic variant of invasive lobular carcinoma is associated with more aggressive clinical behavior than the classic type.31
Lymphoma is in the differential diagnosis of a breast mass composed of an infiltrate of noncohesive tumor cells. Staining with immunostains for keratin and lack of staining with lymphoid markers will allow this distinction.
Metastatic lobular carcinoma within lymph nodes is less easily recognizable than metastatic ductal carcinoma, as the cells may resemble histiocytes and be misinterpreted as a reactive change. Identification of metastatic lobular carcinoma at frozen section may be particularly difficult. Keratin immunostains may be very helpful in confirming metastatic lobular carcinoma in lymph node.
Tubular carcinoma is a special type of invasive duct carcinoma, which is well differentiated and has a favorable prognosis.
Overall, tubular carcinoma accounts for < 2% of invasive breast cancer.1 The proportion of invasive carcinomas of this type in different series is influenced both by the criteria used for histologic diagnosis and also the method of detection of the carcinoma. Tubular carcinoma is more common in cancers detected by mammographic screening than detected clinically, with the proportion of screen-detected cancers that are tubular carcinomas ranging from 9% to 19%.33 The majority of tubular carcinomas are detected mammographically34 as either a small spiculated mass or parenchymal deformity.35 Patients with tubular carcinoma are similar in age to patients with well-differentiated (grade I) invasive duct carcinoma.36,37
Gross and Microscopic Pathologic Findings
The majority of tubular carcinomas are 1 cm or less in maximum dimension.1,33,36 The mean dimension of tubular carcinoma has not changed over time; however, the mean dimension of invasive duct carcinomas has decreased over time,36 and currently the size of tubular carcinomas is similar to well-differentiated (grade I) invasive duct carcinoma.36
There are no distinguishing characteristics on gross examination.
On microscopic examination, the invasive carcinoma is composed of glands (tubules) within stroma that is cellular and fibroblastic. The glands are open, irregular, and angulate in shape, and are lined by a single layer of epithelial cells, which may have protrusions into the lumen known as "apical snouts." The tumor cells are small and uniform, without high-grade nuclear features, and mitoses are unusual (Fig. 20-7).
Tubular carcinoma (invasive carcinoma of tubular type) (H&E stain, 200×). The malignant cells are very bland in appearance and form well-defined glands. In some areas, the inner (luminal) surface of the glands have protrusions—"apical snouts." The stroma shows some increased cellularity.
All tubular carcinomas are grade I invasive carcinomas, but the reverse is not so (not all grade I invasive carcinomas are tubular). Tubular carcinoma is differentiated from grade I invasive duct carcinoma mainly by the extent of tubule formation; there has not been uniformity in the proportion of carcinoma required to form tubular structures for a diagnosis of tubular carcinoma, which has ranged from at least 75% to 100%.1,37 The dominant current view is that at least 90% of the invasive carcinoma must form tubules to qualify for the designation of pure tubular carcinoma.1,3,37 Invasive carcinoma that is >50% tubular and the remainder cribriform is also classified as pure tubular carcinoma.33 Invasive carcinoma that is 50% to 90% tubular and the remainder of non-cribriform type is classified as mixed type of invasive carcinoma.1,33 Recent attempts have been made to refine the criteria for diagnosis by further evaluating tubule formation and also nuclear atypia and mitotic activity.36,38 Tubular carcinoma has been associated with a high risk of multicentricity (56%) and bilaterality (38%).39 The majority of tubular carcinomas are ER and PR positive, and negative for HER-2 protein over expression.1,39 The differential diagnosis of tubular carcinoma includes benign entities such as sclerosing adenosis and radial scar, and other forms of invasive carcinoma, particularly grade I invasive duct carcinoma of no special type, and also tubulolobular carcinoma. Differentiation from benign entities may be particularly challenging on core biopsies and is greatly assisted by the use of immunohistochemical stains for myoepithelium.
When uniform criteria for diagnosis are used, in comparison with well-differentiated (grade I) invasive duct carcinoma, patients with tubular carcinoma have a lower proportion of axillary node involvement at presentation (12.9% compared to 23.9%), a statistically significant lower rate of local recurrence, and a trend to lower rate of systemic relapse.37 The more restrictive the diagnostic criteria, the better the clinical outcome associated with a diagnosis of tubular carcinoma, with 100% 10-year disease-free survival reported in one series using the most restrictive diagnostic criteria.36
Mucinous (Colloid) Carcinoma
Mucinous carcinomas (also referred to as colloid carcinoma, gelatinous carcinoma, mucous carcinoma, or mucoid carcinoma) contain "large amounts of extracellular epithelial mucous sufficient to be visible grossly, and recognizable microscopically, surrounding and within tumor cells."1 The tumor cells within this mucinous material must also demonstrate a low nuclear grade. As noted previously, by current WHO criteria, at least 90% of tumor must show this histomorphology to be classified as a pure mucinous carcinoma. Tumors that show mucinous differentiation in 50% to 90% of the tumor and/or high-grade nuclear cytology are classified as mixed NST/mucinous tumors, or NST tumors showing mucinous features, a diagnosis that does not connote an improved prognosis as does a pure mucinous carcinoma.
Pure mucinous carcinomas are relatively uncommon, accounting for approximately 2% of invasive ductal carcinomas when strict diagnostic criteria are applied.40 Most studies have noted a higher mean age for women with mucinous carcinoma as compared to patients with nonmucinous carcinoma. Mucinous carcinoma accounts for about 7% of carcinomas in women 75 years or older and only approximately 1% of women younger than 35 years of age.41 The majority of mucinous carcinomas present as a breast mass with mammographically detected microcalcifications occurring in a minority (ie, approximately 40%) of the tumors.42
Gross and Microscopic Features
Grossly, these tumors tend to be relatively well circumscribed and lobulated, with a glistening, mucoid-appearing cut surface. Histologically, the tumor consists of small clusters, nests, and acini of cytologically low-grade malignant epithelial cells floating within lakes of mucin (Fig. 20-8). The mucous is composed of both neutral and acidic mucopolysaccharides. The tumor cells have granular eosinophilic and hyaline cytoplasm, and intracellular mucin may be identified. Argyrophilia (ie, neuroendocrine differentiation) has been identified in up to 25% of mucinous carcinoma on histochemical or immunohistochemical staining, and electron microscopy, but this finding appears to be of no prognostic significance.43 An associated ductal carcinoma in situ component is found in 60% to 75% of cases.44 Immunohistochemical studies have shown that almost 90% of mucinous carcinomas are positive for ER,45 while they tend to be negative for HER-2/neu.
Mucinous (colloid) carcinoma (H&E stain, 100×). Clusters of cytologically low-grade malignant epithelial cells floating in lakes of abundant mucin.
Relative to stage-matched NST invasive ductal carcinoma, mucinous carcinoma has a relatively favorable prognosis. These tumors tend to be axillary lymph-node negative, with the reported frequency of axillary node positivity in series reported in the past 2 decades ranging from 0% to 29%.46 The 15-year disease-free survival rates have been cited in the range of 85% for pure mucinous carcinoma, compared to 63% for invasive ductal carcinomas NST with a mucinous component.47
Metaplasia is the process by which one adult cell type changes into another adult cell type that is not normally present within that tissue. As invasive ductal carcinoma arises from the glandular epithelium of the breast, it usually shows the morphologic features of an adenocarcinoma. In less than 5% of invasive breast carcinomas, some or all of the malignant cells exhibit a nonepithelial or nonglandular growth pattern.48
The term "metaplastic carcinoma" refers to this uncommon, heterogenous group of breast carcinomas, which show a mixed, biphasic (ie, glandular and nonglandular) morphology, or a pure nonglandular morphology with immunohistochemical staining evidence of epithelial differentiation.
Traditionally, metaplastic carcinomas have been divided into 2 groups, those with squamous differentiation and those with pseudosarcomatous differentiation; however, some tumors exhibit both types of differentiation. The metaplastic differentiation may be quite focal or extensively present within an individual tumor, and does not require the 90% or more metaplastic subtype morphology that other special-type carcinomas require for diagnosis.
Squamous differentiation is the most frequent type of metaplasia that has been observed in these lesions, but a variety of mesenchymal differentiation may also be present.
Due to their relative rarity, the diversity of the type and amount of metaplasia that may be present, and a lack of consensus as to terminology, a clinically meaningful pathologic classification system for this group of tumors has proven to be somewhat elusive. The following subclassification of metaplastic breast carcinoma is based largely on morphology and the empiric findings that the specific type of metaplasia present within a tumor influences its biological behavior.
Metaplastic Carcinoma, Squamous Cell Type
There are no clinical features that are specific for metaplastic squamous cell carcinoma of the breast. The age at diagnosis is similar to the age at diagnosis of breast carcinoma generally, and ranges from 31 to 83 years.49 A diagnosis of squamous metaplastic breast carcinoma requires exclusion of cutaneous origin and metastasis from other primary sites, which may include lung, uterine cervix, and urinary bladder. Invasion into the skin and chest wall may make differentiation of secondary skin involvement by a primary breast carcinoma from a carcinoma of cutaneous origin difficult, and requires clinicopathologic correlation. While there are no pathognomonic imaging findings, calcifications may be present associated with tumor necrosis, and cystic degeneration may occur.
Gross and Microscopic Features
Squamous carcinomas tend to be somewhat larger on presentation than other types of breast carcinoma, with nearly half of the tumors being 5 cm or more in maximal dimension.50 These tumors often show central cystic degeneration with necrosis and hemorrhage. Histologically, these lesions are not different from squamous cell carcinomas of other primary sites, most being moderately differentiated (Fig. 20-9). A spindle-cell component may be present that stains positively for either high- or low-molecular-weight keratins. There may be an associated ductal carcinoma in situ component present that helps confirm the primary nature of the tumor. Most tumors have been reported to be ER negative.49,51
Metaplastic carcinoma, squamous cell type (H&E stain, 100×). Malignant ductal epithelium exhibiting focal squamous metaplasia. The squamous cells have "glassy" eosinophilic cytoplasm with intercellular bridges.
Overall, the prognosis of mammary squamous carcinoma does not appear to be different from stage-matched, NST breast carcinomas52; that is, the presence of squamous metaplasia does not appear to significantly influence prognosis.
Metaplastic Carcinoma, Low-Grade Adenosquamous Carcinoma Type
The mean age at presentation in the largest series yet published51 was 54 years, with a range of 33 to 88 years. All patients presented with a palpable mass. The average size of the tumors was 2.5 cm.
Gross and Microscopic Features
The tumors tended to be irregular, tan or pale-yellow mass lesions that were often poorly circumscribed with a stellate, infiltrative character. Histologically, the tumors are composed of infiltrating, compressed, often comma-shaped glandular structures with varying proportions of squamous and glandular elements that sometimes merge into a single structure. The lumina of these structures may contain eosinophilic material and keratinous debris associated with squamous differentiation. The tumor cells are bland with little cytologic atypia and infrequent mitoses. The epithelial components of this neoplasm are typically widely separated by a cellular collagenous stroma that may have an edematous appearance and have a mild lymphocytic infiltrate. An association with sclerosing/papillary lesions and adenomyoepithelioma has been noted. These tumors tend to show no ER or PR positivity. HER-2/neu positivity has been described in less than half of the cases.
Low-grade adenosquamous carcinoma is considered to have a relatively good prognosis compared to NST tumors, with a low rate of lymph node and/or distant metastases noted.53
Metaplastic Carcinoma, Mixed Spindle Cell and Monophasic Spindle Cell Type
This type of metaplastic carcinoma presents as a mass lesion and occurs mainly in postmenopausal females.
Gross and Microscopic Features
These tumors tend to be fairly large, solid, and have a gritty, gray-white appearance, sometimes with foci of necrosis. In Fletcher's series of 29 cases, the tumor size ranged from 1.5 to 15 cm, with a median size of 4.0 cm.54 The tumors may be grossly circumscribed or poorly defined and infiltrative with areas of cystic degeneration/necrosis. The nuclear grade of the spindle cells may be variable, ranging from low-grade to high-grade. The spindle cells tend to be arranged in interlacing fascicles sometimes with a storiform appearance (Figs. 20-10 and 20-11). A component of invasive ductal carcinoma of NST type, or squamous cell carcinoma may be present, and DCIS is identified in a minority of cases. Immunohistochemical staining is pivotal in establishing the epithelial nature of the spindle cells, and may require the use of a wide range of keratin stains (ie, both high- and low-molecular-weight keratins), and often coexpression of vimentin or other mesenchymal markers may be seen. The degree of keratin positivity in the spindle cells ranges from rare scattered cells to diffuse staining of the spindle cells.
Metaplastic carcinoma, mixed spindle cell and squamous type (H&E stain, 100×). This tumor demonstrates malignant spindle cells (which showed keratin positivity by immunohistochemistry) with interspersed areas of squamous differentiation. A focus of ductal epithelial differentiation that is merging with a focus of squamous metaplasia is noted centrally.
Metaplastic carcinoma, pure spindle-cell type (H&E stain, 100×). This breast carcinoma consists virtually entirely of malignant spindle cells, which exhibit areas of keratin positivity by immunohistochemistry.
Immunohistochemical evidence suggesting myoepithelial differentiation has also been noted. These tumors tend to be negative for ER, PR, and HER-2/neu.
Most patients with spindle-cell metaplastic carcinoma have been treated with mastectomy, usually with axillary dissection. Several studies have noted a decreased propensity for axillary lymph node metastases for metaplastic carcinomas in which the spindle-cell component predominates over the epithelial component when compared with usual adenocarcinoma of the breast, and some authors have questioned the utility of axillary lymph node dissection in patients without clinical lymphadenopathy.54,55 Overall, the presence of extensive spindle cell metaplasia may have an adverse influence on prognosis. Spindle-cell metaplastic carcinomas appear to behave aggressively and have a propensity for pulmonary and other visceral metastases.54,55 The effect of radiation and adjuvant chemotherapy on metaplastic carcinoma has not been determined,56 but there is no evidence that they would behave differently than other breast cancers with adjuvant treatment.
Metaplastic Carcinoma, Mixed Epithelial Mesenchymal Type
The patients tend to be postmenopausal and present with a palpable mass.
Gross and Microscopic Features
This group of tumors includes invasive ductal carcinomas with heterologous differentiation that may include a variety of mesenchymal elements such as chondrosarcoma, osteosarcoma, liposarcoma, rhabdosarcoma, fibrosarcoma, or angiosarcoma (Fig. 20-12). Once again, epithelial differentiation may be focal, and require confirmatory immunohistochemical staining. The presence of a DCIS component is helpful in confirming the diagnosis of metaplastic carcinoma. ER, PR, and HER-2/neu tend to be negative.
Metaplastic carcinoma, mixed epithelial/mesenchymal type (H&E stain, 100×). This invasive breast carcinoma demonstrates both osteosarcomatous differentiation (a malignant spindle-cell proliferation with osteoid and bony trabeculae formation) and focal squamous metaplasia (a focus of squamous metaplasia is seen in the mid-central portion of the photograph).
It appears that heterologous metaplasia does not seem to have negative impact on prognosis, with these tumors appearing to behave like a high-grade invasive ductal carcinoma. Most patients in the literature have been treated with mastectomy and axillary dissection, but this diagnosis should not dissuade one from lumpectomy and sentinel lymph node biopsy if caught at an early stage. The effect of radiation and adjuvant chemotherapy on metaplastic carcinoma has not been determined.56