FIGURE 8.1 Adenofibroma of the uterine cervix, papillary fronds, unremarkable fibromatous stroma, and bland endocervical epithelium.
Adenomyoma
Adenomyoma is an uncommon benign neoplasm that is well circumscribed and is usually composed of endometrial-type glands embedded in a stroma that is composed of smooth muscle that occasionally has fibrous areas. The glands are well spaced, without back-to-back arrangement, and variable in distribution, size, and shape (Fig. 8.2, e-Figs. 8.2–8.4). Minor foci of tubal, mucinous, and squamous differentiation can be seen. Rarely, foci of adenocarcinoma can be found (8–10). The smooth muscle component has variable cellularity, ranging from hypocellular, due to hyalinization or edema, to hypercellular, and lacks a distinct arrangement; some tumors have occasional bizarre nuclei. The stromal component can contain endometrial stroma, which is always periglandular, and heterologous elements such as fat and skeletal muscle (8,11). Mitotic activity in both the glandular and stromal components is typically low, although occasional cases can have up to 5 mitoses per 10 HPFs in the stroma or glands. Uterine adenomyomas usually arise in the uterine body in a submucosal location, although a few arise in the cervix or in a mural or subserosal location. Patients range in age from 22 to 64 years with most cases detected during the fifth decade of life. Tumors range in size from 0.3 to 17 cm (8,12). In rare instances, this tumor can be associated with Turner syndrome (13).
FIGURE 8.2 Adenomyoma of the uterine body, irregularly distributed glands with variable shape and size surrounded by smooth muscle stroma.
The differential diagnosis of uterine adenomyoma includes the following:
1.Endometrial polyp: This lacks the very prominent smooth muscle component typically seen in uterine adenomyoma.
2.Leiomyoma with entrapped endometrial glands: This neoplasm shows a few endometrial glands at the periphery. In contrast, uterine adenomyoma shows numerous glands that are distributed throughout.
3.Atypical polypoid adenomyoma: See later discussion.
Endocervical-type adenomyoma is an unusual neoplasm characterized by markedly irregular glands embedded in a stroma composed mostly of smooth muscle with a minor component of fibrous tissue (Fig. 8.3, e-Figs. 8.5 and 8.6). The glands are lined by mucinous epithelium, although minor foci of tubal-type epithelium and endometrial glands, and stroma can be found. Carcinoembryonic antigen (CEA) can be focally expressed. This tumor occurs in the uterine cervix and ranges in size from 1.3 to 23 cm; most cases grow into the cervical canal, although it can also be mural and project into the pelvis from the outer aspect of the cervix. The patients have a mean age of 40 years (range 21 to 55 years) and are usually asymptomatic, but vaginal bleeding or a mucoid discharge can be present. This tumor must be differentiated from minimal deviation adenocarcinoma, and the features that aid in this distinction include gross circumscription, polypoid configuration, less numerous and more evenly spaced glands as compared to minimal deviation adenocarcinoma, and the absence of focal cytologic atypia, perineural or vascular invasion, and desmoplastic reaction as seen in minimal deviation adenocarcinoma (14).
FIGURE 8.3 Adenomyoma of the uterine cervix, irregularly distributed endocervical glands in smooth muscle stroma.
Atypical Polypoid Adenomyoma
Atypical polypoid adenomyoma is characterized by the presence of disorganized hyperplastic glands embedded in a stroma composed of intersecting fascicles of smooth muscle or fibromuscular tissue (Fig. 8.4, e-Figs. 8.7–8.10). The stroma can be exclusively fibromatous in areas (e-Fig. 8.11). The glands are lined by cuboidal, low columnar, or columnar and pseudostratified epithelium, and are variable in size and shape. The epithelium can have atypical nuclei (i.e., round nuclei with an irregular distribution of chromatin and conspicuous nucleoli) and usually there are squamous morules (e-Figs. 8.12–8.14). The hyperplasia can be marked, reaching the threshold for the diagnosis of a well-differentiated endometrial endometrioid adenocarcinoma (i.e., back-to-back glandular arrangement measuring at least 2 × 2 mm) (e-Fig. 8.15). In such a case, we make the diagnosis of endometrial endometrioid adenocarcinoma, International Federation of Gynecology and Obstetrics (FIGO) grade 1, arising in an atypical polypoid adenomyoma. However, some pathologists designate these cases as atypical polypoid adenomyoma of low malignant potential and suggest that a conservative therapeutic approach can be considered because adenocarcinomas arising in these tumors tend to be at most superficially invasive (15). In our opinion, the limited experience with cases of endometrioid adenocarcinoma, FIGO grade 1, arising in an atypical polypoid adenomyoma, precludes making a standard recommendation regarding therapy, so the decision of hysterectomy versus a nonsurgical approach should be individualized for each patient. Atypical polypoid adenomyoma usually arises in the lower uterine segment during the reproductive years or in perimenopausal women and seldom occurs in postmenopausal patients. This tumor can also arise in the uterine fundus or cervix. It is circumscribed and polypoid and ranges in size from a few millimeters to 6 cm (15,16). Patients usually present with abnormal uterine bleeding. An association with Turner syndrome has been reported in a few cases (17).
FIGURE 8.4 Atypical polypoid adenomyoma, irregularly distributed endometrioid glands surrounded by intersecting fascicles of smooth muscle.
The diagnosis of atypical polypoid adenomyoma warrants long-term follow-up for those patients opting for fertility preservation as disease persistence or local recurrence has been reported to range from 8% to 45% in these cases (15,16,18). This tumor has to be distinguished from a myoinvasive endometrial adenocarcinoma and attention to the following findings will facilitate the correct diagnosis: young age (average age 39 years) and the histologic appearance of the smooth muscle because the muscular tissue in atypical polypoid adenomyoma is more cellular than normal myometrium and is arranged in intersecting fascicles. In addition, the presence of glandular proliferation exclusively in fragments containing muscular tissue should facilitate the diagnosis because it would be unusual for a well-differentiated adenocarcinoma to be detected exclusively as a myoinvasive lesion without involvement of fragments of endometrium in the background. Recently, h-caldesmon immunostain has been proposed as a useful tool to distinguish atypical polypoid adenomyoma from myoinvasive endometrial adenocarcinoma. A study with a very limited number of cases has found that h-caldesmon stains uterine smooth muscle, whereas the myofibroblastic stroma of atypical polypoid adenomyoma lacks expression of this marker (19).
Adenosarcoma is characterized by a malignant stromal component and an epithelial component that is either normal or hyperplastic. It has been proposed that at least one of the following three criteria is sufficient for its diagnosis: (a) moderate to marked cytologic atypia of the stromal cells, (b) periglandular cuffing, and (c) a mitotic index of at least 2 mitoses per 10 HPFs in the stroma (Figs. 8.5 and 8.6, e-Figs. 8.16–8.27) (1). In our experience, however, cases of adenosarcoma have at least two of these features. The glandular component of this tumor shows variation in shape and size and is usually lined by proliferative endometrioid epithelium, although it can also be lined by endocervical, squamous, tubal, clear cell, or secretory endometrioid epithelium; reactive glandular atypia can be seen. The stroma can form papillary projections into the glandular spaces or onto the tumor surface. Cells resembling endometrial stromal cells or fibroblasts usually comprise the sarcomatous elements. Smooth muscle, sex cord–like differentiation, and heterologous elements, either benign or malignant, such as rhabdomyoblasts, fat, or cartilage, may be encountered (e-Figs. 8.28–8.32). When a pure sarcomatous component replaces at least 25% of an otherwise typical adenosarcoma, the term sarcomatous overgrowth is used (e-Figs. 8.33–8.38). In many cases, thorough sampling of the neoplasm in the hysterectomy specimen is necessary to exclude the presence of this adverse feature. Sarcomatous overgrowth is an important finding because it constitutes an indicator of aggressive behavior (20). In our experience, foci of high-grade sarcoma representing <25% of the neoplasm (e-Fig. 8.39) may also be indicative of more aggressive behavior; other authors have also made this observation (1). The significance of rhabdomyosarcoma within an adenosarcoma is controversial; some authors suggest that there is no change in the clinical behavior of the tumor (1), while others report that it is associated with more aggressive behavior (21). Adenosarcoma of the uterine body is usually seen in postmenopausal patients (age range 14 to 89 years; median 58 years), while those arising in the cervix are more common in younger patients (age range 13 to 67 years; mean 37 years). The most frequent symptom is uterine bleeding. These tumors arise most often in the endometrium of the fundus, seldom in the myometrium, and range in size from 1 to 17 cm. Tumors arising in the cervix are uncommon and range from 1.5 to 4.5 cm (22). The features listed as diagnostic for adenosarcoma allow for differentiation of this neoplasm from adenofibroma and endometrial polyp. It should be kept in mind that these features can be focal; therefore, a thorough microscopic examination is required to avoid missing an incipient adenosarcoma arising in an endometrial polyp or adenofibroma, particularly in postmenopausal patients. When the diagnosis is in doubt, the use of Ki-67 immunostain may be helpful. Adenosarcomas show a Ki-67 periglandular positive zone (cuffing) with a proliferation index of approximately 20%, compared with a proliferation index <5% in the remainder of the interglandular stroma “zonation.” In contrast, endometrial polyps show a low proliferative index (<5%) with the Ki-67 positive cells more evenly scattered throughout the stroma than in adenosarcoma, that is, there is no “zonation” (23). In cases of adenosarcoma arising in the cervix, the tumor has to be distinguished from embryonal rhabdomyosarcoma because the cambium layer seen in the latter can mimic the periglandular cuffing of adenosarcoma, and focal rhabdomyoblasts or frank rhabdomyosarcoma can be seen in adenosarcoma. Although the recognition of features typically seen in embryonal rhabdomyosarcoma, such as the presence of hypocellular and hypercellular areas and a definitive cambium layer confirmed by immunohistochemistry, can favor this diagnosis, still the most reliable finding is the absence of typical areas of adenosarcoma in embryonal rhabdomyosarcoma. The latter can require the microscopic examination of additional tissue.
FIGURE 8.5 Adenosarcoma, condensation of the stroma around irregularly shaped glands.
FIGURE 8.6 Adenosarcoma, one irregularly shaped gland, cytologic atypia of the stromal cells is detected at higher magnification.
Carcinosarcoma (Malignant Mixed Müllerian Tumor)
Carcinosarcoma (malignant mixed Müllerian tumor) has both malignant stromal and epithelial components. Usually, both of the components are high grade and the tumor has a definitive biphasic pattern (Figs. 8.7 and 8.8, e-Figs. 8.40–8.54). In some cases, the biphasic pattern is less conspicuous, and in very rare cases, the epithelial and stromal components are low grade (24). The epithelial component can be endometrioid, serous, clear cell, undifferentiated, or squamous. The latter is more commonly seen in tumors arising in the cervix. The stromal component can be either homologous (i.e., undifferentiated sarcoma, leiomyosarcoma, or endometrial stromal sarcoma) or heterologous (i.e., rhabdomyosarcoma, chondrosarcoma, osteosarcoma, and liposarcoma) (25). Carcinosarcoma is usually a disease of postmenopausal women, although cases in younger patients, including children, have been reported (26,27). In the uterine body, these tumors can be confined to a polyp or can occupy the entire endometrial cavity. In the cervix, they can range in size from 1.1 to 10 cm (28). The usual presentation is vaginal bleeding. The differential diagnosis of this neoplasm includes the following:
1.Endometrioid adenocarcinoma with focal cartilaginous or osseous metaplasia: This tumor is a FIGO grade 2 or 3 neoplasm in which the solid component has a focus of cartilaginous or osseous metaplasia without atypia or mitotic activity.
2.Endometrioid adenocarcinoma with hyalinization and sex cord–like pattern: In this variant of endometrioid adenocarcinoma, the neoplastic cells, often in a trabecular or nested arrangement, are embedded in a hyalinized or myxoid matrix that can mimic osteosarcomatous or chondrosarcomatous differentiation. This carcinoma can also have a spindled, or sarcomatoid, pattern. However, the cytologic atypia and mitotic activity in these areas are less than that expected for the sarcomatous component of a malignant mixed Müllerian tumor. In addition, the cells in these areas merge with some of the adjacent glands (29).
3.Pure sarcoma in a biopsy or curettage: In these cases, it is necessary to include a comment concerning the possibility of an undersampled carcinosarcoma (i.e., carcinomatous component missed by the biopsy).
FIGURE 8.7 Malignant mixed Müllerian tumor with heterologous cartilaginous elements.
FIGURE 8.8 Malignant mixed Müllerian tumor with homologous sarcoma.
Pure mesenchymal lesions can arise from endometrial stroma, smooth muscle, striated muscle, or other mesenchymal components such as perivascular cells, blood vessels, and adipose tissue.
Neoplasms Arising from Endometrial Stroma
ENDOMETRIAL STROMAL NODULE. Endometrial stromal nodule shares histologic features with endometrial stromal sarcoma—a proliferation of uniform oval or round cells with scanty cytoplasm growing in sheets, associated with a distinct proliferation of small arterioles that mimic the spiral arterioles of proliferative endometrium. There is a tendency for the neoplastic cells to whorl around these arterioles. Endometrial stromal nodule has a pushing margin and does not infiltrate the myometrium or invade vascular/lymphatic spaces (Figs. 8.9–8.11). In most cases, its differentiation from endometrial stromal sarcoma is not possible in an endometrial biopsy or curettage because these two parameters cannot be evaluated in a limited superficial sample (Fig. 8.12, e-Figs. 8.55 and 8.56). In these cases, the diagnosis rendered is “endometrial stromal lesion or neoplasm,” with a comment stating the need for examination of additional tissue, ideally from a hysterectomy specimen, to rule out the presence of myometrial or vascular/lymphatic invasion. An endometrial stromal nodule can be polypoid, submucosal, or intramural; is quite variable in size (from <1 to 22 cm; mean 7.1 cm); and seldom has necrosis or hemorrhage (e-Figs. 8.57 and 8.58) (30–33). The mitotic index is usually low (up to 5 mitoses per 10 HPFs) but can reach up to 24 mitoses per 10 HPFs (31), and atypical mitotic figures are absent. Endometrial stromal nodule usually has a smooth contour, although it can be ragged and extend up to 3 mm away from the main contour of the tumor into the adjacent myometrium (Fig. 8.13) (33). Some authors have proposed to adjust this 3-mm cutoff point to 6 mm and to designate the lesions with up to 6 mm of extension as endometrial stromal nodules with limited infiltration (31). We do not endorse this change or the use of this term because of the current limited experience with these cases. Other occasional features of endometrial stromal nodule, also shared by endometrial stromal sarcoma, include fibrosis, hyalinization, prominent myxoid matrix, foamy cells, edema; bands, plaques, or nodules of hyalinized collagen (sometimes with a starburst pattern); epithelioid cells with eosinophilic cytoplasm, glandular differentiation, sex cord–like differentiation; a few large thick-walled blood vessels; smooth muscle differentiation; and skeletal muscle (e-Figs. 8.59–8.65) (31–33). Immunoperoxidase studies show that the neoplastic cells are diffusely positive for CD10, either negative or focally positive for desmin, and negative for caldesmon. Tumors with smooth muscle metaplasia have a tendency to express desmin and caldesmon in the areas of smooth muscle differentiation. A rare case of endometrial stromal nodule can show up to 50% of the cells positive for desmin, but lack expression of caldesmon (34). Tumors with changes such as fibrosis or inflammation have decreased expression of CD10. Table 8.1 summarizes the pathologic features distinguishing endometrial stromal nodule, endometrial stromal sarcoma, and highly cellular leiomyoma.
FIGURE 8.9 Endometrial stromal nodule, circumscribed margin.
FIGURE 8.10 Endometrial stromal nodule, proliferation of uniform cells associated with a proliferation of arterioles; features shared with endometrial stromal sarcoma.
FIGURE 8.11 Endometrial stromal nodule, uniform oval or round cells; features shared with endometrial stromal sarcoma.
FIGURE 8.12 Detached fragment of endometrial stromal lesion, cannot evaluate the margins or the presence of vascular/lymphatic invasion.
FIGURE 8.13 Endometrial stromal nodule, focally irregular border; projection of the tumor into the adjacent myometrium can reach up to 3 mm from the border of the neoplasm.
ENDOMETRIAL STROMAL SARCOMA. As mentioned previously, endometrial stromal sarcoma shares the histologic and immunohistochemical features of endometrial stromal nodule, with the distinction that it invades the myometrium and/or vascular spaces (Figs. 8.14 and 8.15, e-Figs. 8.66–8.79). This is a neoplasm predominantly of premenopausal patients (age range 20 to 60 years; median 39 years). Abnormal uterine bleeding is the most common presentation, but occasionally this tumor is incidentally found. Grossly, it can produce diffuse thickness of the uterine wall, a single mass, or multiple masses; at times, there can be necrosis or hemorrhage. Although in the past, the mitotic index was used to designate tumors as low and high grade, this practice is now obsolete. Currently, the diagnosis of endometrial stromal sarcoma is restricted to tumors composed of monotonous, short spindle cells with an arborizing vascular pattern (i.e., resembling proliferative endometrial stroma). Tumors with these features are considered a low-grade neoplasm, regardless of the mitotic index (30,35). Tumors with high-grade nuclear features and typically no resemblance to endometrial stroma are classified as undifferentiated endometrial sarcoma (see next section). Some authors have recognized a subset of tumors that have higher grade nuclear features than endometrial stromal sarcoma yet lack the marked pleomorphism of undifferentiated endometrial sarcoma (Fig. 8.16, e-Figs. 8.80 and 8.81) (36). Morphologic distinction from both typical endometrial stromal sarcoma and undifferentiated endometrial sarcoma has gained support by the demonstration of a specific gene rearrangement (t(10;17)(q22;p13) (YWHAE-FAM22) in some tumors with these histologic features (37–39). Typical endometrial stromal sarcoma is associated with rearrangement of genes involved in chromatin binding (JAZF1, SUZ12, PHF1, and EPC1), while undifferentiated endometrial sarcoma has no recurring gene rearrangement yet identified. Furthermore, the behavior of these tumors seemed intermediate between endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Less than 50 such tumors have been well described, and the incidence of this mutation is unknown. At this time, it is premature to subdivide endometrial stromal sarcoma into low and high grades based on molecular findings. However, it is important to be aware that tumors with features intermediate between endometrial stromal sarcoma and undifferentiated sarcoma exist. Most recently, cyclin D1 has been described as an immunohistochemical surrogate marker for the YWHAE-FAM22 translocation (40). A rare phenomenon that should be kept in mind is dedifferentiation (i.e., a high-grade sarcoma arising in an endometrial stromal sarcoma) (e-Figs. 8.82 and 8.83). This can occur in the initial neoplasm, metastases, or recurrences (41–43).
FIGURE 8.14 Endometrial stromal sarcoma, diffuse infiltration into the myometrium.
FIGURE 8.15 Endometrial stromal sarcoma, vascular invasion.
FIGURE 8.16 Endometrial stromal sarcoma, YWHAE-FAM22 associated type, note the higher nuclear grade (i.e., larger nuclear size and nuclear contour irregularities) compared with JAZF1-rearranged endometrial stromal sarcoma. Note the absence of the marked nuclear pleomorphism seen in undifferentiated endometrial sarcoma (Fig. 8.17).
UNDIFFERENTIATED ENDOMETRIAL SARCOMA (POORLY DIFFERENTIATED ENDOMETRIAL SARCOMA). Undifferentiated endometrial sarcoma (poorly differentiated sarcoma) is characterized by pleomorphism of the neoplastic cells and by the absence of the distinct vascular pattern typically seen in endometrial stromal sarcoma (Fig. 8.17, e-Figs. 8.84–8.86). The cells vary from round to spindle shaped and are arranged mostly in solid sheets, although focal fascicle formation can be seen. This tumor occurs predominantly in postmenopausal patients and is very aggressive. Undifferentiated endometrial sarcoma is recognized as an endometrial sarcoma only because of its topographic relationship to the endometrium, and this is usually identified after examination of a hysterectomy specimen (35). In addition, immunostains such as keratin, epithelial membrane antigen, desmin, and CD45 are required to exclude undifferentiated carcinoma, leiomyosarcoma, or lymphoma. It is important to bear in mind that CD10 can be expressed by other high-grade sarcomas such as leiomyosarcoma, and its expression should not be equated with the diagnosis of undifferentiated endometrial sarcoma or endometrial stromal sarcoma.
MIXED ENDOMETRIAL STROMAL/SMOOTH MUSCLE TUMORS. For a mixed endometrial stromal–smooth muscle neoplasm designation, the minor component must occupy >30% of the tumor (44,45). As these mixed tumors are most similar to endometrial stromal neoplasms (e.g., in their behavior), endometrial stromal criteria and nomenclature are used for diagnosis (i.e., endometrial stromal nodule with smooth muscle metaplasia and endometrial stromal sarcoma with smooth muscle metaplasia) (Figs. 8.18 and 8.19, e-Figs. 8.87–8.91) (44,45).
FIGURE 8.17 Undifferentiated endometrial sarcoma. Note the marked pleomorphism of the neoplastic cells and the absence of a distinct small vessel proliferation.
FIGURE 8.18 Combined leiomyoma and endometrial stromal nodule, leiomyoma component.
FIGURE 8.19 Combined leiomyoma and endometrial stromal nodule, endometrial stromal nodule component.
Lesions Arising from Smooth Muscle, Usual Type
LEIOMYOMA. Leiomyoma is the most common mesenchymal neoplasm of the uterus. It is typically composed of bland spindle cells with cigar-shaped nuclei and a mitotic index of up to 4 mitoses per 10 HPFs (Fig. 8.20, e-Figs. 8.92–8.95). This tumor can have a wide variety of features as detailed in the following text.
SUBMUCOSAL LEIOMYOMA. Submucosal leiomyoma can be mistaken for an endometrial stromal lesion (Fig. 8.21, e-Figs. 8.96–8.105). It can have marked edema that can be a confusing factor; other changes include ulcerative necrosis, erosion, and thrombosis (Fig. 8.22, e-Figs. 8.106–8.109).
LEIOMYOMA WITH HYALIN NECROSIS. Hyalin necrosis, or infarct-type necrosis, refers to the presence of a necrotic area separated from the viable tumor by a hypocellular band of tissue that is usually hyalinized, although it can be just granulation tissue (Fig. 8.23, e-Figs. 8.110 and 8.111) (see Table 8.2 for comparison with other types of necrosis). Within the hyalin necrosis, blood vessels frequently have a uniformly pale “ghost” outline and hemorrhage is often seen. The cells within the necrotic areas can appear mummified and show no pleomorphism. One should be cautious in cases in which the hyalin formation is not complete, “early hyalin necrosis,” as these areas can mimic focal coagulative necrosis in a leiomyosarcoma.
FIGURE 8.20 Leiomyoma, bland spindle cells with cigar-shaped nuclei arranged in fascicles.
FIGURE 8.21 Submucosal leiomyoma, not to be mistaken for an endometrial neoplasm.
FIGURE 8.22 Submucosal leiomyoma, areas of hemorrhage and surface erosion.
FIGURE 8.23 Hyalin necrosis in leiomyoma, prominent hyalin formation and uniformity of “ghost cells.”
NEURILEMMOMA-LIKE LEIOMYOMA. In this type of leiomyoma, the nuclei are palisaded, mimicking Verocay bodies (Fig. 8.24, e-Figs. 8.112–8.114) (46).
MITOTICALLY ACTIVE LEIOMYOMA. The terms mitotically active leiomyoma and leiomyoma with increased mitotic index are used to designate typical or cellular leiomyomas with a mitotic index ranging from 5 to 19 mitoses per 10 HPFs (Fig. 8.25, e-Figs. 8.115–8.117) (47–50). This increased mitotic index is usually associated with the secretory phase of the menstrual cycle, pregnancy, or the use of exogenous progesterone (51,52). Tumors with a mitotic index of ≥20 mitoses per 10 HPFs are uncommon and experience with them is limited; therefore, they should be designated as such (i.e., leiomyoma with increased mitotic index but experience limited) (47). Mitotically active leiomyomas can have mild nuclear pleomorphism. They can be soft and fleshy with cystic or hemorrhagic areas and appear most frequently to be in a submucosal location (47,48,50). Vascular invasion within the confines of the tumor has been reported (50). In cases in which this feature is detected, or in cases with ≥20 mitoses per 10 HPFs, we recommend follow-up of the patient.
LEIOMYOMA WITH HORMONE-RELATED CHANGES. Leiomyomas in pregnant patients or those receiving progestins can grow rapidly, raising a clinical suspicion of malignancy. Microscopically, these tumors can have hemorrhage, myxoid change, edema, areas of hypercellularity (e-Fig. 8.118), mild nuclear pleomorphism, increased mitotic activity particularly in areas surrounding necrosis, increased cellularity, epithelioid morphology, apoptosis, and infarct-type necrosis (e-Fig. 8.119) (53,54). In some tumors, the infarct necrosis may be incompletely developed, and no zoning phenomenon is observed, leading to potential confusion with true coagulative tumor cell necrosis. In this situation, clinical history is helpful. A degeneration pattern is seen in up to one-third of leiomyomas from pregnant women characterized by a dusky red discoloration on gross examination, and by areas of infarction (e-Fig. 8.120), hemorrhage (e-Fig. 8.121), and hyalinization microscopically (55). The terms apoplectic leiomyoma and hemorrhagic cellular leiomyoma
