Giant cell tumors of soft tissue: a clinicopathologic study of 18 benign and malignant tumors

Primary giant cell tumors (GCTs) of soft tissue resembling osseous GCTs are uncommon but distinct entities. Malignant GCTs of soft tissue have been designated giant cell malignant fibrous histiocytomas; however, there is scant data regarding benign GCTs of soft tissue. Eleven benign and seven malignant GCTs of soft tissue were identified from the authors' consultation files and the surgical pathology files of the Vancouver General Hospital and Massachusetts General Hospital. The tumors occurred in adults (eight men, 10 women; age range, 25-89 years; mean age, 54 years) in the extremities (n = 14) and in the trunk, abdomen, and pelvis (n = 4). In each patient the skeleton was normal and there was no history of prior osseous GCT. Tumors ranged in size from 0.8 to 9.0 cm. Eleven occurred in the superficial soft tissue and seven occurred in deep soft tissue. Grossly they were circumscribed and frequently hemorrhagic. Cystic change was present in seven tumors. Nine tumors were partially surrounded by a shell of reactive bone. In all tumors, multinucleated osteoclast-like giant cells were distributed uniformly and evenly among mononuclear cells. The histologically benign GCTs of soft tissue were identical to typical osseous GCTs. The mononuclear cells in these tumors lacked nuclear atypia or pleomorphism, and the mitotic rate within this population was low (mean, three mitoses per 10 high-power fields [HPF]). In the malignant GCTs of soft tissue, the mononuclear cells exhibited anisocytosis, nuclear atypia, pleomorphism, and readily detectable mitoses including atypical forms (mean, 25 mitoses per 10 HPF). None of the benign or malignant tumors exhibited neoplastic bone production. The benign and malignant GCTs of soft tissue demonstrated a similar immunohistochemical staining profile to GCT of bone ( 12 tumors examined), exhibiting strong positive staining for CD68 within multinucleated osteoclastlike cells, and focal staining of mononuclear cells for CD68, Ham 56, and smooth muscle actin. All tumors were treated by surgical resection. Follow-up information is available for 15 patients (range, 0-108 months). No benign tumor has recurred or metastasized. Of the four patients with malignant tumors for whom follow-up information is available, one died of metastatic disease at 13 months and one developed a local recurrence at 84 months but is alive, apparently free of disease after additional excisional surgery. Primary GCTs of soft tissue are distinctive neoplasms that, like osseous GCTs, exhibit a wide clinicopathologic spectrum. These neoplasms should be distinguished from other giant cell-rich soft-tissue tumors with which they may be confused.     

Smooth muscle tumors of the ovary: a clinicopathologic study of 54 cases emphasizing prognostic criteria, histologic variants, and differential diagnosis

We studied 54 ovarian smooth muscle tumors with an emphasis on histologic criteria for malignancy. Twenty-two leiomyomas were identified, including 7 typical, 11 cellular, 2 mitotically active, 1 with bizarre nuclei, and 1 myxoid. Follow-up ranging from 12 to 240 months (mean, 77.6 months) was available for 14 patients; all were alive with no evidence of disease. Of 26 leiomyosarcomas, including 2 myxoid leiomyosarcomas, most were readily diagnosed by the presence of at least two of the following: moderate or severe cytologic atypia, mitotic rate > or =10 mitotic figures per 10 high power fields, and tumor cell necrosis. Some cytologically atypical tumors demonstrated lesser mitotic activity of 5 to 9 mitotic figures per 10 high power fields, in the absence of tumor cell necrosis. Sixty percent of these were clinically malignant, supporting a diagnosis of leiomyosarcoma in such tumors. Follow-up was available for 21 patients. Seventy-one percent developed recurrent disease at a mean of 19 months, and 62% died of their disease at a mean of 24 months. Four tumors were deemed of uncertain malignant potential, and two that were stage II both recurred in the pelvis. One case of ovarian intravenous leiomyomatosis had a benign outcome at 42 months, as did one case of ovarian leiomyoma with leiomyomatosis peritonealis disseminata at 180 months. Overall, ovarian smooth muscle tumors encompass the same varied histologic spectrum as their uterine counterparts. The main tumors in the differential diagnosis are those in the fibroma/thecoma category, spindle cell carcinomas, and metastatic gastrointestinal stromal tumors.     

Smooth muscle neoplasms of the urinary bladder: a clinicopathologic comparison of leiomyoma and leiomyosarcoma

We report the clinicopathologic, immunohistochemical, and DNA ploidy findings of 18 leiomyosarcomas of the urinary bladder. In addition, we compare these malignant smooth muscle tumors with 10 cases of urinary bladder leiomyoma. The 14 male and four female patients with leiomyosarcoma ranged in age from 25 to 88 years (mean 64 years). The tumors ranged from 3.0 to 15.0 cm (mean 7.1 cm) in greatest dimension and were moderately to highly cellular, consisting of interlacing fascicles of spindled cells with mild to marked nuclear atypia. Coagulative tumor necrosis was identified in 14 cases (78%), and mitotic activity ranged from 1 to 42 mitotic figures (MF) per 10 high power fields (HPF) (mean 12 MF/10 HPF). Tumors were classified as either high-grade (12 cases) or low-grade (six cases) based on nuclear atypia, mitotic activity, and tumor necrosis. Actin positivity was present in 15 tumors (83%), and desmin immunoreactivity was present in seven tumors (39%). All cases were negative for epithelial markers and S-100. Proliferative activity, as assessed by MIB-1 staining, ranged from 0.1% to 51.4% (median 9.1%). Seven (39%) of the leiomyosarcomas were DNA aneuploid, eight (44%) were tetraploid, and three (17%) were diploid. Five patients underwent radical cystoprostatectomy, one radical cystectomy, seven had partial cystectomy, two underwent pelvic exenteration, and three patients had transurethral resection only. Follow-up information was available on all 18 cases and ranged from 2 to 68 months (mean 22 months). Of the 12 patients with high-grade tumors, six (50%) died of disease from 2 to 20 months (mean 7 months) after diagnosis and three patients (25%) are alive with metastatic tumor. Two of the six patients with low-grade leiomyosarcoma died of tumor, 61 and 68 months after diagnosis. There were five male and five female patients with leiomyoma ranging in age from 22 to 78 years (mean 61 years). The tumors ranged from 0.5 to 4.5 cm (mean 1.6 cm) in greatest dimension, were well circumscribed, and had low cellularity. Mitotic activity, necrosis, and cellular atypia were absent, and the tumors were strongly positive for both actin and desmin. MIB-1 staining ranged from 0% to 3.8% (median 0.8%). Seven (87.5%) of the leiomyomas were DNA diploid or near-diploid and one (12.5%) was DNA aneuploid. Six patients were treated with transurethral resection and four with partial cystectomy. All 10 patients were alive at the last follow-up (mean follow-up 75 months), and no tumor recurred or metastasized. Our study shows that low-grade leiomyosarcomas are capable of malignant behavior, and high-grade leiomyosarcomas appear to behave more aggressively than low-grade tumors. In addition, the diagnosis of urinary bladder leiomyoma should be reserved for noninfiltrative smooth muscle tumors lacking mitotic activity, cytologic atypia, and necrosis.     

Fibrosarcoma-malignant fibrous histiocytoma of the breast. A clinicopathological study of 32 cases.

We report the clinical and pathologic features of 32 sarcomas of the breast with features spanning the spectrum of fibrosarcomas-malignant fibrous histiocytomas. Neoplasms were categorized as high- or low-grade lesions depending on a combination of the degrees of atypia and mitotic activity. The majority of high-grade lesions had marked (3+) nuclear atypia and at least five mitotic figures per 10 hpf. High-grade lesions with moderate (2+) nuclear atypia had a mitotic activity of six or more mitotic figures per 10 hpf. All low-grade lesions had five or fewer mitotic figures per 10 hpf, and none had a score of the nuclear grade times mitotic figures of more than 10. The average mitotic activity in low-grade lesions was two mitotic figures per 10 hpf; the high-grade lesions had 12 mitotic figures per 10 hpf. Sixty-nine percent of the low-grade fibrosarcomas-malignant fibrous histiocytomas showed mild (1+) cytologic atypia, and 69% of the high-grade lesions showed severe (3+) cytologic atypia. The herringbone pattern was associated with a more favorable prognosis than the malignant fibrous histiocytoma pattern. Compared to the high-grade lesions, low-grade fibrosarcomas-malignant fibrous histiocytomas were slow-growing, produced fewer recurrences, and did not metastasize. Of the 16 women with low-grade lesions, all were free of tumor at last contact, despite recurrence in more than half of the patients. In contrast, 31% of the patients with high-grade lesions died of tumor, and 13% were alive with disease. Twenty-five percent of women with high-grade lesions developed distant metastases.     

Sertoli cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 54 cases

Ovarian Sertoli cell tumors are rare, and their morphologic spectrum, behavior, and factors influencing the latter are not clearly established. They may be mimicked by many different tumors, some of them more frequent than Sertoli cell tumors; immunohistochemistry may aid in this differential, but its role has not been analyzed in a large series. We studied the clinicopathologic features of 54 Sertoli cell tumors, including the immunohistochemical profile of 23 of them. The patients, 6 of whom had Peutz-Jeghers syndrome, ranged from 2 to 76 years of age (mean, 30 years). Eleven patients had estrogenic and 4 had androgenic manifestations. The tumors ranged from 0.8 to 30 cm, with the majority being in the range of 4 to 12 cm. They were all unilateral, usually solid, and often yellow. The predominant microscopic pattern was tubular, seen, albeit often only focally, in all tumors; other patterns were cords or trabeculae (28), diffuse (21), pseudopapillary (4), retiform (3), islands or alveolar arrangements (3), and spindled (3). The tubules were solid or hollow with the former being somewhat more common. Delicate septa were occasionally seen and were conspicuous in areas of one tumor. The stroma was abundant in 15 tumors with marked sclerosis in 4. The cells usually had pale to occasionally densely eosinophilic cytoplasm, but 6 tumors were composed of cells with prominent foamy cytoplasm, falling in the category of "lipid-rich" Sertoli cell tumor, and one had cells with clear non-foamy cytoplasm. Forty-four tumors were stage I (42 of them were stage Ia and 2 were stage Ic), 1 was stage II, 3 were stage III, and 6 were not adequately staged. Follow-up was available for 27 patients with stage I tumors, and all were alive and well at last follow-up except for 2 patients with stage Ia and 1 with stage Ic disease. Those 3 patients had pelvic-abdominal recurrences 18, 36, and 9 months, respectively, after the initial diagnosis. Two of the three clinically malignant stage I tumors had moderate to severe cytologic atypia and brisk mitotic activity (>5 or more mitoses/10 high power fields [HPFs]), and one of these had tumor cell necrosis. Among the 10 clinically benign stage I tumors with more than 5 years of follow-up, only 3 had >5 mitoses/10 HPFs, but none had more than mild cytologic atypia and none had tumor cell necrosis. Two of the three patients with stage III disease had follow-up information and one was alive at 16 months and the second developed splenic metastases 2 years after the initial diagnosis. Two of the three stage III tumors had at least moderate cytologic atypia and brisk mitotic activity. Immunohistochemical stains showed positivity for AE1/3-Cam5.2 in 15 of 23 tumors; Epithelial membrane antigen (EMA) was negative in all the tumors. Inhibin was positive in 18 of 22 tumors, calretinin in 10 of 20, CD99 in 19 of 22, vimentin in 17 of 18, smooth muscle actin in 4 of 18, neuron specific enolase in 8 of 16, S-100 in 2 of 20, and chromogranin was negative in all 21 cases studied. Although Sertoli cell tumors usually have a distinctive tubular pattern that facilitates the diagnosis, other patterns may occasionally predominate, causing confusion with various other primary and metastatic ovarian tumors. EMA, inhibin, and chromogranin represent the most helpful triad of immunomarkers serving to exclude two common mimics of Sertoli cell tumors (endometrioid carcinoma [inhibin-; EMA+; chromogranin-] and carcinoid tumor [inhibin-; EMA+; chromogranin+]). Although CD99 and calretinin are often expressed in these tumors, they are much less specific and not as helpful in the differential diagnosis. Most Sertoli cell tumors are stage I, unilateral, cytologically bland, and clinically benign, but occasional examples are high stage, and about 11% of stage I tumors have worrisome histologic features that may portend an adverse outcome. The tumors typically occur in young females, sometimes children who typically present with sexual precocity, and occasional patients have Peutz-Jeghers syndrome.     

Do leiomyomas of deep soft tissue exist? An analysis of highly differentiated smooth muscle tumors of deep soft tissue supporting two distinct subtypes.

There is a prevailing view that leiomyomas of deep soft tissue are rare or nonexistent, but there are limited data on this subject in the form of large clinical studies with long follow-up information. We reviewed 36 consultation cases that had been diagnosed as leiomyoma or probable leiomyoma based on absence of nuclear atypia, necrosis, and no/minimal mitotic activity. Follow-up information was obtained to determine whether these stringent histologic criteria could identify a biologically benign group of smooth muscle tumors of deep soft tissue. The tumors occurred in two distinct locations. The first (n = 13) occurred in deep somatic soft tissue of the lower extremity (7), upper extremity (2), trunk (2), axilla (1), and back (1) and affected the sexes equally (7 male, 6 female). Composed of a circumscribed mass of mature smooth muscle cells, they were frequently calcified with a mean mitotic activity of <1 mitosis/50 high power fields (HPF) (range 1-4 mitoses/50 HPF). Estrogen receptor and progesterone receptor proteins were negative in the three cases tested. No tumors recurred or metastasized (mean follow-up 58.7 months, range 5-97 months). The second group (n = 23) occurred within the retroperitoneum (20) or abdominal cavity (3) of women (1 male, 22 female). Resembling uterine leiomyomas, they were always distinct from the uterus, occasionally multiple (n = 4), and sometimes occurred up to years after hysterectomy (n = 3). Four cases occurred with synchronous uterine leiomyomas. In the six cases tested, five of six were positive for the estrogen receptor protein and all were positive for progesterone receptor protein. Mean mitotic activity was 1 mitosis/50 HPF (range <1-10 mitoses/50 HPF). None developed metastasis within the follow-up period (mean 42.5 months, range 6-120 months); one tumor with a positive margin recurred at 10 months. We conclude that clinically benign smooth muscle tumors of deep soft tissue are rare but can be identified using stringent histologic criteria. They comprise two distinct subtypes: leiomyomas of somatic soft tissue and retroperitoneal-abdominal leiomyomas. The latter probably arise from hormonally sensitive smooth muscle. Although similar to uterine leiomyomas, they are located at sites removed from the uterus and are likely independent soft tissue primaries rather than parasitic leiomyomas of the uterus. We suggest that these two groups of smooth muscle tumors be diagnostically approached in a site-specific fashion.     

Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis

Intra-abdominal fibromatosis (IAF) is an uncommon benign neoplasm that usually occurs in the mesentery or retroperitoneum and may, on occasion, mimic a gastrointestinal stromal tumor (GIST). Differentiating between these two entities is important clinically because IAF is a benign tumor whereas GISTs frequently have malignant potential. In this study, the authors identified 13 cases of IAF with prominent involvement of the bowel wall as well as 35 GISTs of the small intestine, colon, or mesentery and analyzed their clinical, gross, histologic, immunophenotypic, and ultrastructural characteristics to identify important distinguishing features. Patients with IAF were younger (mean, 34 yrs) than patients with GIST (mean, 54 yrs). Both types of tumors tended to be large, but GISTs were soft and lobulated with hemorrhage, necrosis, or cystification whereas IAFs were firm, tan, and homogeneous. Histologic features characteristic of GIST included the presence of spindle or epithelioid cells with variable architecture, mitotic activity (range, <1-95 mitoses/50 high-power fields [hpf]; mean, 15 mitoses/50 hpf), nuclear atypia, and myxoid or hyalinized stroma. Necrosis and hemorrhage were seen in 16 and 25 tumors, respectively. In contrast, IAFs were composed of broad, sweeping fascicles of monotonous spindle cells with mitotic activity (range, <3-11 mitoses/50 hpf; mean, 4 mitoses/50 hpf), bland nuclear features, and finely collagenous stroma. Necrosis, hemorrhage, and myxoid degeneration were not seen. Immunohistochemical studies performed on a limited number of GISTs and IAFs demonstrated that cells expressed vimentin (100% GIST and IAF), CD117 (88% GIST and 75% IAF), CD34 (42% GIST and 0% IAF), smooth muscle actin (63% GIST and 75% IAF), muscle actin (75% GIST and 75% IAF), desmin (8% GIST and 50% IAF), and S-100 protein (16% GIST and 0% IAF). Ultrastructural analysis of 21 GISTs revealed incomplete smooth muscle differentiation in some tumors whereas IAFs were shown to have complete myofibroblastic/fibroblastic differentiation. Information regarding clinical outcome was available on 29 patients and revealed that three patients with histologically benign GISTs were alive with no evidence of disease at 5 months to 6 years (mean, 3.5 yrs) and one patient with a histologically benign tumor died of disease after 7 years. Of patients with histologically malignant GIST, one died of surgical complications, 10 were alive without disease at I to 13 years (mean, 5.4 yrs), four were alive with disease at 4 months to 15 years (mean, 3.8 yrs), three had disseminated disease at operation, and seven were dead of disease at 10 months to 3 years (mean, 2.2 yrs). Follow up of eight patients with IAF demonstrated that five were alive without disease at 4 months to 15 years (mean, 5.3 yrs) and three had recurrences at 1 (two patients) and 2 years (one patient). In summary, IAFs can have many features (large size, infiltration of adjacent structures, mitotic activity) that can cause diagnostic confusion with GISTs and, importantly, the degree of mitotic activity present in IAFs may overlap that seen in malignant GISTs. These entities can be distinguished primarily by their light microscopic and ultrastructural features but there is a notable overlap in their immunohistochemical profiles. The distinction between these neoplasms is important because there are important clinical implications for the patient.     

Retroperitoneal leiomyomas: a clinicopathologic and immunohistochemical study of 56 cases with a comparison to retroperitoneal leiomyosarcomas.

Most retroperitoneal smooth muscle tumors are believed to be malignant, and leiomyomas are considered very rare. This study was undertaken to determine the clinicopathologic features and long-term follow-up of 56 tumors diagnosed as retroperitoneal leiomyomas (LM) or smooth muscle tumors with an uncertain malignant potential (SMTUMP) in an effort to correlate their behavior and clinicopathologic features. These tumors were compared with a series of 11 cases of retroperitoneal leiomyosarcomas (excluding gastrointestinal stromal tumors). Histologic slides and immunohistochemistry for SMA, desmin, S-100 protein, HMB45, CD34, C-KIT, estrogen (ER) and progesterone (PR) receptor proteins, and MIB-1 were analyzed. All tumors diagnosed as LM and all but one SMTUMP were well-differentiated smooth muscle tumors that lacked atypia and coagulative necrosis. There was <1 mitosis per 50 high power field (HPF) in 38 tumors; no tumor had >3 mitoses/50 HPF. Most tumors had a striking resemblance to uterine smooth muscle tumors with common hyaline change and trabecular patterns. There were 51 females and 5 males ranging in age from 25 to 79 years (mean 45 years, median 43 years). These tumors were typically large, with a mean size of 16.2 cm and weight of 1600 g. Immunohistochemically, all 35 tumors studied were positive for alpha-SMA, 30 of 35 tumors were positive for desmin, and all were negative for CD117, S100 protein, and HMB45 and all but one for CD34. Steroid receptors were commonly present: ER in 20 of 29 cases and PR in 26 of 31 cases in the tumors of female patients. MIB-1 score was <2% in all of 28 cases. Long-term follow-up (mean 140 months) did not reveal metastases, but two patients had local recurrence; however, neither patient with recurrence demonstrated disease progression in follow-up. By contrast, all 11 leiomyosarcomas had at least mild atypia, and all were ER and PR negative. All cases had MIB-1-positive nuclei, but only four had >10% nuclei positive. Four patients died of disease, four were alive with recurrence, and three had no evidence of disease. A group of benign leiomyomas can be identified among retroperitoneal smooth muscle tumors. Most of these tumors resemble uterine leiomyomas by histology and positive hormone receptors, and they seem to have a good long-term prognosis with a small potential for local recurrence.     

Pleomorphic fibroma of the skin: a benign neoplasm with cytologic atypia. A clinicopathologic study of eight cases

A clinicopathologic study of eight examples of polypoid and dome-shaped cutaneous fibrous lesions with sparse cellularity but striking nuclear atypia and rare mitotic figures is presented. Positive immunohistochemical staining for vimentin and actin supported the fibroblastic nature of these lesions. All eight cases were adults whose ages ranged from 33 to 67 years (mean 52 years). Five were women and three were men. Five lesions were located on extremities, two on the trunk, and one on the face and they measured from 4 to 16 mm in greatest dimension. The lesions were clinically followed from 4 months to 5 years. They all showed benign clinical behavior, with only one local recurrence in a lesion that had been incompletely removed. The nuclear atypia seen in these fibrous lesions may be similar to that which occurs in other benign mesenchymal neoplasms, such as pleomorphic lipoma, pleomorphic leiomyoma, ancient schwannoma, and variants of dermatofibroma with atypical cells. We suggest that "pleomorphic fibroma" is an appropriate term for this lesion based on its histologic differentiation, cytologic atypia, and benign clinical course.     

Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases

We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors.     

Cutaneous Leiomyoma with Cytologic Atypia, Akin to Uterine Symplastic Leiomyoma

BACKGROUND: Smooth muscle tumors of the skin with cytologic pleomorphism and mitotic activity have traditionally been characterized as leiomyosarcomas, despite having a benign clinical course. In the uterus, there is a smooth muscle tumor known as symplastic leiomyoma, which typically has cytologic pleomorphism without significant mitotic activity. OBJECTIVE: The objective was to illustrate by case report the unusual histologic variant of the cutaneous pilar leiomyoma analogous to the symplastic leiomyoma of the uterus. METHODS: A 54-year-old woman presented with a clinical picture of cutaneous leiomyoma but had histologic features of nuclear hyperchromasia and pleomorphism, but rare mitoses. RESULTS: Management of this patient included excision of the involved area. CONCLUSION: Symplastic leiomyoma is an atypical uterine leiomyoma with cytologic atypia. We present the case of a patient with cutaneous leiomyomas that histologically demonstrated similar features to a uterine symplastic leiomyoma. We believe that this represents a distinct histologic variant of the cutaneous pilar leiomyoma analogous to the symplastic leiomyoma of the uterus.     

Pulmonary and mediastinal glomus tumors--report of five cases including a pulmonary glomangiosarcoma: a clinicopathologic study with literature review

Pulmonary and mediastinal glomus tumors are rare lesions, with four previously reported primary pulmonary cases and three mediastinal cases. The authors report one mediastinal glomus tumor, a locally infiltrative type, and four pulmonary glomus tumors, including the first case of primary pulmonary glomangiosarcoma. These tumors show a variety of clinical and pathologic differences from the more common cutaneous variety, including later age at presentation, larger size, and more frequent atypical/malignant features. Mediastinal and pulmonary glomus tumors both have an average patient age at presentation of 45 years. However, compared with their pulmonary counterparts, mediastinal glomus tumors are less common, more often symptomatic, and are larger (average size, 5.4 cm). Additionally, mediastinal glomus tumors more often demonstrate malignant or atypical features. Pulmonary glomus tumors average 3.3 cm in greatest dimension, with the majority measuring less than 2.5 cm. The pulmonary glomangiosarcoma presented was large, measuring 9.5 cm, and showed increased mitotic count (9 mitoses/10 high-power fields), necrosis, cytologic atypia, and was associated with disseminated disease. Regardless of clinical symptoms, histologic features, and even metastases, the vast majority of all benign and malignant glomus tumors are indolent and cured surgically, with adjuvant therapy needed only for occasional patients with more advanced disease. The four patients with glomus tumors reported are currently alive and free of disease as of last follow up. The patient with the glomangiosarcoma developed widespread metastases and died of disease 68 weeks after initial therapy.     

Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors

Inflammatory myofibroblastic tumor (IMT) is an indolent spindle cell proliferation that can histologically resemble various malignant mesenchymal neoplasms; however, it generally behaves as a benign or locally recurrent tumor. Most IMTs involve the lung, mesentery, omentum, or retroperitoneum. We report the clinical and pathologic features of six IMTs of the uterus, one of which was included in a previous report, and emphasize the histologic and immunohistochemical features that distinguish IMTs from uterine spindle cell neoplasms that require aggressive treatment. Recently, translocations of the anaplastic lymphoma kinase (ALK) gene and immunohistochemical expression of ALK have been reported in IMTs of various anatomic sites. We compared ALK expression in uterine IMTs with that in uterine mesenchymal neoplasms with which it may be confused. Patients with IMT were between 6 and 46 years of age. None had a history of abdominal surgery; three were multiparous. The IMTs ranged from 1 to 12 cm in maximum dimension. Three grew as polypoid masses that arose in the lower uterine segment, and two of these prolapsed through the cervical os. The three other tumors grew as bulky myometrial masses with focally irregular borders and infiltrated the endometrium, parametrium, or cervical stroma. There were three main microscopic patterns: a hypocellular pattern, a fascicular pattern, and a hyalinized pattern. A lymphoplasmacytic infiltrate was present in all of the tumors, and most had a myxoid background. Mitotic activity ranged from 0 to 2 mitotic figures per 10 high power fields (HPF) except in one tumor that focally had up to 8 mitotic figures per 10 HPF. No nuclear atypia or necrosis was present. Immunohistochemical expression of ALK was present in a cytoplasmic pattern in all IMTs tested. No ALK expression was identified in uterine leiomyoma (n = 7), leiomyosarcoma (n = 6), carcinosarcoma (n = 4), endometrial stromal sarcoma (n = 4), or normal uterine tissues. Follow-up ranging from 1.5 years to 5 years in 4 patients with uterine IMTs revealed no recurrence or metastasis. IMTs should be differentiated from aggressive uterine mesenchymal tumors because they can be treated conservatively and have a more favorable prognosis. ALK expression appears to be of diagnostic value in conjunction with other immunohistochemical stains.     

Inguinal smooth muscle tumors in women-a dichotomous group consisting of Müllerian-type leiomyomas and soft tissue leiomyosarcomas: an analysis of 55 cases

Assessment of the biological potential of smooth muscle tumors can be difficult and depends primarily on tumor site, stage, and histologic parameters. In this study, we examined the clinicopathologic and immunohistochemical features of 55 noncutaneous inguinal smooth muscle tumors of women (age range, 20 to 82 y; median, 57 y). Histologically, 23 tumors were considered as leiomyomas. They showed low mitotic activity (range, 0 to 6 mitoses/10 high-power fields, without atypical mitotic figures), minimal cytologic atypia, and absence of coagulative necrosis. Fifteen of these tumors histologically resembled conventional uterine leiomyomas and 8 resembled their variants: lipoleiomyomas (n = 2) and epithelioid variants (n = 6). The mean size was 7.8 cm, and half of the tumors with specified location arose in association with the round ligament. Immunohistochemical expression of estrogen receptor (ER) and/or Wilms tumor protein (WT1) was detected in most cases (83%), supporting Müllerian derivation. Follow-up data (range, 10 to 29 y; median, 13 y) on 11 patients showed that all were alive without disease or death from unrelated causes. The second group, classified as leiomyosarcomas, consisted of 32 mitotically active smooth muscle tumors, almost invariably with atypical mitotic figures, and exhibiting significant cytologic atypia. These patients were older than those with leiomyomas, and their tumors were mostly subcutaneous with a mean tumor size of 5.4 cm. Two leiomyosarcomas showed a femoral vein origin, but none were associated with the round ligament. All but 3 leiomyosarcomas were negative for ER. Follow-up data on 13 patients (range, 2 mo to 30 y; median, 4.5 y) showed that 5 died of metastatic sarcoma. Six individuals were alive without disease (median, 16 y), and 2 died of unrelated causes. In conclusion, inguinal smooth muscle tumors in women are a dichotomous group. They consist of ER/WT1-positive Müllerian-type leiomyomas resembling uterine leiomyomas with an excellent prognosis and conventional LMSs that are usually ER/WT1-negative and show a variable malignant course. Separation of these 2 categories is important for prognostication and optimal patient management, and is aided by immunohistochemical studies for ER and WT1.     

The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas

BACKGROUND: The most relevant factor in the progression-free survival (PFS) of patients with meningiomas is the malignant grade. However, using only the current World Health Organization (WHO) definition that does not consider precise quantitative indicators, an unequivocal diagnosis of the malignant grade is difficult. In our retrospective study of the PFS of meningioma patients, we focused on mitoses and the Ki-67 staining index of tumor specimens obtained at the initial surgery. METHODS AND RESULTS: A total of 349 patients with intracranial meningioma, operated between 1978 and 2000, were followed for a mean of 7 years. According to the mitotic index (MI), we classified them into 3 groups. In Group A (n = 326), slide-mounted tumor samples exhibited no mitoses; in Group B (n = 15) there were fewer than 4 mitoses, and in Group C (n = 8) 4 or more mitoses were seen per 10 high-power fields (HPF). The estimated 5-year PFS rates in Groups A, B, and C were 93%, 10%, and 13% respectively. The mean PFS for Group A was 148 months; in Groups B and C the median PFS was 43 and 16 months, respectively. A Ki-67 staining index (SI) of less than 1% corresponded with no mitosis, while an SI exceeding 5% was indicative of the presence of mitoses. CONCLUSION: In meningioma patients, no mitoses and/or a Ki-67 SI <1% signals a favorable outcome. An SI >5% or the presence of mitoses, even fewer than 4 in 10 HPF, is suggestive of a short PFS irrespective of other pathologic features. We suggest that in combination, assay of the Ki-67 SI and the MI represents a reliable, quantitative tool for predicting PFS in meningioma patients.     

Histopathologic prognostic factors in stage I leiomyosarcoma of the uterus: a detailed analysis of 27 cases

Uterine leiomyosarcomas (Ut-LMSs) are aggressive tumors with an overall poor prognosis (15% to 25% 5-year survival rate). However, patients with stage I Ut-LMSs are reported to have a relatively better outcome when compared with the overall group with a 5-year survival rate ranging from 25% to 75%. The purpose of this study was to evaluate the histopathologic parameters that may impact outcome in stage I Ut-LMSs. Twenty-seven patients with stage I Ut-LMSs were identified from the files of 5 tertiary care hospitals between 1974 and 2006. Tumors were primarily staged based on pathologic information, supplemented with radiologic findings (10 cases) and clinical records (1 case). Patients with stage I tumors with no additional clinical or radiologic staging information were included in the study if no recurrence was documented after 6 months from the initial staging operation (16 cases). Clinicopathologic parameters that were statistically evaluated included age [mean, 54 y (37 to 73)], tumor size [mean, 9.5 cm (5.5 to 16)], cell type (17 spindled, 5 epithelioid, 2 myxoid, and 3 mixed), mitotic activity [mean count, 24 (4 to 69)/10 high-power fields], marked cytologic atypia (26 of 27 cases), tumor cell necrosis (12 of 27 cases), and lymphovascular invasion (6 of 27 cases). Follow-up was available for all the patients. Poor outcome was defined when patients either died of disease or were alive with disease. Overall, accounting for any length of follow-up, 16 of 27 (59%) patients with stage I Ut-LMSs had poor outcome; 7 died of disease (mean follow-up, 13 mo) and 9 were alive with disease (mean follow-up, 31 mo). The remaining 11 patients were alive and well with a mean follow-up of 48 months. However, at 2 years of follow-up by univariate analysis, only nonspindle morphology (P<0.0183) and diffuse high-grade cytologic atypia (P<0.02) were statistically associated with poor outcome. No statistically significant association with survival was identified by univariate analysis when evaluating mean age, mean tumor size, presence of tumor cell necrosis, mean mitotic count, or lymphovascular invasion. In conclusion, stage I leiomyosarcoma is associated with poor prognosis. No conclusive differences were observed among different clinicopathologic parameters and prognosis, although it seemed that spindle cell morphology and diffuse high-grade cytologic atypia were associated with longer overall survival and higher death rates, respectively.     

Sertoli cell tumor of the testis

Sertoli cell tumors (TCS) derivated from sex-cord estroma cells, are an uncommon variety of testicles neoplasms. A 66 year-old patient that came to the consultation for an increased scrotum of size present. Ultrasound viewed a hipoecoic nodule capable with testicular tumor, more secondary hidrocele. After undergoing the standard treatment, by means of groin radical orchiectomy, its pathologic analysis identified the lesion as Sertoli cell tumor conventional. The pathologic features that best correlate with a clinically benign course are as follows: a lower size tumor to 5 cm, mild nuclear atypia, a mitotic rate of less than 5 mitosis per 10 high power fields, and absent necrosis. Our case presented with these features. Follow-up of these neoplasms should be prolonged by the unusual of its presentation and a small percentage of cases are clinically malignant.     

Mullerian adenosarcoma: a clinicopathologic and immunohistochemical study of 55 cases challenging the existence of adenofibroma

Mullerian adenosarcomas are rare mixed tumors of low malignant potential that occur mainly in the uterus and also in extrauterine locations. Microscopically, they may be difficult to distinguish from adenofibromas. In this clinicopathologic study of 55 adenosarcomas, the mean patient age was 50 years (range: 13 to 83 y). Thirty-seven tumors were of the uterine corpus, 11 of the cervix, 4 of the ovary, and 1 each of the fallopian tube, vagina, and Douglas peritoneum. Abdominal pain and vaginal bleeding were the usual complaints. Treatment was known in 50 patients: 10 had polypectomy, 1 cone biopsy, and 39 hysterectomy, which was accompanied by bilateral salpingo-oophorectomy in 24 and lymphadenectomy in 4. Five patients had radiotherapy and 2 of them had chemotherapy. Stage was known in 41 cases. Of 30 tumors of the uterine corpus, 17 were stage IA, 11 stage IB, 1 stage IC, and 1 stage IIIC. Four cervical tumors were stage IB. Three of the 4 ovarian tumors were stage IA and the other was stage IIIC. The tumor of the fallopian tube was stage IC, and the tumors of the vagina and recto-uterine pouch were confined to their site of origin. Most uterine tumors were polypoid masses ranging from 1 to 20 cm (mean: 6.5 cm). Microscopically, sarcomatous overgrowth was found in 18 cases (33%), heterologous elements in 13 (24%), and sex cordlike differentiation in 7 (13%). Fourteen of 30 uterine tumors (47%) had myometrial invasion that was minimal in 5, involved one-third of the myometrial thickness in 7, and more than 50% in 2. Of 4 cervical tumors, 2 were endocervical polyps, 1 invaded one-third of the cervical wall, and the other invaded its full thickness. Follow-up information (2 mo to 18 y; average: 7.5 y) was available in 29 patients. Six developed metastases and 5 of them died of tumor. Four had adenosarcomas with sarcomatous overgrowth; however, the other 2 patients had typical low-grade adenosarcomas of the uterine corpus and cervix, respectively, exhibiting only mild nuclear atypia of the stromal component and 相似文献   

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients

Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.