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.     

Transitional cell carcinoma of the ovary: a morphologic study of 100 cases with emphasis on differential diagnosis

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer, and studies of its morphology are few. As a result, the criteria for its diagnosis and spectrum of its morphology are not clearly established. One hundred consecutive consultation cases of ovarian carcinoma with a pure or partial transitional cell pattern (excluding malignant Brenner tumor) diagnosed between 1989 and 2001 were evaluated for the frequency of various pathologic features and the relation of TCC to other surface epithelial-stromal carcinomas. The women were 33 to 94 years of age (mean, 56 years). A total of 47 tumors were stage I, 21 stage II, 31 stage III, and 1 stage IV; 13% of the stage I tumors and 41% of tumors of all stages were bilateral. The tumors ranged from 3.0 to 30 cm in greatest dimension (mean, 10 cm); 60% of them were solid and cystic, 24% solid, and 16% cystic. TCC was the exclusive or predominant component in 93% of the tumors and showed undulating (93%), diffuse (57%), insular (55%), and trabecular (43%) patterns. In four tumors with an insular growth, the pattern focally mimicked a Brenner tumor. Necrosis was present in 57% of the cases. Features that were seen in the tumors that in aggregate produced a relatively consistent appearance were "punched out" microspaces (87%), often the size of Call-Exner bodies, large cystic spaces (73%), and large blunt papillae (63%). Features that were sometimes seen, usually as a focal finding, included slit-like fenestrations (49%), bizarre giant cells (35%), small filiform papillae (18%), gland-like tubules (17%), squamous differentiation (13%), and psammoma bodies (4%). In 23 cases, TCC was a component of a mixed epithelial carcinoma, the additional components being serous adenocarcinoma in 16, endometrioid in 5, mucinous in 1, and clear cell carcinoma in 1. The tumor cells of the TCC component often were relatively monomorphic; 6% of the tumors were grade 1, 43% grade 2, and 51% grade 3. The nuclei were oblong or round and often had large single nucleoli (69%) or longitudinal grooves (48%). The cytoplasm was typically pale and granular but was rarely strikingly clear or oxyphilic. TCC of the ovary usually occurs in pure form but is also common as a component of a surface epithelial carcinoma of mixed cell type. In either situation, TCC has a constellation of architectural and cytologic features that readily distinguish it in most cases from other types of ovarian cancer. Recognition of these features will lead to a more consistent diagnosis of this tumor and aid in determining whether it has distinctive clinical features, particularly with regard to its behavior.     

The morphologic spectrum of hibernoma: a clinicopathologic study of 170 cases

Hibernoma, an uncommon tumor of brown fat, has been described only in a few case reports and small series. The authors reviewed 170 cases of hibernoma and evaluated the morphologic features and the behavior of this tumor. The records from the Soft Tissue Registry of the Armed Forces Institute of Pathology from 1970 were searched for cases coded as "hibernoma." Clinical information and available slides from 170 hibernomas were reviewed. Immunohistochemical staining for S-100 and CD34 was performed on select cases. Follow-up information was obtained from the patients' medical records, the patients' physicians, and the patients themselves. Of 170 patients with hibernoma, 99 were men and 71 were women. The tumor occurred most commonly in adults, with a mean age of 38.0 years (age range, 2-75 years). Nine tumors occurred in pediatric patients. The most common anatomic locations included the thigh (n = 50), shoulder (n = 20), back (n = 17), neck (n = 16), chest (n = 11), arm (n = 11), and abdominal cavity/retroperitoneum (n = 10). The average duration of the tumor was 30.6 months. Tumor size ranged from 1 to 24 cm with an average dimension of 9.3 cm. All tumors were composed partly or principally of coarsely multivacuolated fat cells with small, central nuclei and no atypia. Four morphologic variants of hibernoma were identified: typical, myxoid, spindle cell, and lipoma-like. "Typical" hibernoma (n = 140) included eosinophilic cell, pale cell, and mixed cell types based on the tinctorial quality of the hibernoma cells. The myxoid variant (n = 14) contained a loose basophilic matrix. Spindle cell hibernoma (n = 4) had features of spindle cell lipoma and hibernoma; all occurred in the neck or scalp. The lipoma-like variant (n = 12) contained only scattered hibernoma cells. Immunohistochemically, 17 of 20 cases (85%) were positive for S-100 protein. Only one hibernoma of 20, a spindle cell variant, was positive for CD34, whereas other hibernoma variants were negative. Follow-up was obtained for 66 cases (39%) over a mean period of 7.7 years (range, 6 months-28 years). None of the patients with follow-up had a recurrence or metastasis, including eight with intramuscular tumors. No patient died of disease. Hibernoma is a tumor found most often in adults and most commonly in the thigh, with several morphologic variants. It is a benign tumor that does not recur with complete excision. Hibernomas should not be confused with atypical lipomas or well-differentiated liposarcoma.     

Low-grade serous carcinoma of the ovary metastatic to the anterior mediastinum simulating multilocular thymic cysts: a clinicopathologic and immunohistochemical study of 3 cases

Three cases of serous borderline tumors of the ovary with areas of serous low-grade carcinoma metastatic to the anterior mediastinum simulating multilocular thymic cysts are presented. The patients are women between the ages of 33 and 50 years. The 3 women had a prior history of primary ovarian neoplasms diagnosed over a period ranging from 3 to 20 years; the 3 patients were in stages IIIA, IIIB, and III. Follow-up radiologic examination revealed the presence of an anterior mediastinal tumor. The 3 patients underwent surgical resection of the mediastinal tumor. Grossly, the mediastinal tumors measured from 7 to 9 cm in greatest diameter and were described as cystic with solid areas. Focal areas of hemorrhage were present, but frank necrosis was not identified. Histologically, all the tumors basically showed similar histopathologic features, namely, those described in multilocular thymic cysts, ie, cystic structures lined by either squamous or low cuboidal epithelium, lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue. In addition, within the cystic structures, there was a neoplastic cellular proliferation with papillary architecture, nuclear atypia, and scattered mitotic figures. Immunohistochemical studies for keratin, MOC31, and CA-125 showed positive staining in tumor cells while placental-like alkaline phosphatase was negative. Two patients remain alive and well after follow-up ranging from 6 to 18 months and 1 patient died of tumor 18 years after initial diagnosis.     

Anaplastic carcinoma in mucinous ovarian tumors: a clinicopathologic study of 34 cases emphasizing the crucial impact of stage on prognosis, their histologic spectrum, and overlap with sarcomalike mural nodules

Several types of mural nodules may develop in the wall of mucinous tumors of the ovary. The histopathologic features and prognosis of foci/nodules of anaplastic carcinoma are not well known. Although they were first thought to carry an invariably unfavorable prognosis, recent data indicate that this does not necessarily apply to stage Ia tumors. Slides from 34 consultation cases of mucinous ovarian tumors with foci/nodules of anaplastic carcinoma were reviewed and classified on the basis of their morphologic features. Cytokeratin stains were done in selected cases. Staging, treatment, and follow-up information were obtained. The foci/nodules of anaplastic carcinoma were classified histologically into 3 groups: (a) rhabdoid (n=12) having a diffuse arrangement of cells with large, bright, eosinophilic cytoplasms, eccentric nuclei, and one or more prominent nucleoli; (b) sarcomatoid (n=10) characterized by a spindle cell proliferation, with atypical and vesicular nuclei often with herringbone pattern; and (c) pleomorphic (n=12) exhibiting overlapping features of the first 2 categories. International Federation of Gynecology and Obstetrics (FIGO) stage was available in 31 cases: 15 were stage Ia, 6 stage Ic, 2 stage II, 7 stage III, and 1 stage IV. Follow-up was obtained in 21 cases. Seven patients died of the disease after a median time of 8 months: 3 stage IC, 1 stage II, 1 stage III, 1 stage IV, and the other was unstaged. Ten patients were alive and clinically free of disease after a median follow-up of 5 years: they were all stage Ia. Three patients (2 stages III and 1 stage IV) were alive with disease at 3 years, 9 months, and 7 months. The other patient (stage Ia) died of an unrelated cause. Thus, only 1 patient with stage Ia disease died, and she died of causes other than ovarian cancer. The presence of foci/nodules of anaplastic carcinoma in unruptured stage I mucinous tumors of the ovary does not necessarily carry an adverse prognosis. These foci/nodules may exhibit rhabdoid, sarcomatoid (spindle cell), or pleomorphic features.     

Malignant melanoma metastatic to the ovary. A clinicopathologic analysis of 20 cases

Twenty cases of malignant melanoma metastatic to the ovary are reported. The patients, whose ages ranged from 21 to 60 (average 37.5) years, typically presented because of abdominal swelling or pain. Approximately 50% of the patients also had metastatic tumor outside the ovary, usually within the pelvis and upper abdomen, at the time of presentation. Twelve patients were known to have had a cutaneous malignant melanoma 1 month to 13 years before their ovarian tumors were discovered, and pigmented lesions had been removed previously from three other patients. Most patients are known to have died within a few years of discovery of their ovarian tumors but two were alive without evidence of disease 5 and 8 years later. The ovarian tumors, which were bilateral in nine cases, ranged up to 20 (average 10.5 cm) in greatest dimension. Six of them were either entirely black or had discernible black or brown foci. The most common microscopic appearance was that of large cells with abundant eosinophilic cytoplasm growing in nodular aggregates or diffusely. Occasional tumors were characterized by small cells with scanty cytoplasm, and in five tumors spindle cells were present. Another pattern was growth in the form of discrete rounded aggregates having a nevoid appearance. Eight tumors contained folliclelike spaces. Major cytologic features of the tumors included prominent nucleoli in 13, cytoplasmic pseudoinclusions in many nuclei in five, and intracytoplasmic melanin pigment in nine cases. In the 10 cases studied immunohistochemically, most of the tumor cells were strongly positive for S-100 protein and fewer cells were positive for HMB-45 in the seven tumors that were stained for this antigen. Melanosomes were identified in the three tumors examined ultrastructurally. These neoplasms often were difficult to differentiate from many other types of tumors, including juvenile granulosa cell tumor and small cell carcinoma, because of the presence of folliclelike spaces.     

Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4 cases

We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in 1 case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal alpha-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration.     

Malignant melanoma involving the ovary: a clinicopathologic and immunohistochemical study of 23 cases

Ovarian malignant melanoma (MM), primary or metastatic, is an extremely rare tumor and in the absence of a previous diagnosis can represent a diagnostic challenge. We present the clinicopathologic and immunohistochemical features of 23 cases seen in our institution over a period of 40 years (1962-2001). The patients' age ranged from 14 to 53 years (mean 35.7 years). Ethnicity was known in 19 patients: 14 white, 4 Hispanic, and 1 black. A previous history of MM was definitively obtained in 14 patients; in these cases, the interval between the primary MM and the ovarian metastasis ranged from 15 to 228 months (mean 77.7 months). The tumor was unilateral in 19 and bilateral in 4 cases. The tumor size ranged from 4.5 to 23 cm (average 10 cm); the melanoma arising in a cystic teratoma was 0.2 mm in thickness. The tumor was grossly pigmented in 8 cases (35%). The architectural pattern was nodular (8 cases), diffuse (6 cases), nodular and diffuse (5 cases), nested (3 cases), and lentiginous arising in a teratoma (1 case). Follicle-like spaces were seen in 8 cases, pseudo-glandular areas in 1 case, pseudo-myxoid areas in 1 case, and cords in 1 case. The tumor cell type was epithelioid in 19 cases, spindled in 2 cases, mixed epithelioid and spindled in 1 case, and small cell in 1 case. Nucleoli were prominent in 18 cases, and nuclear inclusions were present but rare in the majority of cases. Nuclear grooves were seen in 3 cases. Necrosis was extensive in 8 cases, focal in 10 cases, and was absent in 5 cases. In 8 cases, initial diagnoses included sex cord stromal tumor, germ cell tumor, sarcoma, or undifferentiated carcinoma. S-100 was positive in 18 of 19 cases, HMB-45 in 17 of 20 cases, MART-1 in 13 of 15 cases, tyrosinase in 10 of 15 cases, and Mitf in 8 of 14 cases. Inhibin was positive in 3 of 14 cases. Calretinin was focally positive in 1 of 12 cases. Treatment performed in 18 of the cases are as follows: oophorectomy with/without chemotherapy (10); total abdominal hysterectomy with bilateral salpingo-oophorectomy with/without chemotherapy (6); vaginal hysterectomy, bilateral salpingo-oophorectomy, and chemotherapy (1); and total abdominal hysterectomy with salpingo-oophorectomy (1). Follow-up ranging from 2 to 96 months was available in 18 patients. All but one had metastases in other organs, most often in the lungs. Thirteen patients died of disease (range 2-76 months), 3 are alive with disease (6-18 months), and 2 have no evidence of disease at 24 and 96 months; one was the patient with melanoma arising within a teratoma. In conclusion, MM involving the ovary is a rare disease, predominantly seen in women of reproductive age, and is associated with a poor prognosis. The tumor is most often metastatic from another site and is unilateral in most cases. Nodular or diffuse pattern and epithelioid cell type are most frequently seen, and the tumor can be mistaken for germ cell and sex cord stromal tumors. S-100 is the most sensitive marker. MART-1 was positive in the few cases that were negative with HMB-45. Inhibin can be focally positive in some cases.     

Cellular fibromas of the ovary: a study of 75 cases including 40 mitotically active tumors emphasizing their distinction from fibrosarcoma

Cellular fibroblastic tumors of the ovary are currently classified as either cellular fibroma (CF) or fibrosarcoma. The former are characterized by bland nuclei, 3 or fewer mitotic figures per 10 high-power fields (MFs/10 HPFs), and a low malignant potential, whereas fibrosarcomas usually have severe nuclear atypia, > or = 4 MFs/10 HPFs, and an aggressive clinical course. The prognosis of cellular fibromatous tumors with > or = 4 MFs/10 HPFs and low-grade cytology is not established and it is the purpose of this study to investigate that aspect. It has been our anecdotal experience that otherwise typical CFs with > or = 4 MFs/10 HPFs usually have a benign clinical course, suggesting that such tumors should be regarded as "mitotically active cellular fibroma" (MACF) rather than fibrosarcoma. Seventy-five cellular fibromatous neoplasms were analyzed to determine their clinicopathologic features and the appropriateness of "MACF" as a designation for otherwise typical CFs with > or = 4 MFs/10 HPFs. The mean age of patients with CF (n = 35, 0 to 3 MFs/10 HPFs) and MACF (n = 40, > or = 4 MFs/10 HPFs) was 51 and 41 years, respectively. Patients most commonly presented with symptoms related to a pelvic mass. All tumors were unilateral. The mean tumor size of CFs was 8.0 cm and 9.4 cm for MACFs. The majority of the tumors were solid; approximately one-third of them had a cystic component. Ovarian surface adhesions, involvement of the ovarian surface, or both, was present in 6% of CFs and 10% of MACFs. Eleven percent of CFs and 13% of MACFs were associated with extraovarian involvement. All tumors consisted of cellular, intersecting bundles of spindle cells with bland nuclear features. The mean highest mitotic count for MACFs was 6.7 MFs/10 HPFs (range 4 to 19 MFs/10 HPFs). Follow-up of 3 months to 12 years (mean 4.75 y) was available in 18 of the 40 patients with MACFs and was uneventful in all cases. We conclude that cellular fibromatous neoplasms with bland cytology and elevated mitotic counts are associated with favorable patient outcome and should be diagnosed as MACF rather than fibrosarcoma, which usually have moderate to severe atypia and elevated mitotic rates. As prior observations have shown that even typical CFs can occasionally recur locally, particularly if they are associated with rupture or adherence, long-term follow-up for patients with CFs and MACFs is appropriate.     

Granulosa cell tumors of the ovary with a pseudopapillary pattern: a study of 14 cases of an unusual morphologic variant emphasizing their distinction from transitional cell neoplasms and other papillary ovarian tumors

Granulosa cell tumors of the ovary with a pseudopapillary pattern have received only passing mention in the literature. We have reviewed the clinicopathologic features of 10 cases of juvenile granulosa cell tumor and 4 cases of adult granulosa cell tumor with a pseudopapillary pattern. Twelve cases were received in consultation; the referring pathologist favored a diagnosis of a transitional cell neoplasm in 3 of these cases, and a retiform Sertoli-Leydig cell tumor in 2 cases; in most of the remainder, the diagnosis of granulosa cell tumor was considered but uncertainty expressed because of the unusual papillarylike pattern. All 14 tumors were unilateral, and the majority were predominantly cystic, 3 unilocular, and 6 multilocular. Multiple papillary projections lining the cyst wall were noted grossly in 10 cases; these ranged in size from 0.1 to 1.5 cm and were typically soft, edematous, fleshy, or rubbery. Microscopically, pseudopapillae were formed by intracystic cellular projections with surrounding necrotic debris and/or undulating folds of neoplastic cells in the absence of appreciable necrosis. In all tumors, thorough sampling revealed areas with architectural patterns and cytomorphology typical of granulosa cell tumor. Granulosa cell tumors of adult and juvenile type may have a pseudopapillary pattern that can be confused with other ovarian tumors with a papillary architecture. Identification of areas that are more characteristic of granulosa cell tumor resolves most cases, although immunohistochemistry can be used in more problematic tumors. This phenomenon seems to be related to the cystic change that is a feature of many granulosa cell tumors.     

Morphologic spectrum of immunohistochemically characterized clear cell carcinoma of the ovary: a study of 155 cases

Establishing a diagnosis of ovarian clear cell carcinoma (O-CCC) can be subject to significant interobserver variation. Accurately diagnosing this tumor is important because of its chemoresistance and reported association with Lynch syndrome. The spectrum of the morphologic features of O-CCC has not been well described in a series composed of immunohistochemically characterized cases. A total of 155 cases diagnosed as O-CCC were retrieved from the files of 3 institutions to analyze architectural and cytologic features. The immunohistochemical features of these cases have been reported earlier. A comprehensive list of features was recorded, including, but not limited to, architectural patterns, nuclear appearance, cytoplasmic characteristics, and mitotic index. Between 1 and 13 slides were available for review for each case. The cases were divided into 2 groups based on morphologic characteristics, those with features shared by the large majority (the first group, n=138) and those that showed unusual characteristics (second group, n=17). Tumors in the first group typically showed a mixture of architectural patterns, the most frequent being papillary and tubulocystic. Papillae, usually small and round and lacking hierarchical branching and tufting or stratification of more than 3 cells, were present at least focally in almost 3 of 4 cases. The cell shape was predominantly cuboidal, not columnar. Nuclear pleomorphism and prominent nucleoli were frequently present, but never diffusely. Clear cytoplasm was found in nearly every case and hobnail cells were common. Mitoses exhibited a range from 0 to 13 with an average of 3 to 4 per 10 high power fields. The second group of tumors showed numerous unusual morphologic characteristics, despite the presence of clear cytoplasm, including those typically seen in other ovarian epithelial tumors, such as serous and endometrioid carcinoma. Eighty-nine percent of tumors from the first group showed the expected "O-CCC immunophenotype" [hepatocyte nuclear factor (HNF) positive, and estrogen receptor (ER), progesterone receptor (PR), Wilms tumor 1 (WT1) and p53 negative], whereas 4% of tumors showed HNF positivity along with focal ER or PR expression. Seven percent of tumors were not immunoreactive with these markers. Twenty-nine percent of tumors in the second group showed the O-CCC immunophenotype, whereas 24% of tumors were p53 positive, 5% of tumors were WT1 positive, and the remaining cases were negative for all markers. Ninety-seven percent (112 of 117) of HNF-positive tumors in this series were classical O-CCC. Therefore, O-CCC has characteristic morphologic features and a specific, if not unique, immunophenotype in the vast majority of the cases. Clear cell-rich tumors with features that depart from the classical morphologic appearances described herein should suggest the possibility of an alternative diagnosis.     

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.     

Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum

Reactive angioendotheliomatosis (RAE) is a rare condition characterized by cutaneous vascular proliferation that usually occurs in patients with diverse types of coexistent systemic disease. Although intravascular proliferation of endothelial cells has been considered to be the key histologic feature in RAE, other patterns of vascular proliferation have also been described. We reviewed the clinicopathologic features in 15 cases of RAE. The study group comprised eight males and seven females with an age range of 47-88 years (median 65 years). Eleven patients had coexistent systemic disease: renal disease (six patients, including three post renal transplantation); valvular cardiac disease (two patients); one patient each had alcoholic cirrhosis, glioblastoma multiforme (on chemotherapy), and rheumatoid arthritis/polymyalgia rheumatica. Six patients were iatrogenically immunosuppressed at the onset of the skin lesions. The clinical appearance included multiple erythematous macules, plaques, tumors, and ulcerated lesions, with a wide distribution but a propensity to involve limbs. Lesions had been present for 1 month to 4 years (median 4 months). Lesions resolved in four cases, improved in two cases, remained static in one case, and progressed in four cases. Two cases were recent and follow-up was not available in two other cases. Three patients died of their coexistent systemic disease with resolution, improvement, and progression of lesions, respectively. All lesions were characterized histologically by a proliferation of capillaries in the dermis, with variably diffuse (seven cases), lobular (six cases), or mixed lobular and diffuse patterns (two cases). There was marked intercase and intracase heterogeneity in histologic features. Common features included fibrin microthrombi (nine cases), reactive (fasciitis-like) dermal alterations (seven cases), and foci of epithelioid endothelium (four cases). Four of 10 cases tested showed positive immunohistochemical staining for HHV-8 latent nuclear antigen in lesional endothelial cell nuclei. This study suggests that RAE has a broader clinicopathologic spectrum than previously described. The pathogenesis of this rare disorder is unknown, but it is likely that immunologic factors play a role.     

Cribriform carcinoma of the gallbladder: a clinicopathologic study of 7 cases

Carcinomas of the gallbladder are morphologically heterogeneous. Some are similar or mimic carcinomas that commonly arise in other organs and therefore can be confused with metastatic lesions. We report here the clinicopathologic features of 7 cribriform carcinomas of the gallbladder that resemble cribriform carcinomas of the breast. Five patients were women and 2 men whose ages ranged from 31 to 72 years (average age 57 y). These 7 patients were younger than those with conventional adenocarcinomas of the gallbladder (average age for males 71 y and average age for females 72 y). Five patients had cholelithiasis. The youngest patient, a 31-year-old woman, had no gallstones. Instead, she had an osteosarcoma removed from her distal femur, 4 years before. Although the osteosarcoma in this patient may be coincidental, a true association could not be entirely excluded. None of the 4 cribriform carcinomas of the gallbladder tested showed immunoreactivity for estrogen and progesterone receptors. Three patients with high nuclear grade cribriform carcinomas died as a result of the tumor which infiltrated the liver by direct extension; 3 patients with low nuclear grade cribriform carcinomas confined to the gallbladder wall survived 4 to 7 years after cholecystectomy and 1 patient was lost to follow-up. In conclusion, this study provides support to previous observations that a small proportion of gallbladder carcinomas display an unusual but predominant cribriform pattern similar to that of some invasive breast carcinomas. In contrast to mammary cribriform carcinomas, those arising in the gallbladder occur in individuals usually with gallstones, may coexist with skeletal osteosarcoma, lack estrogen and progesterone receptors, and behave aggressively like conventional adenocarcinomas of the gallbladder.     

Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases

Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of spindle cells. Only a few cases arising in the penis have been reported. The aim of this study is to better define the clinicopathologic features of this neoplasm. A total of 400 cases of squamous cell carcinoma of the penis were reviewed from which 15 sarcomatoid carcinomas (4%) were identified. Clinical and pathologic features were evaluated in all cases. Immunohistochemical studies for expression of AE1/AE3, Cam 5.2, 34betaE12, EMA, vimentin, muscle specific actin, smooth muscle actin, desmin, S-100, p63, and p53 and in situ hybridization studies for HPV were performed in 5 cases. Information about lymph node status was available in 9 cases, and follow-up in 5 cases. The mean age was 59 years, and mean tumor size was 5 cm. Grossly, most tumors were large, polypoid, and ulcerated masses frequently affecting the glans (93%) and deeply invading corpora cavernosa (80%) and skin. Microscopically, the lesions were predominantly composed of atypical spindle cells disposed in interlacing fascicles, resembling fibrosarcoma or leiomyosarcoma, sometimes admixed with pleomorphic giant cells mimicking malignant fibrous histiocytoma. One case was predominantly composed of myxoid areas. Less frequent and focal patterns were pseudoangiomatous and epithelioid. Mitotic figures were numerous, and necrosis was prominent. Foci of heterologous differentiation toward bone (osteosarcomatous component) were present in 1 case. Four cases showed a minor mixed component of usual, papillary, verrucous, and basaloid carcinoma. Intrapenile metastasis ("satellitosis") was present in 4 tumors. One of the cases was multicentric with a separate independent focus of well-differentiated carcinoma with pseudohyperplastic features. Associated low- and high-grade squamous intraepithelial lesions were noted in 73% of the cases. Immunohistochemical studies and HPV in situ hybridization were done in 5 cases. The spindle cells were diffusely positive for vimentin and p53 and showed at least intermediate expression of 34betaE12 and p63 in all cases. EMA and AE1/AE3 were focally positive in 60% of the cases, and Cam 5.2 was focally positive in 1 case. Tumor cells failed to express muscle specific actin, smooth muscle actin, desmin, and S-100. HPV in situ hybridization was negative in all cases. Inguinal metastases were present in 89% of the cases. Two of five patients with adequate follow-up died of disease within 8 months of the diagnoses. In conclusion, penile sarcomatoid carcinomas are unusual, large, and aggressive tumors usually associated with lymph node metastasis and poor outcome. Differential diagnoses include sarcoma and melanoma. Cytokeratin 34betaE12 and p63 appear to be the more specific and sensitive markers to categorize these tumors as epithelial. Diffuse immunoreactivity for p53, compared with a more basal and focal reactivity in differentiated squamous cell carcinoma, may be indicative of a late mutation in the natural progression of the disease.     

乳腺小管癌的临床病理分析

目的 探讨乳腺小管癌的临床病理特征、诊断与鉴别诊断要点。方法 通过光镜和免疫组化方法对4例乳腺小管癌进行临床病理分析,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果 4例乳腺小管癌仅3例有可触及的肿物,另1例仅在B超下发现两个低回声肿块。镜下4例均由高分化的小管结构组成,存在开放的管腔,被覆单层上皮细胞,腺管形状不规则成角状,内含嗜碱性分泌物,可见顶浆分泌的小突起,未见肌上皮细胞及完整的基底膜成分,SMA（-）。间质增生并富于细胞。3例伴有导管内癌,其中1例伴有平坦上皮不典型增生。结论 小管癌的正确诊断需组织形态和免疫组化相结合,并与硬化性腺病、微小腺体腺病、复杂硬化性腺病/放射状瘢痕、以腺管结构为主的乳腺浸润性导管癌等病变相鉴别。     

Sinonasal acinic cell carcinoma: a clinicopathologic study of four cases

BACKGROUND: Acinic cell carcinoma is a low-grade malignant epithelial salivary gland neoplasm with a predilection for the parotid gland. To date, only 11 cases of sinonasal acinic cell carcinomas have been reported in the English-language literature. We present the clinicopathologic features of four sinonasal acinic cell carcinomas. METHODS: The demographic data and pathologic material of four patients with sinonasal acinic cell carcinoma identified from the files of the Department of Pathology at The University of Texas M. D. Anderson Cancer Center between 1984 and 2002 were reviewed. RESULTS: The four patients were two men and two women, with an age range of 42 to 65 years (mean, 54 years). The patients were initially seen with unilateral nasal obstruction. Histologically, all tumors were composed of round to ovoid cells with clear and/or basophilic granular cytoplasm and round, hyperchromatic, small, eccentrically located nuclei. The growth pattern was lobular, solid, and follicular. Histochemically, periodic acid-Schiff diastase-resistant granules were demonstrated in all cases. All patients were treated surgically. In addition, one patient received postoperative radiation. All patients are alive and well, with follow-up from 4 to 17 years. CONCLUSIONS: Sinonasal acinic cell carcinoma is a distinct low-grade carcinoma that can be distinguished from other neoplasms by light microscopy and histochemical staining methods. Pathologists and surgeons should be aware of the occurrence of this type of salivary gland neoplasm in the sinonasal tract.     

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.     

Leiomyosarcoma of the penis: a clinicopathologic study of 14 cases with review of the literature and discussion of the differential diagnosis

Primary leiomyosarcomas of the penis are very rare. To date, less than 30 have been documented in the English language literature. In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 14 cases retrieved from our files. The patients ranged in age from 43 to 62 years (mean age, 51 years) at the time of initial surgical resection. The tumors involved the prepuce (n = 1), prepuce and distal shaft (n = 1), circumcision scar line (n = 2), circumcision scar line and distal shaft (n = 1), shaft (n = 5), base of the penis (n = 3), and penis, not otherwise specified (n = 1). The lesions ranged in size from 0.5 to 6.0 cm (median size, 1.5 cm) in greatest dimension. Nine tumors were superficially located, two were of indeterminate depth, and three were deep-seated. The superficial tumors were relatively asymptomatic, and seven were reportedly present for 1 year to more than 20 years (median duration, 5 years) before medical attention was sought. In contrast, one deep-seated lesion caused dysuria and difficulty voiding, prompting the patient to seek a clinical opinion within only a few months of the apparent onset. Histologically, all tumors contained smooth muscle cells with both cytologic atypia and mitotic activity. Immunohistochemical studies were available for nine tumors, and immunoreactivity for desmin was present in all instances. All patients were initially treated with a local procedure. Follow-up information is available for 9 of the 14 patients (64%), with a median follow-up interval of 12 years 11 months. Three patients had multiple (two to four) local recurrences. Two of these patients were ultimately treated with a wide local excision or partial penectomy, and both were alive and well at last follow-up. In contrast, one patient, who had four local recurrences and refused a penectomy, developed a distant metastasis 10 months after the fourth recurrence. The best predictors of outcome are tumor depth and tumor size. Superficial leiomyosarcomas of the penis are optimally managed by wide local excision whenever this is technically feasible. Tumors with a deep-seated component may require more aggressive intervention to ensure complete removal.     

Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast

We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.