Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases

No comprehensive series has evaluated the histologic features of pheochromocytoma to separate benign from malignant pheochromocytoma by histomorphologic parameters only. Fifty histologically malignant and 50 histologically benign pheochromocytomas of the adrenal gland were retrieved from the files of the Armed Forces Institute of Pathology. The patients included 43 females and 57 males, with an age range of 3-81 years (mean 46.7 years). Patients usually experienced hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222 g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland more frequently demonstrated invasion (vascular [score = 1], capsular [score = 1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2), tumor cell spindling (score = 2), cellular monotony (score = 2), increased mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score (PASS) weighted for these specific histologic features can be used to separate tumors with a potential for a biologically aggressive behavior (PASS > or =4) from tumors that behave in a benign fashion (PASS <4). The pathologic features that are incorporated into the PASS correctly identified tumors with a more aggressive biologic behavior. Application of these criteria to a large cohort of cases will help to elucidate the accuracy of this grading system in clinical practice.     

Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases

We reviewed 223 localized fibrous tumors of the pleura and divided them histologically into 141 benign and 82 malignant neoplasms. The criteria used for a judgement of malignancy were high cellularity and mitotic activity (more than four mitotic figures per 10 high-power fields), pleomorphism, hemorrhage, and necrosis. The tumors occurred equally in both sexes, most commonly in the sixth to seventh decades of life. Presenting symptoms included chest pain, dyspnea, and cough; they were observed in three-fourths of patients with a malignant tumor. One in every four of these patients had hypoglycemia, clubbed digits, or pleural effusion. Two-thirds of the tumors were attached to visceral pleura, often by a pedicle. The rest arose from the parietal pleura of the chest wall, diaphragm, or mediastinum. Neoplasms in these atypical sites, together with fissural lesions and tumors "inverted" into peripheral lung, were more often malignant. Most neoplasms measured 5-10 cm and weighed 100-400 g. Microscopically, the "patternless pattern," or hemangiopericytic type, was seen in the majority of cases, and mixed patterns were seen in nearly 40% of tumors. Of the 169 tumors where follow-up was available, all of the benign and 45% of the malignant tumors were cured by simple excision. Patients surgically cured of a malignant neoplasm had pedunculated or well-circumscribed lesions. However, 55% of patients with malignant tumors succumbed to their disease secondary to invasion, recurrence, or metastasis. Resectability is the single most important indicator of clinical outcome. No tumor expressed epithelial differentiation, either immunohistochemically or ultrastructurally; therefore, we favor the term "localized fibrous tumor" of pleura instead of "localized mesothelioma."     

Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors

Occasional glomus tumors display unusual features, such as large size, deep location, infiltrative growth, mitotic activity, nuclear pleomorphism, and necrosis. Although a small number of purportedly malignant glomus tumors have been described, histologic criteria for malignancy in glomus tumors have never been elaborated. The authors studied 52 unusual glomus tumors (retrieved from their consultation files) previously diagnosed as "atypical" or "malignant" by virtue of nuclear atypia, infiltrative growth, or mitotic activity. They evaluated size, depth, growth pattern, cellularity, nuclear grade, number of mitotic figures per 50 high-power fields (HPF), atypical mitotic figures, vascular space involvement, and necrosis to define criteria for malignancy in glomus tumors. Estimated relative risk was calculated and the Fisher exact test was used for statistical analysis. The 27 female patients and the 25 male patients ranged in age from 8 to 83 years (median age, 43 years). The tumors measured from 0.2 to 12 cm (median size, 2 cm) and occurred predominantly in the extremities, in both the superficial (n = 35) and deep (n = 17) soft tissues. Atypical features were usually observed centrally with a rim of benign-appearing glomus tumor. Follow-up information (n = 35; range, 5 months-23 years; mean 5.5 years) showed seven recurrences, eight metastases, and seven deaths from disease. Five-year cumulative metastatic risk increased significantly for tumors with a deep location (p = 0.005), with a size of more than 2 cm (p = 0.004), and with atypical mitotic figures (p = 0.004). Mitotic activity of more than 5 mitoses/50 HPF, high cellularity, the presence of necrosis, and moderate to high nuclear grade approached but did not reach significance. High nuclear grade alone, infiltrative growth, and vascular space involvement were not associated with metastasis. The authors propose the following classification scheme and criteria. Malignant glomus tumor: Tumors with a deep location and a size of more than 2 cm, or atypical mitotic figures, or moderate to high nuclear grade and > or =5 mitotic figures/50 HPF. Symplastic glomus tumor: Tumors with high nuclear grade in the absence of any other malignant feature. Glomus tumor of uncertain malignant potential: Tumors that lack criteria for malignant glomus tumor or symplastic glomus tumor but have high mitotic activity and superficial location only, or large size only, or deep location only. Glomangiomatosis: Tumors with histologic features of diffuse angiomatosis and excess glomus cells. Using this classification scheme, metastasis was observed in 38% of tumors fulfilling the criteria for malignancy. In contrast, metastatic disease was not seen in any specimen classified as symplastic glomus tumor, glomus tumor of uncertain malignant potential, or glomangiomatosis.     

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.     

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.     

Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors

A series of 43 adrenocortical tumors was analyzed using nine histologic features. Mitotic activity, especially with atypical forms, and venous invasion correlated best with metastasizing or recurring tumors; however, no single criterion was useful alone. The combination of the following nine criteria was most useful in distinguishing malignant from benign tumors: nuclear grade III or IV; mitotic rate greater than 5/50 high-power fields; atypical mitoses; clear cells comprising 25% or less of the tumor; a diffuse architecture; microscopic necrosis; and invasion of venous, sinusoidal, and capsular structures. None of the 24 tumors with two or less of these criteria metastasized or recurred, while all but one of the 19 tumors with four or more of these criteria either recurred or metastasized.     

Deep "benign" fibrous histiocytoma: clinicopathologic analysis of 69 cases of a rare tumor indicating occasional metastatic potential

Benign fibrous histiocytoma (FH) is one of the most common mesenchymal neoplasms of the skin. Several histologic variants of cutaneous FH have been described, some of which also have distinct clinical features including a propensity for local recurrence. Deep benign FH is an uncommon and poorly recognized clinical subtype that arises in subcutaneous or deep soft tissue. Only a single small series of these neoplasms has been published, and their clinical behavior is not well characterized. In this study, we report the clinicopathologic features of 69 deep FH retrieved from our consultation files. The patients included 41 males and 28 females, ranging in age from 6 to 84 years (median, 37 y). The most common anatomic location was the extremities (58%); the remainder arose on the head and neck (22%), trunk (11%), and in the deep soft tissue of the retroperitoneum, mediastinum, or pelvis (9%). All lesions arising in nonvisceral soft tissue were subcutaneous. The tumors ranged from 0.5 to 25 cm in size (median, 3.0 cm) and were well circumscribed grossly and microscopically. All tumors were composed of bland ovoid to spindle cells arranged in a storiform pattern with admixed lymphocytes. Multinucleate giant cells, osteoclastic giant cells, and/or foam cells were present in 59% of cases, whereas the other 41% were cytologically monomorphic, often resembling cellular FH. Other common findings included a hemangiopericytomalike vascular pattern (42%) and stromal hyalinization (39%). Four cases were classified as atypical deep FH due to the presence of scattered markedly pleomorphic spindle cells within an otherwise histologically typical lesion. The median mitotic rate was 3/10 HPF; 10 cases (14%) had >10 mitoses/10 HPF. Necrosis (2 cases) and lymphovascular invasion (1 case) were rare. Immunohistochemistry revealed expression of CD34 in 20/50 cases (40%), smooth muscle actin in 15/40 (38%), and focal desmin in 1/12 (8%). Of the 37 patients for whom clinical follow-up was available (median, 40 mo), 8 (22%) had a local recurrence; in all 8 cases, the tumor had been marginally or incompletely excised. Metastases occurred in 2 patients (5%), both of whom ultimately died of disease; however, this number is likely exaggerated due to consultation bias. The metastasizing tumors were large (6 and 9 cm) and 1 had tumor necrosis but they were otherwise histologically identical to the nonmetastasizing lesions. In summary, deep FH has many histologic features in common with cutaneous cellular FH; however, it usually has a more diffusely storiform pattern than the latter, is well circumscribed, and may have striking hemangiopericytomalike vessels. Similar to the cellular, aneurysmal, and atypical variants of FH, deep FH recurs in approximately 20% of cases and may rarely metastasize.     

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.     

Stromal testis tumors in children: a report from the prepubertal testis tumor registry.

PURPOSE: Stromal testis tumors are rare and generally exhibit a benign behavior in prepubertal patients. We reviewed the Prepubertal Testis Tumor Registry to elucidate further the behavior of these tumors. MATERIALS AND METHODS: Epidemiological and clinical information on stromal testis tumors was compiled and reviewed from the Prepubertal Testis Tumor Registry. In addition, original pathology reports were requested for all patients registered as having undifferentiated stromal tumors. RESULTS: There were 43 patients registered with stromal tumors. Of the 21 patients with unspecified stromal tumors pathology reports were obtained on 11. Eight patients had truly mixed or undifferentiated stromal tumors. Mean patient age at presentation was 38 months (Leydig cell 70, Sertoli cell 52.5, juvenile granulosa cell 1.5 and mixed/undifferentiated 41.2). No patient with a Leydig cell, Sertoli cell or juvenile granulosa cell tumor had metastases at presentation or metastatic disease during an average 24.6 months of followup. One undifferentiated tumor demonstrated malignant behavior by presenting with metastatic disease. Pathological examination revealed a poorly differentiated tumor with extension into the adjacent tunica and frequent mitotic figures. While other stromal tumors displayed mitotic figures, none showed local invasion. CONCLUSIONS: Stromal testis tumors are rare. Data from the Prepubertal Testis Tumor Registry confirms the benign behavior of most of these tumors. However, undifferentiated stromal tumors may exhibit metastatic behavior. A high index of suspicion is appropriate when there are a large number of mitotic figures, the tumor is poorly differentiated or when local invasion is present in the primary tumor. Metastatic evaluation and close followup are warranted for this select group of patients.     

Pathologic features of prognostic significance in adrenocortical carcinoma

There are currently no well-established pathologic prognostic factors helpful in distinguishing low versus high grade adrenocortical carcinomas. The effect of 11 pathologic parameters on survival was investigated in 42 cases of adrenocortical carcinoma. Only one variable, mitotic rate, had a strong statistical association with patient outcome. The 21 patients with carcinomas with greater than 20 mitoses per 50 high power fields (hpf) had a median survival of 14 months, whereas the 21 patients with carcinomas with less than or equal to 20 mitoses had a median survival of 58 months (p less than 0.02). The presence of atypical mitoses, capsular invasion, tumor weight greater than 250 g, and size greater than 10 cm each showed a marginal statistical association with poor survival (p less than 0.06), whereas other features assessed, such as nuclear grade, presence of necrosis or of venous or sinusoidal invasion, character of the tumor cell cytoplasm, or architectural pattern, showed no statistical significance in predicting survival. It is proposed that adrenal cortical carcinomas with greater than 20 mitoses be designated high grade, whereas tumors with less than or equal to 20 mitoses be designated low grade.     

Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. A clinicopathologic study of ten cases

We evaluated the clinicopathologic features of 22 smooth-muscle tumors of the uterine corpus that had at least five mitoses per 10 high-power fields (HPF) in the most active areas. Ten women were alive and well without tumor recurrence 15 months to 11 years after diagnosis (median, 6 years); these patients were referred to as the "clinically benign" group. The other 12 women had "clinically malignant" disease: 9 died of recurrent or metastatic tumor 3 months to 4.5 years after diagnosis (median, 16 months), and 3 are alive with disease 4-12 months after diagnosis. Significant clinical and pathologic differences were observed between patients in the "benign" and "malignant" groups. We found that mitotic activity in the range of 5 to 15 mitoses per 10 HPF was not a reliable predictor of aggressive behavior in tumors that lacked marked cytologic atypia and that by all other clinical and pathologic criteria were leiomyomas. An unfavorable prognosis among the mitotically active neoplasms could be predicted by a constellation of clinicopathologic features, including postmenopausal status, a clinical or intraoperative impression of cancer by the surgeon, extension of tumor beyond the uterine corpus, size greater than 10 cm, marked cytologic atypia, invasive borders, necrosis, and mitotic counts exceeding 20 per 10 HPF.     

Angiosarcomas arising in the viscera and soft tissue of children and young adults: a clinicopathologic study of 15 cases

Angiosarcomas are rare tumors that predominantly affect adult and elderly patients and pursue an aggressive clinical course with high mortality. Although angiosarcomas are well described in a variety of clinical settings, they have been incompletely characterized. We identified 15 high-grade angiosarcomas arising from the viscera and soft tissue of patients 21 years old and younger from institutional and consultation files. Both clinical (patient age, tumor site, tumor size, tumor focality) and histologic features including growth pattern (vasoformative vs. solid), nuclear grade (high vs. low), mitotic rate (mitotic figures/10 high-power fields), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid) were assessed. Tumors arose in both sexes (8 males; 7 females); age at diagnosis ranged from 3 months to 19 years (mean, 10 y, 5 mo; median, 11 y). Tumors were located in the mediastinum (7), visceral organs (2 in liver, 1 in spleen), breast (2), mesentery (1), pelvis (1), and deep soft tissue of upper extremity (1). Tumor size was documented for 8 patients (range 3.5 to 13 cm; mean 8.1 cm). Eight cases showed epithelioid morphology and 7 cases were primarily spindled. Of 8 cases assessed for podoplanin expression by immunohistochemistry, 7 were negative and 1 was positive. Clinical follow-up was obtained for all patients: 10 (67%) died of disease (range, 27 mo to 11 y; mean, 6 y 8 mo) and 4 patients were alive without disease (range, 27 to 132 mo; mean, 79 mo). Although extremely rare, angiosarcomas do affect children and young adults and this diagnosis should be considered in atypical vascular tumors occurring in the mediastinum and those with brisk mitotic activity and/or necrosis.     

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.     

Gastric stromal tumors: a clinicopathologic study of 77 cases with correlation of features with nonaggressive and aggressive clinical behaviors

Gastrointestinal stromal tumors are a heterogeneous group of neoplasms that have clinical and histologic features that vary depending on their location within the gastrointestinal tract. Prediction of clinical behavior in this group of tumors is notoriously difficult, and the same criteria for malignancy do not necessarily apply to stromal tumors from different sites within the gastrointestinal tract. Using known clinical behavior with long-term follow-up, we attempted to determine which features, if any, are associated with clinical behavior in stromal tumors arising in the stomach, the most common site for such tumors. Seventy-seven gastric stromal tumors were studied and classified as "adverse outcome (AO) tumors" (malignant) or "nonadverse outcome tumors" (benign) based on their known clinical outcome. AO was defined as metastasis and/or death due to tumor. Patients with a non-AO had at least 5 years of tumor/metastasis-free follow-up. Thirty-seven patients had an AO (follow-up [metastasis at presentation] 0-73 months; median 6 months), and 40 patients had a non-AO (follow-up 60-264 months; median 84 months). All cases were reviewed by two authors (J.R.G., H.D.A.), who were blinded to clinical outcome and gross features, and classified as histologically benign or not benign using preset, defined histologic criteria based upon the authors' prior experience with a large number of these tumors. If the tumor did not fit with either the characteristic cellular spindle cell or benign epithelioid cell patterns, the tumor was classified as not benign. Clinical outcome was then correlated with the histologic designation to determine if these preset criteria were valid. The authors were able to accurately classify the tumors as benign or not benign with a sensitivity of 100% and a specificity of 92%. In addition, for all cases individual morphologic and clinical features were examined. Features associated with an AO included tumor size >/=7 cm, high cellularity, mucosal invasion, high nuclear grade, mitotic counts >/=5/50 high power fields, mixed cell type, and the presence of a myxoid background and/or absence of stromal hyalinization. By recognizing several well-defined patterns of benign gastric stromal tumors and the myriad of individual features shown to correlate with an AO, one can better predict the clinical behavior of gastric stromal tumors.     

Ovarian steroid cell tumors (not otherwise specified). A clinicopathological analysis of 63 cases

The clinical and pathological features of 63 steroid cell tumors, not otherwise specified, were reviewed. The patients ranged in age from 2 1/2 to 80 years. The most common initial manifestation was virilization (41%); four patients had estrogenic manifestations, and four had hypercortisolemia with Cushing's syndrome. The tumors, 6% of which were bilateral, ranged from 1.2 to 45 cm in greatest dimension. Microscopic examination revealed two types of cells, which had overlapping features: those with abundant eosinophilic cytoplasm and those with vacuolated cytoplasm. Fat stains were positive in 75% of the 16 cases in which they were performed. Follow-up data ranging from 1 to 19 years (average 5.2 years) in duration were available for 50 patients. In 24 cases, the tumor was designated probably benign (no evidence of spread beyond the ovary within 3 or more years postoperatively). In 18 patients, the tumor was clinically malignant. The best pathological correlates of malignant behavior were: the presence of two or more mitotic figures per 10 high power fields (92% malignant); necrosis (86% malignant); a diameter of 7 cm or greater (78% malignant); hemorrhage (77% malignant); and grade 2 or 3 nuclear atypia (64% malignant).     

Myoepithelial Tumors of Salivary Gland: A Clinicopathologic and Immunohistochemical Study of 15 Patients with MIB-1 Correlation

Myoepithelial neoplasms are rare tumors of the salivary glands with predominant myoepithelial differentiation and a broad histologic spectrum. Their histological features, immunohistochemical profile and biological behavior are not well characterized and pose a diagnostic challenge. A total of 15 myoepithelial tumors, diagnosed during 2012 and 2019 were subcategorized and correlated with MIB-1 labeling index (LI) and various histological parameters. Immunohistochemical stains for MIB-1 and other antibodies were performed. Statistical analysis was done by chi-square test, Fisher’s exact test and Kaplan Meier curve. Nine patients were male and six were female with the median age of 44 years (range 21–83 years). Of the 15 patients, 6 cases were classified as myoepithelioma (ME) and 9 cases as myoepithelial carcinoma (MECA). Parotid gland was the most common site (46.7%) followed by the palate. MEs showed well circumscribed tumor borders whereas MECAs exhibited focal capsular to extensive invasion into adjacent tissues. Epithelioid cell morphology was most common followed by mixed cell morphology. MIB-1 LI was significantly associated with invasive tumor borders, necrosis and high mitosis. Increased frequency of recurrence was noted with high MIB-1 LI, though it was not statistically significant. MIB-1 LI was high in nearly all MECAs with focal capsular to extensive invasion while low in MEs. Myoepithelial tumor with multinodular growth pattern and focal capsular invasion may have an indolent behavior if mitotic activity and MIB-1 LI is low. Early diagnosis and treatment of MECAs significantly improves the patient''s survival and prognosis.     

Atypical intradermal smooth muscle neoplasms: clinicopathologic analysis of 84 cases and a reappraisal of cutaneous "leiomyosarcoma"

Atypical or mitotically active dermal smooth muscle neoplasms are uncommon lesions, which are most often termed "cutaneous leiomyosarcoma," although preexisting-mostly small-series suggest a low risk of aggressive behavior. To further investigate these tumors, 84 cases from consultation and institutional files were analyzed for pathologic and clinical characteristics. There was a striking male-to-female preponderance (4.3:1), with a mean age of 56 years (range, 6 to 82y). Nine patients had a history of malignancies (6 of the skin). Tumors measured 1.3 cm on average and were predominantly located on the trunk (32) and lower extremities (30). Histologically, all tumors were confined to the dermis or showed only very superficial, focal subcutaneous extension. The majority showed an infiltrative growth pattern with fascicles of atypical eosinophilic spindle cells ramifying between dermal collagen fibers. Primary tumors showed a mean mitotic rate of 4.7/10 high-power fields. By the Fédération Nationale des Centres de Lutte Contre le Cancer grading system, 97% of primary tumors were grade I lesions, with only 3% showing necrosis. All tumors were immunopositive for smooth muscle actin; 98% expressed desmin, 90% caldesmon, and 45% pankeratin (usually focal). Follow-up in 52 cases (mean, 51 mo) showed no metastases or tumor-related deaths. Eighteen tumors showed local recurrence at a mean interval of 43 months; 12 of the recurrent lesions showed positive margins in the primary excision and 1 showed margins <0.2 cm. Margin status was not available for the other 5 cases, which recurred locally. Recurrent tumors showed, on average, 13.7 mitoses/10 high-power fields. Of recurrences, 47% were grade I lesions, 35% were grade II, and 18% were grade III, and 28% showed necrosis. The primary excision of tumors, which later recurred, showed no difference in grade, presence of necrosis, or mitotic rate, compared with those that did not recur; there were no discernible clinical differences either. In summary, these tumors, when confined to the dermis or showing only minimal subcutaneous involvement, seem to carry no evident risk of metastasis; hence, the designation "sarcoma" is inappropriate. Margin status is the most important predictor of recurrence. On excision with clear margins, the risk of local recurrence is very low. Hence, we propose the term "atypical intradermal smooth muscle neoplasm" as being more appropriate.     

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.