Marked Cytologic Atypia Research Articles

Proximal-type Epithelioid Sarcoma of the Pelvis

Epithelioid sarcoma is a rare malignant soft-tissue sarcoma with an unknown histiogenesis, typically presenting as a subcutaneous or deep dermal mass lesion in the distal portions of the extremities of young adults. Recently, a more aggressive, so-called 'proximal-type' epithelioid sarcoma has been reported. In contrast to conventional epithelioid sarcoma, the proximal type is characterized by a predominantly large cell epithelioid cytomorphology, marked cytologic atypia, and frequent occurrence of rhabdoid features in most patients. Proximal-type epithelioid sarcoma has a predilection for appearing in the genitalia, especially the vulva, penis, pelvis and buttocks. Also this lesion appears to be somewhat more aggressive or at least metastasizes earlier than the conventional epithelioid sarcoma. We report a 13-year-old girl who presented with a huge mass filling the pelvic cavity which was painful, hard and fixed on palpation, and was radiologically diagnosed as a malignant germ cell tumors on the CT scan. The mass was surgically excised and pathologically proved to be an proximal-type epithelioid sarcoma of unknown origin.

Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas.

Ovarian endocervical-type (müllerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death. The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion < or =5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases. Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease. In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma. As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type. Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.

Gynecomastia With Marked Cellular Atypia Associated With Chemotherapy A Diagnostic Pitfall in Fine-Needle Aspiration

c Gynecomastia is a common benign male breast disease, which may exhibit mild cellular atypia in cytology specimens. However, marked cytologic atypia can be seen in gynecomastia superimposed by chemotherapy. The case described in this report demonstrated severe cytologic atypia of gynecomastia mimicking carcinoma in a patient treated with chemotherapy for acute leukemia. A distinct cytologic feature helpful in avoiding the diagnostic error is described, namely, atypical cells admixed with bland ductal cells and appearing at a different plane. The importance of applying strict diagnostic criteria in breast cytology and clinical correlation is also emphasized. (Arch Pathol Lab Med. 2002;126:613‐614)

Villous adenoma of the common hepatic duct

A 78-year-old woman presented with painless jaundice 8 months after laparoscopic cholecystectomy for acute calculous cholecystitis. An intraoperative cholangiogram did not visualize the proximal extrahepatic bile duct. ERCP showed a 2-cm lobulated fixed filling defect within the common hepatic duct distal to the hepatic bifurcation (A). The papilla was in a large peripapillary diverticulum and attempts to obtain a tissue diagnosis were unsuccessful. A cytologic specimen, obtained with a brush by means of a percutaneous approach, was interpreted as containing atypical glandular cells. Biopsy specimens obtained at subsequent percutaneous cholangioscopy showed mucinous debris, degenerative cells, and acute inflammatory fibrous tissue. At exploratory laparotomy, a frozen section biopsy specimen was interpreted as consistent with villous adenoma. The bile duct was resected and a hepaticojejunostomy performed. Histopathologic evaluation of the resection specimen (B) showed a villous adenoma with marked cytologic atypia and rare foci of superficially invasive adenocarcinoma. Five lymph nodes were negative for metastasis. The patient recovered from the surgery and is doing well.

Benign Atypical Junctional Melanocytic Hyperplasia Associated with Intradermal Nevi: A Common Finding That May Be Confused with Melanoma In Situ

Over the past few years, consultation cases thought to represent melanoma in situ have been received that consisted of otherwise normal intradermal nevi with an abnormal but benign junctional proliferation of melanocytes that we have termed benign atypical junctional melanocytic hyperplasia. In order to evaluate the incidence of this feature, 400 cases of intradermal nevi were reviewed. Of these, 25 (6.2%) qualified for inclusion, making this a rather common phenomenon. Clinically, patient ages ranged from 18 to 64 years (mean, 35 years), with a male to female ratio of 1:1. Face (40%) and back (32%) were the most common locations. Histologically, the lesions were predominantly dome-shaped with an intradermal component consisting of conventional nevus cells. Most importantly, each lesion exhibited prominent individual nevomelanocytic cells dispersed at uneven intervals along the dermoepidermal junction in insufficient numbers to be considered compound nevi. The cells exhibited abundant pale to clear cytoplasm, an increased nuclear:cytoplasmic ratio, and often exhibited prominent nucleoli. However, these lesions could be distinguished from melanoma in situ by the lack of several features including lateral spread, upward epidermal migration, marked cytologic atypia, finely granular “smoky” melanin pigment, mitotic figures, and a subjacent host inflammatory response. All cases behaved in a benign fashion. Although benign atypical junctional melanocytic hyperplasia is a relatively common histological curiosity, it is a potential pitfall in the diagnosis of pigmented lesions.

A diagnostic approach to smooth muscle tumours of the uterus

Most uterine smooth muscle neoplasms are easy to diagnose as benign or malignant. The constituent cells of these neoplasms phenotypically resemble the smooth muscle cells of the normal myometrium (‘standard’ smooth muscle differentiation). The vast majority of leiomyomas feature a low mitotic index, cytologically bland, uniform cells and no necrosis. In contrast, the majority of the much less common leiomyosarcomas feature a high mitotic index, cytologically bizarre cells and necrosis. A minority of smooth muscle proliferations of the uterus pose problems. Those with standard smooth muscle differentiation may feature the puzzling combinations of mitotic index, marked cytological atypia and necrosis. In addition, non-standard smooth muscle differentiation may be encountered. The authors set out guidelines for predicting the clinical behaviour of these problematic neoplasms using a multivariate classification rule employing mitotic index, cytological atypia and the presence or absence of necrosis having a certain pattern.

Cytology of thymomas

Aspirates of thymomas are distinguishable from other lesions and fine-needle aspiration (FNA) is a proven method for investigating mediastinal masses. Thirty-four cytology specimens of thymomas from 31 patients were examined. Corresponding surgical materials were available in 32 cases. Ten cases were benign and 22 were malignant. Cytologic features of these thymomas were correlated with various histologic classification systems and with biologic behavior. Dual epithelial and lymphoid populations and irregular cohesive tissue fragments of varying proportions of lymphoid and epithelial cells were characteristic of all aspirates. Using the Lattes-Bernatz classification, 10 cases predominately were lymphocytic, 3 cases predominately were epithelial, 3 cases predominately were spindle, 15 cases predominately were mixed, and 1 case was a thymic carcinoma. In the Muller-Hermelink classification, 3 cases were medullary, 12 were mixed, 8 predominately were cortical, 2 were cortical, 6 were well differentiated thymic carcinoma, and 1 was a poorly differentiated thymic carcinoma. In the majority of the cases the epithelial cells were round to oval. Spindle cells and a mixture of round to oval and spindle cells also were observed. No cytologic feature was found to correlate significantly with any classification scheme. Necrosis was present in 5 of the 32 aspirates, most frequently in malignant tumors. Thymomas showing predominately spindle cells frequently were encapsulated. Tumors with predominantly round to oval cells or a mixed population behaved more aggressively than those with spindle cells. Tumors that were well encapsulated and benign clinically tended to possess benign-appearing nuclei. Among the 22 invasive or malignant lesions, 8 exhibited moderate to marked cytologic atypia and 14 showed little or no atypia. No atypia was observed in benign tumors. The presence of cytologic atypia of epithelial cells may be helpful in predicting aggressiveness. However, the absence of atypia and necrosis may not imply a benign course. Correlation with clinical and radiographic findings should be sought.

子宮内膜擦過細胞診にて腫よう細胞を認めた子宮平滑筋肉腫の１例

We describe a case of uterine leiomyosarcoma associated with acute infection. A 56-year-old woman presented with atypical genital bleeding. Endometrial cytology revealed isolated bizarre spindle-shaped or fibrous cells. The cytological diagnosis was malignant mesenchymal tumor (probably uterine leiomyosarcoma). She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Macroscopically, the intramural tumor showed massive hemorrhagic areas and necrosis. Histologically, the tumor showed smooth muscle differentiation with marked cytologic atypia and increase in mitotic figures, and the diagnosis was leiomyosarcoma.

Fine-needle aspiration cytology of spindle cell lesions of the breast.

Fine-needle aspiration biopsy (FNA) has been successful in diagnosing epithelial lesions of the breast. Its role in the evaluation of spindle cell and mesenchymal lesions of the breast, which include a variety of benign and malignant conditions, is less clear. This article discusses the cytologic features and differential diagnosis of these lesions, as well as the potential diagnostic pitfalls associated with them. FNAs of the breast, in which a spindle cell or mesenchymal component was a key or dominant feature, were retrieved. Fibroadenomas without cellular stroma and typical lipomas were excluded. Forty-six aspirates (0.87%) in a series of 5306 breast FNAs contained a significant spindle cell or mesenchymal component. The aspirates were classified into 4 categories: 1) reactive conditions, including 2 diabetic mastopathies, 3 granulation tissue specimens, and 7 granulomatous lesions; 2) benign neoplastic conditions, including 1 mammary hamartoma, 1 dermatofibroma, 1 fibromatosis, 2 granular cell tumors, 2 angiolipomas, and 7 cellular fibroadenomas; 3) low grade malignant neoplastic lesions, including 10 low grade phyllodes tumors; and 4) high grade malignant neoplastic lesions, including 1 metaplastic carcinoma with chondroid stroma, 1 pleomorphic liposarcoma, 2 malignant fibrous histiocytomas, 2 osteosarcomas, and 4 metastatic melanomas. A specific diagnosis was rendered in 38 cases (82.6%). The mammary hamartoma was diagnosed as fibrocystic changes; the dermatofibroma as benign spindle cell lesion, not otherwise specified (NOS); and the primary osteosarcoma as an atypical spindle cell proliferation, NOS. The reactive ductal epithelial cells in one of the granulomatous mastitis specimens, as well as the hyperplastic ductal epithelial cells in one of the phyllodes tumors, were interpreted as atypical ductal proliferation. The marked cytologic atypia displayed by one granular cell tumor was interpreted as low grade adenocarcinoma and the primary liposarcoma as poorly differentiated carcinoma. Breast lesions with a significant spindle cell or mesenchymal component are rarely encountered in FNA and constitute a heterogeneous group that may pose a diagnostic dilemma. FNA should be the initial diagnostic procedure for investigating these lesions, as a specific diagnosis was rendered in the majority of cases. Cancer (Cancer Cytopathol)

Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors: atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas.

Histologic criteria for the distinction of ovarian mucinous borderline tumors (MBTs) from invasive mucinous carcinomas (MUCCAs) and the definitions of intraepithelial (noninvasive) carcinoma and microinvasion are controversial. Accurate assessment of the behavior of these tumors has been obscured by inclusion of cases of pseudomyxoma peritonei (PMP), an entity of extraovarian origin, and misclassification of the ovarian tumors in PMP and metastatic mucinous carcinomas (METCAs) as either advanced-stage MBTs or primary ovarian MUCCAs. One hundred thirty-six intestinal-type ovarian mucinous tumors without PMP were evaluated for the presence of stromal invasion, marked cytologic atypia, epithelial stratification of more than three cell layers, and necrosis. Criteria for the diagnosis of MBT, MBT with intraepithelial carcinoma, MBT with microinvasion (MIBT), MUCCA, and METCA were established and correlated with behavior. Twenty-three (59%) of 39 patients whose tumors had stromal invasion of more than 5 mm died of disease. Stromal invasion of more than 5 mm was the sole feature that correlated with a poor prognosis. In the absence of this feature, marked cytologic atypia, epithelial stratification of more than three layers, microinvasion (<5 mm), or necrosis did not have an adverse effect on survival. Tumors were classified as MBT (n = 65; 48%) based on absence of stromal invasion, regardless of degree of cytologic atypia or epithelial stratification; of these, 28 (43%) qualified as intraepithelial carcinoma based on epithelial stratification of more than three cell layers or marked cytologic atypia. Tumors with stromal invasion of less than 5 mm were classified as MIBT (n = 8; 6%). Tumors with stromal invasion of more than 5 mm were classified as MUCCA (n = 24; 18%). Tumors with a nodular pattern of stromal invasion, morphology inconsistent with ovarian origin, or a primary site elsewhere were classified as METCA (n = 35; 26%). Four tumors could not be definitively classified. Of the 86 cases with follow-up (median, 33 months) all MBTs (n = 44) and MIBTs (n = 6) were stage I, with 5-year survival rates of 100%. MUCCAs (n = 17) that were stage I had a 5-year survival rate of 91%; all patients with advanced-stage MUCCA died of disease. Five-year survival rate for METCAs (n = 19) was 11%. METCAs were more common than MUCCAs but can mimic MUCCAs and MBTs clinically and histologically. In the absence of a primary site elsewhere, METCA should be strongly suspected when there is bilateral surface involvement and a characteristic nodular pattern of invasion. It is important to recognize this pattern because 5-year survival rate for METCA (11%) was substantially less than that of MUCCA (all stages, 51%) and MBT (100%). Because all MBTs, regardless of degree of atypia or stratification, were stage I and benign, we prefer to designate them as atypical proliferative mucinous tumors. Marked cytologic atypia, epithelial stratification of more than three layers, and microinvasion (<5 mm) had no effect on the behavior of MBT. Noninvasive mucinous tumors with marked cytologic atypia or excessive epithelial stratification can be interpreted as atypical proliferative tumors with intraepithelial carcinoma and those with microinvasion can be designated as atypical proliferative tumors with microinvasion; these tumors appear to represent transitional stages in ovarian mucinous carcinogenesis.

Lymphoid lesions of the gastrointestinal tract: a histologic, immunophenotypic, and genotypic analysis of 49 cases.

The diagnosis of gastrointestinal (GI) lymphoid infiltrates can be challenging when based only on conventional microscopic assessment. When marked cytologic atypia is present, a diagnosis of malignant neoplasm is readily made; however, the distinction between a low-grade malignant neoplasm and a reactive process is much more difficult. If unfixed tissue is available, immunohistologic or genotypic methods that are usually aimed at defining B-lymphocytic monotypism can be applied. However, paraffin-embedded tissue has generally been deemed unsuitable for these techniques. We assessed the value of a panel of immunohistochemical stains and a seminested polymerase chain reaction (PCR) for the analysis of lymphoid infiltrates in routinely processed GI biopsy specimens from 49 archival cases, including morphologically benign, indeterminate, and overtly malignant lesions. Clinical outcome was used as the retrospective diagnostic standard; end points were death (of lymphomatous disease or otherwise) and clinical evidence of lymphoma. According to light microscopic criteria, 19 cases were classified as benign, 17 as malignant, and 13 as atypical. Immunophenotyping correctly identified 28 of 31 benign and 14 of 18 malignant lesions (7 cases had an indeterminate immunoprofile). Genotypic analysis correctly identified 12 of 18 malignant and 29 of 31 benign lesions, but spurious monoclonal bands were produced by PCR amplification of 2 of the latter 31 cases. No single technique exists for correct categorization of all paraffin-embedded specimens of GI lymphoid infiltrates. We recommend a sequential approach to the use of available diagnostic modalities.

Cytology of "significant" breast ductal proliferations.

To determine the usefulness of fine needle aspiration cytology in diagnosing breast ductal proliferations that fall short of invasive cancer (hyperplasia, atypia and in situ carcinoma). This study was a comparison of the cytomorphology and histomorphology of 30 palpable breast lesions in which an initial fine needle aspiration diagnosis of ductal hyperplasia or atypia was based on available criteria. Among six patients, a cytologic diagnosis of mild hyperplasia, based on monolayered cell sheets, was confirmed in five. Fourteen cytologic reports of moderate hyperplasia, based on three-dimensional cell clusters, cell overlap and sublumens, were confirmed in 12. A cytomorphologic diagnosis of atypical ductal hyperplasia was rejected in four of seven patients. Three cases of marked cytologic atypia were diagnosed histopathologically as ductal carcinoma in situ. In breast aspirates, three-dimensional ductal cell clusters, a swirling pattern of growth, sublumens, cell dyscohesion and conspicuous nuclear overlap indicate moderate ductal hyperplasia. Ductal atypia should be diagnosed only on such nuclear features as anisonucleosis, irregular nuclear membranes, clumped chromatin and eosinophilic macronucleoli. Cytologists should highlight those features which are important to diagnose breast proliferations as "significant" from the viewpoint of progressing to invasive cancer and not attempt too fine a classification of these lesions.

Pagetoid Spitz Nevus

A distinctive variant of melanocytic growth pattern is described, which appears to be related to Spitz nevus and is characterized by a mainly intraepidermal proliferation of large epithelioid melanocytes with a predominantly pagetoid distribution. This melanocytic lesion appears clinically as a small (< 0.4 cm) pigmented macule in young patients. Histologically, this lesion needs to be distinguished primarily from in situ or microinvasive malignant melanoma with pagetoid spread. Features favoring nevus over melanoma include small size, circumscription, symmetry, even distribution of cells, and lack of marked cytologic atypia.

Carotid body tumor mimicking adenocarcinoma on fine-needle aspiration.

We report an 86-year-old woman who presented with a 6-month history of a mass in the left side of her neck. MRI and MRI angiography favored a diagnosis of a neural tumor. FNAB showed a large cluster of cohesive, pleomorphic cells with intranuclear inclusion bodies; a diagnosis of adenocarcinoma was favored. At surgery, a 7 x 5 x 2.5 cm, firm, encapsulated mass was excised. Microscopically, the richly vascularized tumor had characteristics of a CBT, with large pleomorphic chief cells and spindle-shaped sustentacular cells in small, poorly formed nests. The chief cells were strongly immunoreactive for neuron-specific enolase and chromogranin, and focally positive for neurofilament, enkephalin, somatostatin, and beta-endorphin. The sustentacular cells were strongly immunoreactive for S-100 protein and glial fibrillary acidic protein and focally positive for vimentin. Ultrastructurally, the chief cells contained abundant neurosecretory granules. We emphasize that CBT must be included in the differential diagnosis of lateral neck masses. The distinction from adenocarcinoma is difficult on FNAB. The marked cytological atypia in an aspirate of a CBT does not indicate malignancy and may lead to an erroneous diagnosis.

Renal Angiomyolipoma With Sarcomatous Transformation and Pulmonary Metastases

We report the case of a 49-year-old woman with a large renal angiomyolipoma that invaded the liver. In some areas, the tumor had the appearance of a typical angiomyolipoma; however, it also had foci where the spindle cells of the lesion showed marked cytologic atypia and mitotic activity, giving it the appearance of a high-grade sarcoma. Immunohistochemical studies demonstrated expression of vimentin, desmin, and muscle-specific actin by the sarcoma cells; these findings were consistent with leiomyosarcoma. A second, small typical angiomyolipoma was also present in the kidney. In addition, the liver exhibited focal nodular hyperplasia. Three weeks after resection of the primary renal tumor, pulmonary metastases were diagnosed by fine-needle aspiration biopsy. This is the first report of a case of angiomyolipoma with sarcomatous transformation and biopsy-proven metastatic disease.

Reliability of Prognostic Models in Malignant Melanoma

Certain histologic and clinical features of malignant melanoma have been shown to be indicators of prognosis, both collectively and individually. Even though the predictive value of these features is well established, long-term survival is occasionally seen in individuals with multiple poor prognostic factors. To further examine this phenomenon, histologic sections from 53 patients with malignant melanoma excised between the years 1977 and 1980 in whom reliable clinical follow-up data were obtained were evaluated for the presence of features associated with a poor prognosis (thickness greater than 1.7 mm, Clark level greater than or equal to III, vertical growth phase, high mitotic index, marked cytologic atypia, minimal tumor inflammatory infiltrate, presence of regression, presence of plasma cells, male sex, age greater than or equal to 45 years, and axial anatomic location). Sixty-eight percent of the patients survived for greater than or equal to 10 years. Of these, 26% had lesions greater than or equal to 1.7 thick. Multivariate discriminant analysis of all features provide a model that was 76% accurate in predicting outcome over a 10-year period. Although the predictive value of these prognostic variables is generally reliable, there is a significant population of long-term survivors in whom prognosis could not be accurately predicted using these features.

Pigmented spindle cell naevus and its variants: distinction from melanoma.

We report seven examples of pigmented spindle cell naevus (PSCN) and variants, emphasizing their histopathologic differentiation from malignant melanoma (CMM). Confusion with CMM may occur because of upward migration (pagetoid spread) of cells, prominent lateral extension of lentiginous melanocytic hyperplasia, and cytological atypia in spindle cell naevi. However, these proliferations are usually associated with a symmetrical and orderly growth pattern, confinement of the pagetoid spread to the lower epidermis, 'maturation' of the dermal component, and lack of marked cytological atypia.

Oral epithelial dysplasia in vitamin B 12 deficiency

Widespread soreness and focal ulceration of the oral mucosa developed in a woman with vitamin B 12 deficiency shortly after hydroxocobalamin therapy had commenced. An oral mucosal biopsy showed disordered epithelial maturation with marked cytologic atypia. However, during the next month of treatment, the patient's oral mucosa became clinically and histologically normal. Pathologists should be aware that vitamin B 12 deficiency may be associated with epithelial changes similar to those associated with premalignancy.

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.

Malignant histiocytosis of Bernese mountain dogs.

A second histiocytic proliferative disorder, which resembled malignant histiocytosis of man, was identified in 13 Bernese mountain dogs. Malignant histiocytosis was clearly distinct from systemic histiocytosis, which was reported earlier in this breed. Eleven cases involved male dogs. Ten dogs occurred in the same family line as the dogs afflicted with systemic histiocytosis. Clinical or radiological evidence of pulmonary involvement was present in nine dogs. Neurological disturbances were present in five dogs. Anemia was observed in five dogs and was associated with prominent erythrophagocytosis in two instances. The clinical course was rapidly progressive. Necropsy examinations revealed that infiltrates were especially frequent in the lungs and hilar lymph nodes. Other lymph nodes, liver, spleen, and central nervous system were also frequently involved. Evidence for primary pulmonary involvement was present in seven dogs. The original diagnosis in seven cases was large cell anaplastic carcinoma of the lung by light microscopy only. The infiltrates were composed of large, pleomorphic, phagocytic mononuclear cells and multinucleated giant cells which also manifested marked cytological atypia and numerous, frequently bizarre, mitotic figures. Ultrastructural studies and the immunohistochemical demonstration of lysozyme and alpha 1-antitrypsin in the tumor cells in the majority of cases were consistent with a macrophage origin.