Alfred Beham

Myxofibrosarcoma. Clinicopathologic analysis of 75 cases with emphasis on the low grade variant

Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly patients. We analysed the clinicopathologic features in a series of 75 patients. All patients were adults (range, 22-91 years; median, 66 years) with an approximately equal incidence in men and women. Thirty-five tumors arose in the lower and 25 in the upper extremities, nine on the trunk, two each in the retroperitoneum and the head and neck region, and one each in the pelvis and penis. Forty-eight cases (69.5%) were located in dermal or subcutaneous tissues. Distinctive histologic features included the following: a commonly nodular growth pattern; a myxoid matrix containing elongated, curvilinear capillaries; and fusiform, round or stellate tumor cells with indistinct cell margins, slightly eosinophilic cytoplasm, and hyperchromatic atypical nuclei. These lesions varied from a hypocellular, mainly myxoid, and purely spindle-cell appearance (low-grade neoplasms) to high-grade, pleomorphic (malignant fibrous histiocytoma-like) lesions with multinucleated giant cells, high mitotic activity, and areas of necrosis. Immunohistochemistry in 44 cases revealed only vimentin and occasional actin positivity. Ultrastructurally, tumor cells had a fibroblastic phenotype. DNA flow cytometry and proliferation analysis showed an association between aneuploidy and histologic grade. An average follow-up of 45 months (range, 5-300 months) in 60 cases has revealed local recurrence in 33 cases (54%). Thirteen patients developed metastases, and 13 tumor-related deaths occurred. A short interval to first local recurrence was associated with poor clinical outcome. The rate of local recurrence was independent of histologic grade, but only intermediate and high-grade neoplasms metastasized. The depth of the primary lesion did not influence the incidence of local recurrence. However, in deep-seated neoplasms, the incidence of metastases was higher and the percentage of tumor-related deaths was twice as high as in superficially located lesions, reflecting the fact that deep-seated lesions tended to be higher-grade, larger tumors. Myxofibrosarcoma tends to become progressively higher grade in recurrences, as demonstrated in five cases in our series. The poorly recognized low-grade myxofibrosarcoma is emphasized, as proper diagnosis and treatment and scrupulous follow-up are mandatory to avoid local recurrence and gradual tumor progression to a higher-grade neoplasm that may then metastasize.

Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases.

Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/ neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was > 5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.

Fibrosarcomatous (high-grade) dermatofibrosarcoma protuberans: Clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance

The fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) represents an uncommon form of DFSP, in which the prognostic influence of the fibrosarcomatous component is still debated. We analyzed the clinicopathologic and immunohistochemical features in a series of 41 patients. Patient age ranged from 8 to 87 years (median, 48 years), and 19 patients were female. Twenty five lesions were seen on the trunk, 6 on the upper limbs, and 4 on the lower limbs, and five neoplasms were located in the head/neck region; in one case, exact anatomic site was unknown. Twenty seven tumors involved purely dermal and subcutaneous tissues, in 10 cases, deeper structures were also involved, 1 case arose in the breast, and, in 3 cases, it was impossible to define exact depth of the lesion. Preoperative duration ranged from 1 month to 60 years (median, 3 years). Twenty six tumors were excised locally with clear margins, 7 were treated by wide excision, 3 by incomplete excision, and, in 4 patients, the lesion was shelled out. In one case, exact treatment was unknown. In addition, radiotherapy was administered in three cases and chemotherapy in one case. Histologically, the lesions showed areas of typical, low-grade DFSP adjacent to fibrosarcomatous areas. In four cases, a previously ordinary DFSP recurred as pure fibrosarcoma, in two cases, local recurrence of FS-DFSP showed features of ordinary DFSP. Fibrosarcomatous change was more common in the primary (de novo) lesions than in recurrent lesions (3.6:1). Proportion of fibrosarcoma varied between < 30% in 6 cases to > 70% of tumor tissue in 21 cases. An abrupt transition between both components was seen in 19 cases. The fibrosarcomatous component showed focal necrosis in seven cases and showed a higher mitotic rate in comparison with ordinary DFSP areas (mean, 13.4 versus 2.3 mitoses in 10 high-power fields). Additional histologic features included progression to pleomorphic sarcoma in 2 recurrent cases, melanin-pigmented cells (Bednar FS-DFSP) in 1 case, focal myxoid change in 13 cases, plaque or keloidlike hyalinization in 3 cases, and myoid bundles and nodules in 9 cases. Immunohistochemically, tumor cells in DFSP areas stained positively for CD34, whereas, in FS-DFSP areas, only 15 out 33 cases were positive for CD34. Follow-up in 34 of 41 patients (mean, 90 months; median, 36 months) revealed local recurrence in 20 patients (58%) (recurrence occurred in 5 patients on two or more occasions). Metastases (5 lung, 1 bone, and 1 soft tissue) were seen in 5 patients (14.7%), and 2 patients have died of tumor to date (5.8%). Necrosis, high mitotic rate (> 10 mitoses per 10 high-power fields), and presence of pleomorphic areas in FS-DFSP tended to be related with poor clinical outcome, but no statistically significant association was detected. Fibrosarcomatous change in DFSP represents a form of tumor progression in DFSP and is associated with a significantly more aggressive clinical course than in ordinary DFSP, indicating a possible need for treatment intensification in such cases.

Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas.

Dedifferentiated liposarcoma is uncommon, and only a small number of cases have been documented. We describe the clinicopathologic features in a series of 32 cases. All patients were adults (age range, 37–83 years; median, 67 years); 20 were men and 12 were women. Commonest site was the retroperitoneum (fifteen cases); six cases arose in the limbs, four in the paratesticular region, three in the peritoneal cavity, two on the trunk, and one each in the buttock and larynx. One primary tumor was subcutaneous. Thirty tumors arose de novo (i.e., combined with well-differentiated tumor in the primary lesion), while two developed in recurrences of a previously well-differentiated liposarcoma. The well-differentiated component was most often lipoma-like and typically there was a histologically abrupt transition to spindle celled nonlipogenic tumor. The dedifferentiated component most often resembled either storiform “malignant fibrous histiocytoma” (“MFH”) with limited pleomorphism or myxofibrosarcoma (myxoid “MFH”); the latter pattern is rarely otherwise seen in the retroperitoneum. A small number of cases showed appearances reminiscent of myxoid embryonal rhabdomyosarcoma. An unusual feature in three cases was the occurrence of a discontinuous micronodular pattern of dedifferentiation. Average follow-up of 5.6 years (range, 3 months to 33 years) in 27 cases have revealed local recurrence in 14 patients and systemic metastases in only four patients. The primary sites of the metastasising cases were upper back, thigh, retroperitoneum, and paratesticular region. There have been only seven tumor-related deaths. Good prognosis in de novo dedifferentiated liposarcomas seems unrelated to the extent or morphologic pattern of dedifferentiation. However, high mitotic activity in the dedifferentiated component was associated with a more aggressive clinical course. Our study underlines that dedifferentiation in peripherally located or even subcutaneous liposarcomas does occur, albeit rarely, and that dedifferentiated liposarcomas of the limbs may metastasize. The results suggest that dedifferentiated liposarcomas, as a subgroup among the “MFH-like” sarcomas, have a better prognosis than pleomorphic sarcomas as a whole.

Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm.

We report eight cases of epithelioid angiosarcoma arising in deep, usually intramuscular soft tissue. All the patients were men (mean age, 58). All the lesions arose in a limb or limb girdle. Cardinal morphologic features were the diffuse, sheetlike growth pattern, with only focally apparent vascular differentiation, and epithelioid tumor cells with a degree of intracytoplasmic vacuolation/lumen formation. Immunohistochemically, all eight cases coex-pressed keratin as well as endothelial markers. In three cases, endothelial differentiation was confirmed ultra-structurally. Clinically, deep-seated epithelioid angiosarcomas are high-grade neoplasms that rapidly develop metastases. These findings expand the range of recognized epithelioid endothelial tumors and provide further evidence of keratin expression by such lesions. The presence of intracytoplasmic lumina/vacuoles (sometimes containing red blood cells) combined with the characteristic reticulin pattern and striking positivity for Factor VIII-RAg provide the clearest means of distinction from an epithelial metastasis.

‘Eosinophilic Fungal Rhinosinusitis’: A Common Disorder in Europe?

Objectives/Hypothesis The traditional criteria for the diagnosis of allergic fungal sinusitis include chronic rhinosinusitis, “allergic mucin” (mucus containing clusters of eosinophils), and detection of fungi by means of histological examination or culture. In 1999, a group of Mayo Clinic researchers, with a novel method of mucus collection and fungal culturing technique, were able to find fungi in 96% of patients with chronic rhinosinusitis. Immunoglobulin E–mediated hypersensitivity to fungal allergens was not evident in the majority of their patients. Because the presence of eosinophils in the allergic mucin, not a type I hypersensitivity, is probably the common denominator in the pathophysiology of allergic fungal sinusitis, the Mayo Clinic group proposed a change in terminology from allergic fungal sinusitis to eosinophilic fungal rhinosinusitis. Using new techniques of culturing fungi from nasal secretion, as well as preservation and histological examination of mucus, we investigated the incidence of “eosinophilic fungal rhinosinusitis” in our patient population.

Nasopharyngeal angiofibroma: true neoplasm or vascular malformation?

Summary: Nasopharyngeal angiofibromas (NA) are rare tumor‐like lesions characterized by architecturally irregular vessels set in a fibrous stroma. The unique morphology, the strong predilection for male adolescents, and the uncertainty about its etiology contributes to significant confusion regarding the classification of NA, which still has not been solved today. Based on immunohistochemical and electron microscopic examinations, we demonstrate in detail the various unusual vascular architectural features of NA. They represent discontinuous vascular basal laminae, focal lack of pericytes, and pronounced irregularity of the smooth muscle layers. In thick smooth muscle layers and pads, the orientation of muscle cells is frequently disturbed, and the individual cells differ in size and shape. Occasionally, the muscle layers disperse peripherally into individual cells, creating the impression of vessel‐independent smooth muscle cells within the stroma. The summation of all morphological irregularities demonstrated in this paper allows the conclusion that NA represent vascular malformations.

Keratoacanthoma: a clinically distinct variant of well differentiated squamous cell carcinoma.

Summary Keratoacanthomas are distinct skin lesions that occur most often as solitary tumors in sun-exposed areas in elderly, fair-skinned patients. Clinically, these tumors are characterized by a rapid onset and regression within months. Keratoacanthomas display distinct histological features including a keratin-filled crater lined by a proliferating squamous epithelium. Cytologically, there may be overlap with classical well differentiated squamous cell carcinoma. Rarely, otherwise typical keratoacanthomas show intravascular and perineural invasion and lymph node metastases. Keratoacanthomas should, therefore, be considered to be a clinically distinct variant of well differentiated squamous cell carcinoma capable of spontaneous regression. This view is supported by their common etiology, occasional concurrent occurrence, and a multitude of studies revealing no substantial differences between these two lesions. Regression is immunologically mediated and activated by a variety of molecular mechanisms. Considering the common nature of keratoacanthomas and well differentiated squamous cell carcinomas, and the lack of any features predicting prognosis, surgical excision of keratoacanthoma is advisable.

Solitary myofibroma in adults: clinicopathological analysis of a series

Solitary myofibroma is a recently described, benign neoplasm of superficial soft tissue, which represents the adult counterpart of infantile myofibromatosis and is poorly recognized. Eleven new cases are presented herein. The patients were mostly adults with ages ranging from 13–64 years. They presented with a solitary, usually painless nodule of variable duration in the skin or oral cavity. Histologically, each lesion had a biphasic pattern with spindle cells forming fascicular or whorled areas and rounded, more primitive cells arranged around small vessels, forming haemangioperi‐cytoma‐like areas. The characteristic zonation of infantile myofibromatosis was often less marked in adult lesions and there was a haphazard arrangement of the fascicular and pericytic areas in some cases. Hyalinization, especially of the peripheral spindle‐celled areas, was frequent. Immunohistochemically, the spindle cells were desmin negative but muscle actin (HHF‐35 and IA4) positive. The rounded cells were both desmin and actin negative. Electronmicroscopy confirmed the myofibroblastic/fibroblastic nature of tumour cells in two cases. Although vascular invasion was seen in two cases, solitary adult‐type myofibroma pursues a benign clinical course.

Intramuscular angioma: a clinicopathological analysis of 74 cases.

We have studied 74 benign intramuscular angiomas in order to try and correlate clinical behaviour with histological appearances. The purpose was to find means of predicting those which would recur. Mean age at presentation was 17.6 years and 85% of the cases presented before age 30. The male: female ratio was 1.4:1. Anatomical distribution was 32% lower limb. 27% head/neck, 24% upper limb and 17% trunk. Reliable histological subclassification proved impossible since almost all lesions were of mixed type, albeit often with a single predominant vessel type—of which venous (42%) was the most common. Over 90% of the lesions contained a variably prominent adipocytic component. More than 50% of patients suffered local recurrence. Neither predominant vessel type nor anatomical localization correlated with recurrence, which was always due to incomplete excision.