Antonio G. Nascimento

Desmoplastic small round cell tumor: A clinicopathologic, immunohistochemical, and molecular study of 32 tumors

Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young male patients and is characterized by a reciprocal translocation t(11;22)(p13;q12) associated with the EWS-WT1 gene fusion transcript. Clinical, histopathologic, immunohistochemical, and molecular genetics features were reviewed for 32 tumors. There were 29 male and three female patients, with ages from 6 to 54 years (mean, 25 years). The main clinical signs and symptoms included abdominal pain (eight patients), weight loss (five patients), and presence of umbilical hernia (four patients). Two tumors primarily involved the ethmoid sinus and the soft tissues of the scalp; the other tumors (mean size, 10 cm) involved the abdominal cavity (88%). One patient presented initially with an axillary lymph node metastasis. Generally, all tumors showed the typical histologic findings of variably sized clusters of small, round, or spindled cells lying in a desmoplastic stroma. The neoplastic cells in formalin-fixed, paraffin-embedded tissue sections were positive for desmin (dot pattern) (81% of the cases), WT1 (91%), keratin (87%), neuron-specific enolase (84%), CD99 (23%), and actin (3%). The EWS-WT1 gene fusion transcript was detected in 29 of 30 tumors. One tumor with typical clinicopathologic and immunohistochemical features did not show the gene fusion. Follow-up for 27 patients showed that 19 patients (70%) died of uncontrolled, local, or widespread metastatic disease 3–46 months (mean, 20 months) after diagnosis, and eight patients were alive with known evidence of disease. Occasionally, desmoplastic small round cell tumor lacks the classic clinical, histologic, and immunohistochemical features. This study emphasizes the utility of analysis of the EWS-WT1 gene fusion transcript, which was performed on paraffin-embedded tissues, to confirm the diagnosis.

Inflammatory pseudotumors of the lung

BACKGROUND Inflammatory pseudotumors of the lung are rare and often present a dilemma for the surgeon at time of operation. We reviewed our experience with patients who have this unusual pathology. METHODS Between February 1946 and September 1993, 56,400 general thoracic surgical procedures were performed at the Mayo Clinic. Twenty-three patients (0.04%) had resection of an inflammatory pseudotumor of the lung. There were 12 women and 11 men. Median age was 47 years (range, 5 to 77 years). Six patients (26%) were less than 18 years old. All pathologic specimens were re-reviewed, and the diagnosis of inflammatory pseudotumor was confirmed. Eighteen patients (78%) were symptomatic which included cough in 12, weight loss in 4, fever in 4, and fatigue in 4. Four patients had prior incomplete resections performed elsewhere and underwent re-resection because of growth of residual pseudotumor. Wedge excision was performed in 7 patients, lobectomy in 6, pneumonectomy in 6, chest wall resection in 2, segmentectomy in 1, and bilobectomy in 1. Complete resection was accomplished in 18 patients (78%). Median tumor size was 4.0 cm (range, 1 to 15 cm). There were no operative deaths. Follow-up was complete in all patients and ranged from 3 to 27 years (median, 9 years). RESULTS Overall 5-year survival was 91%. Nineteen patients are currently alive. Cause of death in the remaining 4 patients was unrelated to pseudotumor. The pseudotumor recurred in 3 of the 5 patients who had incomplete resection; 2 have had subsequent complete excision with no evidence of recurrence 8 and 9 years later. CONCLUSIONS We conclude that inflammatory pseudotumors of the lung are rare. They often occur in children, can grow to a large size, and are often locally invasive, requiring significant pulmonary resection. Complete resection, when possible, is safe and leads to excellent survival. Pseudotumors, which recur, should be re-resected.

Adenoid cystic carcinoma of salivary glands. A study of 61 cases with clinicopathologic correlation

Sixty‐one cases of adenoid cystic carcinoma of the head and neck region, excluding the ear canal, lacrimal glands, larynx, esophagus, and trachea, were studied, and their different clinicopathologic aspects were analyzed. Adenoid cystic carcinoma occurred more commonly in the minor salivary glands; the palate was affected in 31% of the cases. The fifth decade of life was the age at which patients were most commonly affected, and there was a slight predominance of white women. In most patients a mass was the main complaint; in 63% the duration of symptoms was 1 year or less. Forty‐one patients had Stages 3 or 4 disease when first seen, and 51.7% of the patients died of disease, with a mean survival period of 35.4 months. Three basic patterns of growth, solid, cribriform, and tubular, were identified in the histopathologic examination of the cases. Other pathologic aspects analyzed were cellular pleomorphism, mitotic activity, necrosis, vascular invasion, and perineural infiltration. The study revealed a positive correlation between location of the tumor, clinical staging, duration of symptoms, and histologic pattern of growth with the prognosis of the lesion. Tumors located in the minor salivary glands, those in which the duration of symptoms was less than 1 year, and those that showed advanced clinical staging and a predominantly solid pattern of growth had an extremely poor prognosis. Surgery is the treatment of choice of adenoid cystic carcinoma, and microscopically free surgical lines of resection must be obtained. Radiation therapy, although not curative, plays an important role in prolonging survival.

Clear Cell Sarcoma of Soft Tissues: Mayo Clinic Experience With 35 Cases

Thirty-five cases of clear cell sarcoma of soft tissues were studied to determine the clinical or morphologic features that are important in predicting prognosis. Tumors occurred most commonly in the extremities, and the majority of the patients were young women. Surgery was the elected treatment in every case. Five patients experienced local recurrences, and metastases developed in 22. Fifty-four percent of the patients died of tumor, 11% are alive with disease, and the remaining 34% are alive and well; the average survival for each group was 67 months, 113 months, and 103.5 months, respectively. This sarcoma is characterized by small clusters of polygonal to spindle cells featuring clear to slightly basophilic cytoplasm and vesicular nuclei with prominent nucleoli. The clusters are separated by delicate fibrous septa. In a deletion, clear cell sarcoma has low mitotic activity, little or no necrosis, and mild nuclear pleomorphism. Tumor size and the presence of necrosis are statistically significant predictors of prognosis. All 12 patients with tumors measuring >5 cm died of disease or are alive with disease. Eleven of the 20 patients with tumors measuring <5 cm are alive with no evidence of disease. Tumor necrosis was present in 10 cases; eight of these patients died of disease and one is alive with disseminated metastases.

Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature

Primary sarcomas of the breast are extremely rare, with less than 0.1% of all malignant tumours of the breast. Mayo Clinic Surgical Pathology database was searched for all breast sarcoma from 1910 to 2000. Pathology reports and slides were reviewed and tumour types were determined. Metaplastic carcinomas and phyllodes tumours were excluded. There were 25 women ranging in age 24–81 years (mean 45 years). All but one patient presented with a palpable lump. Mastectomy was performed in 19 patients and lumpectomy in five patients. Histopathological diagnoses were fibrosarcoma (six), angiosarcoma (six), pleomorphic sarcoma (six), leiomyosarcoma (two), myxofibrosarcoma (three), hemangiopericytoma (one) and osteosarcoma (one). Tumour size ranged from 0.3 to 12 cm (mean 5.7). Low-grade lesions were observed in 10 cases and high-grade in 15. Overall, mean follow-up was 10.5 years. Local recurrence was observed in 11 patients and ranged from 2 to 36 months (mean 15 m), while distant metastasis was observed in 10 patients (40%) affecting lungs, bones, liver, spleen, and skin. Of the 25 patients, 12 have died of disease and six of other causes. Five-year overall (OS) and cause-specific survival (CSS) were 66 and 70%, respectively. OS and DFS at 5 years were 91% for tumours ⩽5 cm and 50% for tumours >5 cm. Tumour size was significantly associated with OS (risk ratio=1.3 per 1 cm increase; 95% CI, 1.02–1.7; P=0.036). There was no significant difference in OS or CSS between low- and high-grade lesions. In this series, tumour size was a more valuable prognostic factor than tumour grade.

The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningioma and solitary fibrous tumor of meninges.

Despite controversy regarding its histogenesis, meningeal hemangiopericytoma (HPC) is a well-defined clinicopathologic entity exhibiting high rates of recurrence and late extracranial metastasis. It must be distinguished from several benign neoplasms, particularly fibrous meningioma (FM) and solitary fibrous tumor (SFT). To determine the immunoprofile of HPC, we studied 27 meningeal examples, including 13 low-grade and 14 high-grade tumors. For comparison, 20 FMs and eight SFTs of the meninges were also evaluated. The immunotype of HPC included vimentin (85%), factor XIIIa (78%) in individual scattered cells, Leu-7 (70%), and CD34 (33%) in a weak, patchy pattern. Focal desmin and cytokeratin positivity was only occasionally encountered (20% each). The SFT shared a similar immunophenotype, except that CD34 expression (100%) was characteristically strong and diffuse. The FM characteristically expressed epithelial membrane antibody (EMA) (80%) and S-100 protein (80%); CD34 reactivity (60%) was patchy and weak. Both within and among all three tumor types, MIB-1 labeling indices varied widely. Specifically, they were unrelated to tumor grade in HPC. Significant reactivity for p53 protein was detected in 52% of HPCs, 17% of SFTs, and 5% of FMs. Meningeal HPC exhibits a distinct antigenic profile, one enabling the exclusion of other entities in nearly all cases. The rare expression of desmin or cytokeratin in HPC suggests either the occurrence of divergent differentiation or, less likely, the possibility that its distinctive morphology is but a phenotype shared by several types of meningeal sarcoma.

The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.

Low‐grade fibromyxoid sarcoma (LGFMS) is a variant of fibrosarcoma that was recognized as a distinct tumor entity only quite recently. We previously described a translocation, t(7;16)(q33;p11), that resulted in a fusion of the FUS and CREB3L2 (also known as BBF2H7) genes in two soft tissue tumors that fulfilled morphologic criteria for LGFMS. To delineate the spectrum of tumors that may harbor the FUS/CREB3L2 gene, we selected 45 low‐grade spindle cell sarcomas for reverse transcriptase polymerase chain reaction (RT‐PCR) and/or fluorescence in situ hybridization (FISH) analyses; none of these tumors had originally been diagnosed as LGFMS. Furthermore, also included were two benign soft tissue tumors and nine high‐grade sarcomas with supernumerary ring chromosomes or 7q3 rearrangement and three tumors diagnosed as LGFMS prior to the genetic analysis. Of the 59 tumors analyzed, 12 were FUS/CREB3L2‐positive, all of which were diagnosed at histopathologic re‐examination as being LGFMS, of both the classical subtype and the subtype with giant collagen rosettes. The breakpoints in the fusion transcripts were always in exons 6 or 7 of FUS and exon 5 of CREB3L2. The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT‐PCR or FISH analysis may be useful for the differential diagnosis.

Infantile Hemangiopericytoma Versus Infantile Myofibromatosis Study of a Series Suggesting a Continuous Spectrum of Infantile Myofibroblastic Lesions

The clinicopathologic features of 11 tumors, originally diagnosed as infantile hemangiopericytomas and with a spectrum of morphologic findings, are described. The age of the patients ranged from 6 days to 7 years; seven patients were younger than 1 year (mean, 2.25 years; median, 10 months); six were boys and five were girls. Three neoplasms were situated in skin or subcutis and seven in deep soft tissue; in one case the depth was unstated. Seven lesions arose in the lower limbs, and one each in the lumbar region, clitoris, chest wall, and soft tissue of the zygomatic region. One patient later was found to have two additional dermal tumors, one each on the anterior abdominal wall and the chest wall. Follow-up information in eight patients revealed local recurrence 12 years later in one case only. Histologically, all tumors showed distinctive features of infantile hemangiopericytoma, including immature cytology, multilobulated growth pattern, focal necrosis, and mitotic activity in varying degrees. Vascular invasion was noted in seven cases. Additionally, a second tumor cell component, composed of spindleshaped myofibroblastic cells forming fascicles and micronodules, was evident at least focally. Both the spindle cells and more primitive round cells were positive for α-smooth muscle actin. Both cellular components showed a haphazard zoning arrangement. We discuss the clinicopathologic similarities between infantile hemangiopericytoma and infantile myofibromatosis and point out the differences between infantile and adult hemangiopericytoma. Our study suggests that there exists a broad spectrum of benign infantile myofibroblastic lesions containing an immature-appearing cellular component with a distinctive, hemangiopericytoma-like vascular pattern. Infantile myofibromatosis and so-called infantile hemangiopericytoma almost certainly represent different stages of maturation of the same (single) entity.

Local control of extra-abdominal desmoid tumors.

We analyzed the records and histopathological specimens of fifty patients who had had a previously untreated desmoid tumor. The patients were followed for at least two years (average, forty-eight months). Three patients had a biopsy and were managed with observation only, and three patients had radiation therapy only. Of the remaining forty-four patients, thirty-four were managed with an operation and ten, with an operation and radiation therapy. In the group that was managed operatively without radiation therapy, the resection was wide in thirteen patients, marginal in nineteen, and intralesional in two. At the most recent follow-up examination, there had been no local recurrence in eleven of the patients who had had a wide resection, ten of the patients who had had a marginal resection, and one of the patients who had had an intralesional resection. Thus, twenty-two (65 per cent) of the thirty-four patients had no local recurrence at the time of the latest follow-up. In the group of ten patients who had been managed with an operation and radiation therapy, eight had no local recurrence: the two who had had a wide resection, three of the four who had had a marginal resection, and three of the four who had had an intralesional resection. None of the fifty patients died of the disease.

Primary giant cell tumor of soft tissues: a study of 22 cases.

Twenty-two cases of giant cell tumor of soft tissues (GCT-ST) identified in the Mayo Clinic files and the consultation files of two of the authors (A.G.N., C.D.M.F.) were analyzed clinicopathologically. Age at presentation ranged from 5 to 80 years (median, 43 years), and there was no sex predilection (12 male, 10 female). Duration of symptoms ranged from 2 to 12 months (median, 4.5 months), and a painless growing mass was the most common complaint. The lower limbs were the most frequent location (50%), followed by the trunk (31.8%) and the upper limbs (13.6%). The size of the tumors ranged from 1 to 10 cm, and they tended to be superficial (86.4%), forming well-circumscribed (72.7%), multinodular (86.4%) masses. Histologically, all tumors consisted of a mixture of mononuclear cells showing vesicular, round to oval nuclei and osteoclastlike, multinucleated giant cells distributed uniformly throughout the tumors. Foci of stromal hemorrhage were observed in 11 tumors (50%); nine tumors (40.1%) showed metaplastic bone formation and six (27.2%) showed aneurysmal bone cystlike areas. Necrosis was absent in all but one tumor. Mitotic figures were present in all but one tumor, ranging from two to more than 30 mitoses per 10 high-power fields (HPFs; median, 9.5 mitoses per 10 HPFs) and were typical in aspect. Vascular invasion was identified in seven tumors (31.8%), and none of the tumors showed marked cellular atypia or pleomorphism. The tumors were treated surgically, and follow-up information was available for 16 patients (duration of follow-up, 2 to 130 months; median, 51 months). Only one of the 16 patients (6.2%) had local recurrence and lung metastases; this patient died of the tumor. In conclusion, GCT-ST occurs as a primary soft-tissue neoplasm and is identical clinically and morphologically to giant cell tumor of bone. Provided that GCT-ST is treated adequately by complete excision, a benign clinical course is expected because episodes of distant metastasis and tumor-associated death seem to be exceedingly rare.