[Clinicopathologic features of atypical spindle cell lipomatous tumor].

Objective: To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Methods: Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. Results: All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. Conclusions: ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.

Pseudomyogenic hemangioendothelioma: report of an additional case with aggressive clinical course.

: Pseudomyogenic hemangioendothelioma is a recently described vascular tumor that occurs predominantly in the distal extremities of young adults. Because of multifocal presentation, epithelioid morphology, and strong cytokeratin expression, the tumor was frequently misdiagnosed as epithelioid sarcoma. However, substantial immunohistochemical studies revealed an endothelial nature. It has been currently considered a tumor of intermediate malignancy with frequent local recurrence but low risk of distant metastasis. In this report, we describe a case of pseudomyogenic hemangioendothelioma occurring in a 22-year-old man who presented with multifocal disease in the lower extremity and developed bilateral pulmonary metastases within a short period.

Histiocyte-rich rhabdomyoblastic tumor: a report of two cases and a review of the differential diagnoses.

Histiocyte-rich rhabdomyoblastic tumor is a recently described skeletal muscle neoplasm of uncertain malignant potential, characterized by slow growth, a fibrous capsule containing peripheral lymphoid aggregates, spindle-to-epithelioid cells with a rhabdomyoblastic immunophenotype, and a dense histiocytic infiltrate. It most commonly arises within the muscles of the lower legs and trunk in young-to-middle-aged men, and initial reports suggest indolent behavior. In this paper, we present two additional cases of histiocyte-rich rhabdomyoblastic tumor with similar clinicopathologic features and discuss the differential diagnosis including its overlap with inflammatory leiomyosarcoma.

A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors.

Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging. Using a series of tissue microarrays that contain 245 cases of leiomyosarcomas (102 gynecologic) with survival data, and 49 cases of uterine leiomyoma, we examined the ability of selected immune-markers (estrogen receptor (ER) and WT1) to distinguish between leiomyosarcomas of gynecologic and nongynecologic origin. In addition, we examined whether immunostains for p16, p53 and Ki-67 could distinguish between malignant and benign gynecologic smooth muscle tumors. ER nuclear positivity was observed in 3 and 50% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). Nuclear WT1 positivity was seen in 0 and 8% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). 87% of primary gynecologic leiomyosarcomas and 2% of uterine leiomyomas showed diffuse (>or=50% of cells) p16 staining (P<0.001). 23% of gynecologic leiomyosarcomas showed p53 immunopositivity (>or=50% of cells) whereas none of the leiomyomas were positive for p53 (P<0.001). 65% of the gynecologic leiomyosarcomas and 0% of the leiomyomas exhibited >10% Ki-67 proliferation index (P<0.001). Diffuse p16 and p53 immunopositivity and high Ki-67 proliferation index, singly or in combination, yielded an overall sensitivity of 92% and specificity of 98% for distinguishing between gynecologic leiomyosarcomas and leiomyomas and can be used as indicators of malignancy for gynecologic smooth muscle tumors. Although ER positivity can be used to support the gynecologic origin of a leiomyosarcomas, nuclear WT1 immunostaining is of little use.

Neurofibromatosis type 2: optic nerve sheath meningioma in one orbit, intramuscular schwannoma in the other.

A highly unusual patient with neurofibromatosis type 2 (NF2) presenting with simultaneous bilateral orbital tumors is described. A 12-year-old girl with a family history of NF2 was examined because of bilateral proptosis. Visual acuities were light perception RE and 20/40 LE. Magnetic resonance imaging studies showed bilateral cerebellopontine angle tumors, a tumor surrounding the right intraorbital optic nerve, and a large left lateral orbital mass mixed with the lateral rectus muscle. The histopathological diagnoses following incisional biopsies were right optic nerve sheath meningioma and left intramuscular schwannoma. The left-sided orbital schwannoma and the right-sided vestibular schwannoma were treated with fractionated stereotactic radiotherapy. This patient enlarges the spectrum of clinical presentations that can be encountered at young age in patients with NF2.

Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic tool in the classification of myxoid soft tissue tumors.

BACKGROUND: Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological similarities, they differ considerably in their biological behaviour. Intramuscular / cellular myxoma rarely shows signs of recurrence and never metastasizes, in contrast to myxofibrosarcoma that tends to recur more aggressively and to metastasize haematologically. Therefore, it is of great importance to distinguish these lesions - evaluation of GNAS mutation status could be of tremendous help. METHODS: We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years). Immunohistochemistry was performed as well as next generation sequencing. Ten cases were located in the lower extremities and three cases were located in the upper extremities. Two lesions were initially misdiagnosed as a low-grade myxofibrosarcoma. RESULTS: Performing next generation sequencing 12 out of 13 specimens showed a GNAS mutation. CONCLUSIONS: Our findings demonstrate that GNAS mutations are more common in intramuscular / cellular myxomas, than had been reported in literature in the past. Next generation sequencing for determining GNAS mutation status on small biopsies or diagnostically challenging cases facilitates the diagnosis of intramuscular / cellular myxoma and separates this tumor entity from its mimics.

Penile myointimoma in children and adolescents: a clinicopathologic study of 5 cases supporting a distinct entity.

Penile myointimoma is a rare benign myointimal proliferation occurring exclusively within the corpus spongiosum of the glans penis and is most commonly described in adult patients. To date, there is only one reported series of 10 penile myointimomas plus one case report, representing a total of 8 adults and 3 children/adolescents. We report 5 penile myointimomas occurring in 5 patients less than 18 years of age (age range 4 to 15 y). All patients presented with a mass lesion on the glans penis ranging in size from 0.4 to 1.8 cm. All 5 lesions had the classic morphologic appearance: myointimal proliferation of the preexisting vascular spaces of the corpus spongiosum, creating a multinodular/plexiform architecture. Immunohistochemically, all stained cases showed strong cytoplasmic immunoreactivity for smooth muscle actin in the lesional cells and a collarette of native smooth muscle highlighted by desmin. None of the lesions appeared completely excised, but all 5 patients were clinically free of disease at last clinical follow-up (2 to 45 mo). In summary, we report only the second series of this distinctive, relatively rare myointimal proliferation within the corpus spongiosum of the glans penis, expand the number of published cases occurring in the pediatric/adolescent population, and confirm the benign clinical course after a marginal or incomplete excision.

[Pseudomyogenic hemangioendothelioma in the upper limb: A case report and literature review]. / Hemangioendotelioma pseudomiogénico en miembro superior: descripción de un caso y revisión de la literatura.

Pseudomyogenic hemangioendothelioma, also called epithelioid sarcoma-like hemangioendothelioma, is a rare, vascular neoplasm usually with indolent behaviour. It was introduced in the latest World Health Organization (WHO) Classification of Tumours of Soft Tissue. We report a case of a 45 year-old patient presenting with a localized, palpable and slightly painful lesion in the left arm. Histologically it consisted of fascicles of spindle and epithelioid cells with ample eosinophilic cytoplasm, without nuclear pleomorphism or significant mitotic activity. Tumour cells showed diffuse expression for cytokeratin AE1/AE3, CD31 and FLI1, intact expression for INI1 and negativity for CD34. We describe the clinical, histological, molecular and immunohistochemical features of pseudomyogenic hemangioendothelioma and review the pertinent literature.

Chemoradiotherapy for Solitary Skeletal Muscle Metastasis from Oesophageal Cancer: Case Report and Brief Literature Review.

BACKGROUND: The incidence of skeletal muscle metastasis from oesophageal cancer is very low, and the treatment strategy has not been established. CASE REPORT: A 77-year-old man underwent oesophagectomy following neoadjuvant chemotherapy for oesophageal squamous cell carcinoma (CT-pT3 N0 M0, CT-pStage II). Fourteen months after surgery, he became aware of a subcutaneous tumour in his left forearm. Computed tomography and fluorodeoxyglucose positron-emission tomography revealed a 65×75 mm intramuscular nodular lesion with a standardized uptake value of 8.5. Further examination by biopsy strongly suggested this was a solitary metastasis from oesophageal cancer. The patient received chemoradiotherapy with two cycles of 5-fluorouracil combined with cisplatin and radiation. Clinical complete response was confirmed by imaging 7 months after chemoradiation and no recurrence has occurred at 20 months since chemoradiation. CONCLUSION: Radiotherapy or chemoradiotherapy can be an alternative locoregional therapy to surgery for solitary skeletal muscle metastasis.

Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.

Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery. One chest wall soft tissue tumor in a 3-month-old girl case showed a SRF-C3orf62 fusion, while the other, a forearm lesion in an 8-year-old girl, showed a SRF-RELA fusion. Further screening of 42 cellular examples of myofibroma/myopericytoma by fluorescence in situ hybridization identified additional 8 cases with recurrent SRF gene rearrangements, 6 of them showing identical SRF-RELA fusions. The cohort was composed of 7 females and 3 males, with a wide age range of 3 months to 63 years (mean=17). All tumors showed a densely packed growth of oval to spindle cells with fibrillary eosinophilic cytoplasm, arranged either in intersecting fascicles or with a distinct nested pattern around a rich vascular network. Despite the dense cellularity and variable mitotic activity none of the lesions displayed nuclear pleomorphism or necrosis. All tumors showed coexpression for SMA and desmin, in most cases with a strong and diffuse pattern of staining, while myogenin was consistently negative. No distant metastases were seen in the few cases with follow-up information. A control group of 34 well-characterized myofibroblastic and perivascular tumors, including 10 typical myofibromas and 3 myopericytomas, were also investigated for SRF gene abnormalities by fluorescence in situ hybridization and were negative. In summary, we report a subset of cellular variants of myofibroma and myopericytoma showing a smooth muscle-like immunophenotype and harboring recurrent SRF-RELA gene fusions, which mimic sarcomas with myogenic differentiation.

Rhabdomyosarcoma: molecular diagnostics of patients classified by morphology and immunohistochemistry with emphasis on bone marrow and purged peripheral blood progenitor cells involvement.

Two histologically distinct subtypes of rhabdomyosarcomas (RMS), embryonal and alveolar, are different in many aspects, such as age distribution, primary site, and clinical outcome. We analyzed a group of 30 patients with RMS. The aim was to broaden the spectrum of diagnostic tools in evaluating the primary tumors, their recurrences and/or metastases, and to extend the diagnostic boundary to bone marrow and purged peripheral progenitor blood cell samples. We have performed the RT-PCR assay to analyze RMS for the presence of expression of MyoD1 gene and for the presence of chimeric transcripts PAX3/FKHR or PAX7/FKHR. MyoD1 gene expression was found in all 30 patients in samples from primary tumors. The chimeric transcripts PAX/FKHR were identified in 13 of 15 patients with alveolar RMS. Furthermore, the fusion transcript PAX7/FKHR was identified in 2 of 15 patients with RMS classified as embryonal by histology. Bone marrow samples (12) and peripheral blood progenitor cell specimens (13) in ten patients were examined by RT-PCR. We were able to identify 7 patients with bone marrow involvement and/or with contamination of peripheral blood progenitor cells by the tumor cells. We demonstrate that employing molecular diagnostics has an impact on staging, therapy monitoring and recognition of malignant cells at the tumor resection margins.

Orbital-conjunctival glomangiomas involving two ocular rectus muscles.

PURPOSE: To report two glomangiomas in one orbit, each isolated to a rectus muscle. DESIGN: Clinicopathologic correlation. METHODS: A 12-year-old boy developed two separate vascular tumors, near the insertions of the medial rectus and superior rectus muscles, respectively. A biopsy of one tumor was studied by light microscopy and immunohistochemistry. RESULTS: Histopathology revealed blood vessels surrounded by cuboidal cells characteristic of glomangioma. The cells showed immunoreactivity for smooth muscle actin and vimentin, supporting the diagnosis. CONCLUSIONS: Glomangioma can involve the rectus muscles in the conjunctiva and orbit, and should be considered in differential diagnosis of vascular tumors in the ocular region.

Pseudolipoblastic perineurioma: an unusual morphological variant of perineurioma that may simulate liposarcoma.

Perineuriomas are rare peripheral nerve sheath tumors arising from or differentiating along the lines of normal perineurial cells. They can be divided into intraneural and soft tissue types, with the latter category including a significant number of morphological variants. Herein, we further expand their morphological spectrum to include "pseudolipoblastic" perineuriomas. These lesions occurred in the tongue of a 30-year-old man and in the triceps of a 67-year-old woman and were characterized by bland, epithelioid cells with striking intracytoplasmic vacuolization. The architecture varied, with some areas showing a striking "net-like" or "microreticular" pattern and smaller areas having a more typical spindled and whorled appearance. Clinical follow-up (5months and 52months, respectively) showed no evidence of local recurrence or metastasis. Multiple perineurial markers, including epithelial membrane antigen, claudin-1, GLUT-1, and collagen IV, were diffusely positive. Both cases were submitted in consultation out of concern that they represented high-grade liposarcomas. To the best of our knowledge, this unusual morphological variant of perineurioma has not been reported. These tumors appear to be entirely benign and should be cured with simple excision. Pseudolipoblastic perineuriomas should be distinguished from round cell and epithelioid pleomorphic liposarcomas, as well as from other tumors that may show prominent intracytoplasmic vacuolization.

Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features.

Two cases of histiocytic sarcoma with BCL2 translocations and occult or subsequent follicular lymphoma.

Histiocytic sarcoma is rare and difficult to distinguish from histologic mimics such as myeloid sarcoma due to its relatively nonspecific immunoprofile. A subset of histiocytic sarcomas are clonally related to synchronous or metachronous follicular lymphomas. Interestingly, the histiocytic tumor component has been shown to harbor BCL2 gene translocations that are identical to those found in the lymphoma. We present one case of histiocytic sarcoma and initially occult follicular lymphoma in which detection of a BCL2 gene translocation helped support the diagnosis. We also provide follow-up regarding a previously published case of histiocytic sarcoma with IGH/BCL2 fusion gene in which the patient subsequently developed follicular lymphoma and, later, diffuse large B-cell lymphoma. Our findings suggest that BCL2 gene translocations are a recurrent feature of a distinct subset of histiocytic sarcomas that are associated with follicular lymphoma; the follicular lymphoma component may be clinically occult at the time of diagnosis. Testing for an IGH/BCL2 translocation should be considered in the diagnostic workup of difficult-to-characterize neoplasms with histiocytic/monocytic morphology and immunoprofile.

Dendritic fibromyxolipoma in the latissimus dorsi: a case report and review of the literature.

Dendritic fibromyxolipoma is an uncommon benign soft tissue tumor. Here, we report a case in a 53-year-old man presenting a painless mass located deep in the latissimus dorsi of the right back. Microscopically, the tumor was mainly consisted of small spindle and stellate cells, abundant myxoid stroma, collagen bundles and mature adipose tissue. Immunohistochemical study showed the spindle and stellate cells were positive for CD34, Bcl-2 and Vimentim, but not for Keratin, EMA, SMA and Desmin. To date, one year after operation, the patient is well without evidence of recurrence or metastasis. The implication of this report is to provide insights into further understanding of this rare tumor with review of the literature.

Gastrointestinal stromal tumor solitary distant recurrence in the left brachialis muscle.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are most commonly found in the stomach. Although GISTs can spread to the liver and peritoneum, metastasis to the skeletal muscle is very rare and only four cases have previously been reported. These cases involved concurrent skeletal metastases of primary GISTs or liver metastases. Here, we report the first case of a distant recurrence in the brachialis muscle after complete remission of an extra-luminal gastric GIST following a wedge resection of the stomach, omental excision, and adjuvant imatinib therapy for one year. Ten months after therapy completion, the patient presented with swelling and tenderness in the left arm. Magnetic resonance imaging revealed a large mass in the brachialis muscle, which showed positivity for c-kit and CD34 upon pathologic examination. This is the first reported case of a solitary distant recurrence of a GIST in the muscle after complete remission had been achieved.

A distinctive myointimal proliferation ('myointimoma') involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases.

This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.

Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study.

We reviewed six cases of rhabdomyosarcoma as a rare second primary malignancy in children with bilateral retinoblastoma after irradiation treatment. The patients comprised four females and two males (age range 1 year 4 months-7 years 11 months). Second tumors arose in the temporal muscle inside or close to the previously irradiated fields. All the children were alive and well 24-72 months after diagnosis. Microscopic examination showed proliferation of closely packed, small round cells with scanty cytoplasm, coarse nuclear chromatin, and increased mitotic activity without a myxoid background nor obvious alveolar architecture. The most characteristic feature was the presence of rosette-like structures in four tumors. Immunoreactivity for many skeletal muscle markers was evident, including desmin (six of six), muscle-specific actin (HHF35) (six of six), sarcomeric actin (six of six), myogenin (six of six), vimentin (six of six), and myoglobin (three of six). On reverse transcriptase-polymerase chain reaction examination, three second tumors lacked specific chimeric transcripts for alveolar rhabdomyosarcoma and Ewing's sarcoma. Unexpectedly, variable reactivity for neurofilament (150 kd) was identified in six of six second tumors as well as 15 of 20 sporadic primary rhabdomyosarcomas (75%) examined as controls, the result being confirmed by Western blot analysis. In addition, staining for retinoblastoma-susceptibility gene protein was negative in all second tumors, in contrast to positivity in 14 of 17 sporadic primary tumors (82%). This finding suggests that retinoblastoma-susceptibility gene abnormalities could be associated with the development of second primary rhabdomyosarcoma. We consider that knowledge of the occurrence of rhabdomyosarcoma and appropriate immunohistochemical study are helpful for avoiding a misdiagnosis of recurrent retinoblastoma or Ewing's sarcoma when encountering patients with a history of bilateral retinoblastoma who developed second small round cell neoplasms.