A Collision Tumor Involving a Primary Leiomyosarcoma of the Lower Extremity and a Metastatic Medullary Thyroid Carcinoma: A Case Report.

CASE: A 49-year-old man presented with a rapidly growing thigh mass. Histologic analyses demonstrated separate regions that were consistent with a collision tumor composed of a primary leiomyosarcoma and a metastatic medullary thyroid carcinoma. After responding to chemotherapy, the patient underwent resection of the tumor and a total thyroidectomy; he was disease-free 9 years after the diagnosis. CONCLUSION: A wide diagnostic differential and thorough histologic analysis are necessary in patients presenting with neoplasms of the extremities. A leiomyosarcoma may be a hospitable location for metastatic disease, and the presence of a collision tumor should be considered when pathology findings are equivocal.

Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required.

Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid.

BACKGROUND: Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon. The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. PURPOSE: Zoledronic acid-associated baboon syndrome is described in a woman with recurrent metastatic breast cancer. METHODS: PubMed was used to search the following terms, separately and in combination: baboon syndrome, breast cancer, symmetrical drug-related intertriginous and flexural exanthema, and zoledronic acid. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. RESULTS: Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. However, baboon syndrome has not previously been observed in patients receiving zoledronic acid. The reported woman developed baboon syndrome after her initial exposure to zoledronic acid. CONCLUSIONS: Non-contact allergenic drug-induced baboon syndrome has most commonly been associated with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated baboon syndrome has not previously been observed in cancer patients. Baboon syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can occur in oncology patients receiving zoledronic acid and zoledronic acid should be added to the list of medications associated with the potential to cause non-contact allergenic drug-induced baboon syndrome.

Paclitaxel-ifosfamide-carboplatin combination chemotherapy regimen in advanced uterine and adnexal malignant mixed Mullerian tumours.

BACKGROUND: Malignant mixed Mullerian tumours (MMMTs) of the uterus and adnexa represent aggressive gynaecologic malignancies with a high rate of loco-regional and distant failure. For that reason, we evaluated the paclitaxel-ifosfamide-carboplatin (TICb) combination in patients with advanced MMMTs. METHODS: Female patients with advanced MMMTs, WHO-PS 0-2, no prior chemotherapy for systemic disease, unimpaired haemopoietic and organ function were eligible. Chemotherapy was administered at the following doses; paclitaxel: 175 mg m(-2) on day 1, ifosfamide: 2.0 g m(-2) day(-1)--days 1 and 2, and carboplatin at a target area under the curve 5 on day 2, with prophylactic G-CSF from day 3. RESULTS: Forty patients of a median age 61 (45-72) years, performance status 0-2 with advanced MMMTs of the uterus (n=34), tubes (n=2) or ovary (n=4) have entered and all were evaluable for response and toxicity. Responses were as follows: 27 out of 40 (67.5%) evaluable patients responded, with 11 complete responses and 16 partial responses, while 10 had stable disease, and 3 developed progressive disease. The median response duration was 9 months (range, 4-40 months), median progression-free survival 13 months (range, 3-42 months), while median overall survival 18 months (range, 4-48 months). Grade 3/4 neutropenia was recorded in 22 out of 40 (55%)--with 13 developing grade 4 (≤7 days) and 7 out of 40 (17.5%) of patients at least one episode of febrile neutropenia. CONCLUSION: In this study, it appears that the TICb combination, yielded important activity with manageable toxicity in females with advanced MMMTs warranting further randomised comparison with current standard regimens.

Placental-site trophoblastic tumors: a case of resistant pulmonary metastasis.

Background A 52-year-old woman whose last known pregnancy was 12 years before presentation was diagnosed with mixed trophoblastic tumor that included placental-site trophoblastic tumor, epithelioid trophoblastic tumor, and focal choriocarcinoma. There was no clear evidence of metastatic disease on initial evaluation. Investigations Histopathology, laboratory tests, immunohistochemistry, chest X-ray, CT scan of the chest, abdomen, and pelvis, fine-needle aspiration biopsy, PET-CT scan.Diagnosis Metastatic chemoresistant placental-site trophoblastic tumor positive for EGFR, VEGF receptor, and platelet-derived growth factor receptor. Management Abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic radiation, etoposide, methotrexate, actinomycin D/cyclophosphamide and vincristine chemotherapy, left thoracotomy with wedge resection, taxol, etoposide, cisplatin therapy, right thoracotomy with wedge resection.

Recurrent prostatic stromal sarcoma with massive high-grade prostatic intraepithelial neoplasia.

A unique case of prostatic stromal sarcoma (PSS) that recurred in the pelvic cavity with massive high-grade prostatic intraepithelial neoplasia is described. A 52-year-old man who presented with urinary retention underwent a radical cystoprostatectomy. Tumour tissues of the prostate showed an admixture of hyperplastic glands and markedly cellular stroma of spindle cells arranged in a fascicular pattern, and the tumour was diagnosed as PSS. 66 months after the operation, CT scans revealed three recurrent tumours around the bilateral obturator and left fore iliopsoas. The recurrent tumours were biphasic neoplasms, as before, but the epithelial component had grown prominent and manifested overt atypia in a manner resembling high-grade prostatic intraepithelial neoplasia. Our findings suggest that not only the stromal component but also and the epithelial components of PSS may have malignant potential.

Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract.

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.

Sialoblastoma: a clinicopathologic and immunohistochemical study of 7 cases.

Sialoblastoma is a rare congenital or perinatal salivary tumor that varies in histologic features and biologic potential. Seven cases from the files of the Armed Forces Institute of Pathology are presented. These tumors occurred in 4 males and 3 females with ages ranging from prenatal to 6 months at the time of discovery. Five lesions originated from the parotid gland; 2 lesions were from the submandibular gland. All lesions presented as nodular to multinodular swellings and ranged in size from 2.0 to 7.0 cm. The principal sign or symptom was rapid growth. Two histologic patterns with differing behavior predominated: (1) a favorable pattern had semiencapsulation of cytologically benign basaloid tumor cells with intervening stroma; and (2) an unfavorable histology of anaplastic basaloid tumor cells, minimal stroma, and broad pushing to infiltrative periphery. Four and three tumors had favorable and unfavorable growth patterns, respectively. One unfavorable lesion had vascular invasion, and another demonstrated perineural invasion. All 3 tumors with unfavorable histology recurred. Tumor cells in 3 cases were immunohistochemically reactive for keratin, S-100, smooth muscle actin, and calponin to varying degrees. All 3 tumors were reactive for p63. alpha-Fetoprotein was expressed in 2 unfavorable tumors. Ki67 was expressed at 3% in a favorable tumor and 40% and 80% in the 2 unfavorable lesions. Treatment involved surgical excision. One patient received adjuvant chemotherapy. Two sialoblastomas resulted in recurrences within a year and another developed a recurrence after 4 years. One sialoblastoma developed lung metastasis within 1 month of the original biopsy. Although a clinical correlation is suggested by a favorable/unfavorable histologic grading system the biologic behavior is nonetheless considered unpredictable.

Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma involving the maxillary gingiva.

Gingival metastases are infrequent and invariably associated with a widespread disease and a poor prognosis. Because of their unremarkable clinical appearance, they can be difficult to distinguish from more common gingival hyperplastic or reactive lesions, such as pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying granuloma. We are reporting here an unusual case of a 36-year-old man with a mixed testicular germ cell tumor presenting as a metastatic pure choriocarcinoma involving the maxillary gingiva, extending from the first left premolar to the left second maxillary molar, mimicking a 'benign looking' gingival mass. Gingival metastases may be the first manifestation of a widespread metastatic disease and therefore particular attention must be paid to gingival lesions associated with atypical clinical symptoms and/or signs.

Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)--report of six cases.

BACKGROUND: Malignant mixed mesodermal tumours (MMMT) of the female genital tract are rare and heterogeneous malignancies that impart grim prognosis. These tumours are characterized by an admixture of malignant epithelial and stromal elements comprising carcinomatous and sarcomatous neoplastic cells. Thus far, almost 350 cases of MMMT have been recorded in the international medical literature. Due to its rarity, there is no agreement on the best treatment strategy in women with metastasized MMMT. METHODS: Six women (mean age 59 years) with metastasized MMMT defined to the peritoneal cavity have been treated by cytoreductive surgery plus hyperthermic peritoneal perfusion plus postoperative adjuvant chemotherapy. All patients have been pre-treated by surgery for primary tumour and one by systemic chemotherapy. As cytostatics for hyperthermic peritoneal perfusion, we have used Mitomycin in a dosage of 18 mg/m2 plus Melphalan in a dosage of 25 mg/m2. As adjuvant treatment CDDP 40 mg/m2/dl, Mitomycin 7 mg/md2/dl and Ifosfamid 100 mg/kg 24 h/dl was applicated via intraaortic catheter three times with a treatment free interval of 3 weeks. RESULTS: A complete cytoreduction without remnant tumour formations in the peritoneal cavity could be carried out in all six patients. The postoperative course was uneventful in all cases except for one where a spontaneous small bowel perforation and prolonged gall secretion had to be treated by re-operation. One patient died 4 months later by pneumonia without evidence of disease. Four patients are without evidence of disease after 2, 4, 14 and 19 months, whereas one patient developed liver metastases after 9 months still treated by systemic chemotherapy. CONCLUSION: Complete cytoreduction plus hyperthermic peritoneal perfusion plus adjuvant chemotherapy seems to be an effective treatment for recurrent or metastasized MMMT. Further studies have to define the value of this new treatment strategy for this rare tumour entity.

Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation.

We report the clinicopathologic features of 24 uterine primary and metastatic endometrial stromal sarcomas with fibromyxoid features (ESS-F) and smooth muscle differentiation (ESS-SM) (endometrial stromal sarcoma variants). Two groups of tumors were retrieved from the surgical pathology files at Memorial Sloan-Kettering Cancer Center: 1) gynecologic mesenchymal neoplasms with striking smooth muscle or fibroblastic differentiation that did not meet the clinical or histologic criteria for leiomyosarcoma or other established neoplasms containing smooth muscle; and 2) metastatic lesions showing ovoid and spindle cell morphology, involving lung, originally diagnosed as low-grade leiomyosarcoma, low-grade smooth muscle neoplasm, intravenous leiomyomatosis, fibrous hamartoma, and benign metastasizing leiomyoma. We identified 12 patients with 30 tumors; 24 were available for review. The mean age was 51 years (range 21-74 years). Follow-up >1 year was available for eight patients, with a mean time of 8.5 years. Each patient had a uterine primary and 10 experienced metastases. Mean time to recurrence was 6.8 years. Sites of metastasis included lung, retroperitoneum, right atrium/inferior vena cava, colon, and ovaries. No patient died of disease, but in many cases the follow-up period ended with the discovery of a metastasis. Four patients were originally diagnosed with endometrial stromal sarcoma, but other presenting diagnoses included benign metastasizing leiomyoma, fibroleiomyomatous tumor of lung, smooth muscle tumor of uncertain or low malignant potential, and intravascular leiomyomatosis. On review each patient had at least one tumor (primary and/or metastasis) that was determined to be an endometrial stromal sarcoma variant. Review diagnoses were as follows: endometrial stromal sarcoma (nonvariant), ESS-F, and ESS-SM. Eight of 10 primary tumors with available slides were endometrial stomal sarcoma variants (six ESS-F and two ESS-SM). When these variant features were present, they comprised between 50% and 100% of the neoplasm. The variant histology tumors exhibited prominent spiral arterioles, perivascular edema, and stromal cell condensation around blood vessels. All metastases but one were variant tumors; eight were ESS-F and five were ESS-SM. Four metastases did not resemble the uterine primary. Desmin marked smooth muscle mostly but not specifically. h-Caldesmon marked smooth muscle exclusively. Endometrial stromal cells as well as some fibroblasts and smooth muscle cells expressed CD10. We conclude that the presence of even focal endometrial stromal differentiation in an invasive uterine mesenchymal lesion with a predominant low-grade smooth muscle, fibroblastic, and/or myxoid phenotype should permit classification as low-grade sarcoma-they should be considered endometrial stromal sarcomas.

[Metastatic renal tumor of malignant salignant salivary-gland-like tumor of the lung: A case report].

A 17-year-old woman was admitted to our hospital for the investigation of asymptomatic gross hematuria. Twenty nine months ago, she had received the right lower lobectomy because of the malignant salivary gland type mixed tumor of the bronchus. The intravenous pyelography and the right retrograde pyelography showed the irregular wall of the right renal pelvis. The computerized tomography showed a hypodense tumor which occupied the lower half of the right kidney. Cystoscopy showed bleeding from the right ureteral orifice. Chest X-ray revealed multiple lung metastases at the first examination, but right nephrectomy was performed because gross hematuria continued. The tumor thrombus, which spreaded into vena cava, was removed. The pathological diagnosis was the metastatic renal tumor of malignant salivary gland type mixed tumor. The patient died 102 days postoperatively.

Nonsyntenic amplification of MYC with CDK4 and MDM2 in a malignant mixed tumor of salivary gland.

Karyotypic analysis of a metastatic malignant mixed tumor of the salivary gland revealed the presence of double minute chromosomes (dmin), indicative of gene amplification. Comparative genomic hybridization analysis of DNA extracted from the primary and a renal metastasis indicated overt amplification of DNA sequences derived from 8q23-24 and 12q13-15 regions. Subsequent Southern blot analysis of tumor DNA from the metastasis with the use of probes previously mapped to those regions indicated amplification of MYC at 8q23-24 and CDK4 and MDM2 at 12q13-15. Fluorescence in situ hybridization of differentially labeled MYC and MDM2 genes hybridized to tumor metaphase chromosomes revealed an independent nonsyntenic amplification of MYC and MDM2 on dmin in this tumor.

Malignant mixed tumor of the skin (malignant chondroid syringoma).

Two cases of malignant mixed tumor of skin were studied, one of which demonstrated regional metastasis. The immunohistochemical features of these 2 neoplasms and of the 2 malignant mixed tumors previously described in Western Australia indicate that these neoplasms show eccrine differentiation and suggest their origin from both the secretory and ductal segments of the gland. The histological criteria of malignancy are discussed, with particular reference to those features which indicate malignant potential in neoplasms which otherwise lack overt morphological criteria of malignancy.

Indication for neck dissection in carcinoma of the parotid gland. Our experience on 39 cases.

In cases of parotid carcinoma, the percentage of cervical metastases, at the time of first observation is 18%. Consequently, the evaluation of the grade of lymphatic involvement is very important in order to plan a correct therapy. The authors underline the important role that neck dissection has in the treatment of these tumours. There are different points of view on neck dissection in cases of malignant parotid tumours. While there is no doubt with regard to indications on neck dissection in N + patients, the problem does exist for N-patients. The Authors have analyzed 39 patients with malignant parotid tumours observed at the Department of Maxillo-Facial Surgery of the "Federico II" University of Naples.