Metastasizing mixed tumor of the parotid: initial presentation as a solitary kidney tumor and ultimate carcinomatous transformation at the primary site

Benign mixed tumors of the salivary glands are generally regarded as indolent and harmless neoplasms. A subset of benign mixed tumors, however, can undergo carcinomatous transformation (that is, carcinoma ex-mixed tumor). Even more rarely, a mixed tumor that is seemingly benign at the microscopic level will metastasize like a true carcinoma (that is, metastasizing mixed tumor [MZMT]). Despite the benign appearance of the metastatic implants, there is usually little doubt regarding their true nature and origin. Patients invariably have had a mixed tumor removed from the parotid or some other salivary gland, and metastatic spread is usually preceded by multiple episodes of local tumor recurrence. We report a case of MZMT that presented as a solitary kidney mass. In the absence of a previous or concurrent salivary gland tumor, its metastatic nature was not appreciated and it was regarded as an unusual but benign kidney adenoma. One year after removal of the kidney mass, the patient presented with signs and symptoms of an aggressive parotid tumor. Pathologic examination of the tumor in the parotid demonstrated a high-grade carcinoma arising from a mixed tumor. This case underscores the importance of considering MZMT when a seemingly benign mixed tumor is encountered at a nonsalivary site, even in patients without a supportive history. Failure to do so may cause an unnecessary delay in primary tumor diagnosis and management, allow the primary tumor to progress toward a more malignant phenotype, and deny the patient a high expectation for a complete cure.     

Carcinoma ex Pleomorphic Adenoma of the Nasal Cavity

Background  

Carcinoma ex pleomorphic adenoma (CXPA) is a malignant epithelial neoplasm arising in a benign mixed tumor (i.e., pleomorphic adenoma or PA); it accounts for approximately 3–4% of all salivary gland neoplasms. CXPA is exceedingly rare in the nasal cavity, with only three cases previously documented.     

Malignant mixed tumor of the lacrimal gland.

This paper reports a case of carcinoma arising in a benign mixed tumor of lacrimal gland following multiple recurrences. The patient had eight recurrences of the benign lesion and after 32 years developed an adenocarcinoma associated with recurrent nodules of still recognizable benign mixed tumor. The literature on malignant mixed tumors of the lacrimal gland is reviewed noting the confusion in diagnostic terminology in early reports. Our patient illustrates the resemblance between malignant mixed tumor (carcinoma arising in pleomorphic adenoma) of lacrimal and salivary gland both clinically and pathologically.     

Myoepithelial Neoplasms of Soft Tissue: An Updated Review of the Clinicopathologic,Immunophenotypic, and Genetic Features

Myoepithelial tumors in skin and soft tissue are uncommon but have been increasingly characterized over the past decade. Men and women are equally affected across all age groups and lesions arise most frequently on the extremities and limb girdles. Approximately 20 % of cases occur in pediatric patients, in whom they are frequently malignant. Similar to their salivary gland counterparts, myoepithelial tumors of soft tissue demonstrate heterogeneous morphologic and immunophenotypic features. Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma; in soft tissue, tumors having at least moderate cytologic atypia are classified as malignant. Mixed tumor and myoepithelioma show a benign clinical course, with recurrence in up to 20 % (typically secondary to incomplete excision), and do not metastasize. In contrast, myoepithelial carcinoma shows more aggressive behavior with recurrence and metastasis in up to 40–50 % of cases. The majority of myoepithelial neoplasms typically coexpress epithelial antigens (cytokeratin and/or EMA) and S-100 protein; GFAP and p63 are frequently positive and a subset of malignant neoplasms lose INI1 expression. Up to 45 % of myoepitheliomas and myoepithelial carcinomas harbor EWSR1 gene rearrangements, unlike mixed tumor/chondroid syringoma which is characterized by PLAG1 gene rearrangement. While mixed tumor/chondroid syringoma are likely related to primary salivary myoepithelial tumors, soft tissue myoepithelioma and myoepithelial carcinoma appear to be pathologically distinct neoplasms.     

Mixed odontogenic tumors: an analysis of 23 new cases

The ameloblastic fibroma, ameloblastic fibrodentinoma, and ameloblastic fibro-odontoma are mixed odontogenic tumors that are considered to arise from both epithelial and mesenchymal elements of the tooth germ. This article presents the clinical and histopathologic characteristics of 23 new cases. The patients' ages ranged from 3 to 19 years (median 9). Most tumors were asymptomatic and were associated with an unerupted tooth or teeth. All patients were treated with simple enucleation of the tumor. We found that histologically these lesions comprise a spectrum. Some were probably benign odontogenic tumors (neoplasms) and others were odontomas undergoing maturation (hamartomas); however, in any given case we were, on histologic grounds, unable to differentiate the two. The majority, if not all, of our cases were nonaggressive with little or no tendency to recur, whereas some reported cases have exhibited local aggressiveness and recurrence, suggestive of neoplasia. In our opinion, it is clinically important to distinguish the mixed odontogenic tumors from ameloblastoma since the mixed tumors, found mostly in children, are relatively benign when compared to ameloblastoma, which is found in all age groups (usually adults). The usually innocuous behavior of these lesions does not justify aggressive treatment initially, and simple enucleation should be appropriate in most cases.     

Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters

Myoepitheliomas and mixed tumors were only recently recognized to occur primarily in soft tissue, and only small case numbers have been described. To characterize these tumors further and to evaluate prognostic parameters, 101 myoepithelial tumors of soft tissue were retrieved from the authors' consult files. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring physicians. Fifty-three patients were male and 48 female (mean age 38 years; range 3-83 years). Tumor size ranged from 0.7 to 20 cm (mean 4.7 cm). Most tumors arose in the extremities and limb girdles: 41 in the lower limbs, 35 in the upper limbs, 15 in the head and neck, and 10 in the trunk. Fifty-four tumors were situated in subcutis and 37 in deep soft tissue (depth unstated in 10). Most cases were grossly well circumscribed; 43 showed microscopically infiltrative margins. Histologically, most tumors were lobulated, composed of cords or nests of epithelioid, ovoid, or spindled cells with a variably reticular architecture and a chondromyxoid or collagenous/hyalinized stroma. Eight cases showed a predominantly solid proliferation of spindled or plasmacytoid cells; 17 demonstrated ductular differentiation (mixed tumors). Cartilage was present in 6 cases, 6 contained bone, and 4 others contained both. Mitoses ranged from 0 to 68 per 10 high power fields (mean 4.7 per 10 high power fields). Tumors with benign cytomorphology or mild cytologic atypia (low-grade) were classified as myoepithelioma or mixed tumor, whereas tumors with moderate to severe atypia (high-grade) were classified as myoepithelial carcinoma (epithelioid or spindled cells with vesicular or coarse chromatin, prominent, often large nucleoli, or nuclear pleomorphism) or malignant mixed tumor (cytologically malignant cartilage or bone). Sixty-one cases were myoepitheliomas or mixed tumors, and 40 were myoepithelial carcinomas or malignant mixed tumors. By immunohistochemistry, all cases with available material were reactive for epithelial markers (keratins and/or epithelial membrane antigen): 90 of 97 (93%) expressed keratins (most often AE1/AE3 or PAN-K), 84 of 97 (87%) S-100 protein, 44 of 51 (86%) calponin, 52 of 83 (63%) epithelial membrane antigen, 40 of 87 (46%) glial fibrillary acidic protein, 27 of 75 (36%) smooth muscle actin, 15 of 66 (23%) p63, and 7 of 51 (14%) desmin. Follow-up was available for 64 patients. Among 33 cases with benign or low-grade cytology (mean follow-up 36 months; range 4-168 months), 6 recurred locally (18%) and none metastasized. No clinical or histologic features correlated with recurrence. Among 31 cytologically malignant cases (mean follow-up 50 months; range 4-252 months), 13 recurred locally (42%) and 10 metastasized (32%); so far, 4 patients have died of metastatic tumor. This study expands the spectrum of myoepithelial tumors of soft tissue to include myoepithelial carcinomas and malignant mixed tumors, which pursue an aggressive clinical course. Although the majority of morphologically benign or low-grade myoepithelial neoplasms of soft tissue behave in a benign fashion, there is an approximate 20% risk for local recurrence.     

Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis.

Among salivary gland neoplasms are a group of rare tumors that are histologically identical to benign mixed tumors that inexplicably metastasize; they have been called metastasizing mixed tumor (MZMT) of salivary glands. We report the clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At the time of discovery of metastatic disease, the patients, six women and five men, ranged in age from 20 to 83 years. Primary sites of involvement included the parotid gland (eight cases), submandibular gland (two cases), and the nasal septum (one case). With one exception, all the patients had at least a single recurrences of their primary mixed tumor, but two or more recurrences were the norm before development of metastatic foci. The metastases were discovered from six to 52 years following the occurrence of the primary tumor. Metastatic deposits were identified in bone, lung, regional lymph nodes, skin, kidney, retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The metastases either occurred simultaneously with an episode of recurrent mixed tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of the primary, recurrent, and metastatic neoplasms was surgical excision. Follow-up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed seven patients to be alive without disease (64%) and two dead of causes unrelated to metastatic disease (18%). Two patients (18%) died as a direct result of metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow cytometric analysis revealed a diploid DNA cell population in the primary and/or metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two of the cases. DNA ploidy levels and cell proliferation rates were compared with those of conventional benign mixed tumors and also with malignant mixed tumors. Retrospective analysis of histologic parameters (mitotic rate, cellular pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow cytometric analysis failed to identify criteria to predict the development of metastasis in these neoplasms.     

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands

Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.     

Synchronous benign and malignant salivary gland tumors in ipsilateral glands: a report of two cases and a review of literature

BACKGROUND: Ipsilateral salivary gland tumors of different histologic types are rare and make up less than 0.3% of all salivary gland neoplasms. Only nine cases of synchronous benign and malignant ipsilateral parotid gland tumors have been described in the literature. METHODS: Two additional cases of synchronous benign and malignant neoplasms in the parotid gland are reported and discussed with a review of literature. RESULTS: Our first case describes a pleomorphic adenoma and a salivary duct carcinoma, an entity not previously reported in the literature. The second case documents the most common benign and malignant ipsilateral parotid gland neoplasm reported in this case series, a Warthin's tumor and a mucoepidermoid carcinoma. CONCLUSIONS: Synchronous salivary gland tumors exhibiting both benign and malignant components are uncommonly observed, with only nine cases published to date. We describe two additional cases of a synchronous benign and malignant ipsilateral parotid gland tumor.     

乳腺错构瘤8例分析

目的：总结乳腺错构瘤病理特点并分析其临床,组织学及免疫组织化学（免疫组化）特征。方法：组织标本经10％福尔马林固定,常规石蜡切片,HE染色,用SP法进行免疫组织化学标记。结果：8例错构瘤组织学镜下境界清楚,由数量不等的纤维,脂肪,乳腺小叶及导管成分组成,上皮成分无非典型性,出现不同程度雌激素受体（ER）阳性。结论：乳腺错构瘤为良性病变,组织学上与其它乳腺肿瘤不同,与雌激素水平有关,确诊需临床,X线及病理相结合。     

Rare kidney tumors

During the period from 1976 to 1986, a total of 518 kidney tumor patients were treated in the Department of Urology at the University of Freiburg, West Germany. In 34 cases (6.6%) the examination revealed a tumor that was neither a renal cell carcinoma nor a renal pelvic urothelial carcinoma (i.e., a rare renal tumor). Through diagnostic imaging procedures the presence of a tumor was correctly diagnosed in 97% of these 34 cases. Conservative treatment methods were used with 5 patients (4 with renal angiomyolipoma and 1 with hemangioma) whose conditions were clearly diagnosed. In these patients operative therapy was not indicated. The precise histological diagnosis found in 29 patients subjected to surgery was the same as the preoperative diagnosis in only 8 cases (27.6%). Histologically, 20 benign (4 epithelial, 16 mesenchymal) and 9 malignant (3 epithelial, 3 mesenchymal, 3 mixed) tumors were found. The operative methods for rare kidney tumors are the same as those used for the more common kidney tumors. Only in the presence of tumors that are clearly benign, such as angioma or angiomyolipoma, is a wait and see policy with frequent examinations recommended.     

Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant adenomyoepithelioma) with associated breast malignancies: A case series emphasizing histologic,radiologic, and clinical correlation

The 2012 World Health Organization (WHO) classification of breast tumors distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic proliferation of phenotypically variable myoepithelial cells around small epithelial lined spaces. Many AMEs have demonstrated benign behavior and are often cured with excision with negative margins, but some have exhibited malignant transformation of the myoepithelial cells, ductal epithelial cells, or both. When one of the components is histologically malignant, it is termed AME with carcinoma. Due to the rarity, the literature correlating imaging, histology, and clinical outcome is limited. A retrospective review was undertaken. A review of an institutional pathology database identified 14 cases with AME or malignant AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads 4. Histologic features of AME did not correlate with prior or concurrent breast malignancies or any radiographic features. Clinical follow up could be obtained for all but one case (mean follow up time = 75 months). 5 cases had no known treatment post-biopsy and 5 patients received mastectomy. No recurrences were noted. 3/13 cases of benign AME had associated breast malignancies including invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant AME had a synchronous separate malignant phyllodes tumor. Given the unclear and unpredictable propensity for malignant transformation, conservative excision with negative margins currently seems appropriate.     

Sclerosing polycystic adenosis of the salivary gland: a report of 16 cases

Sclerosing polycystic adenosis is a recently described, extremely rare, reactive, sclerosing, inflammatory process somewhat similar to fibrocystic changes and adenosis tumor of the breast. To date, there have been 22 cases described in the literature. Because of the infrequency of this lesion, we describe our combined experience with 16 cases, 1 of which has been previously reported. Thirteen tumors arose in the parotid gland, two involved the submandibular gland, and one arose in the buccal mucosa. There were 9 men and 7 women. Patients ranged in age from 9 to 75 years. Fourteen patients presented with a primary mass. Two were incidental findings in patients with a mixed tumor and an oncocytoma. Tumors ranged in size from 0.3 to 6 cm in greatest dimension. They are typically well circumscribed and are composed of densely sclerotic lobules with prominent cystic change. Hyperplasia of ductal and acinar elements and areas of apocrine-like metaplasia are frequent. Foci with mild ductal epithelial atypia were frequent with >50% of cases demonstrating at least focal areas of duct epithelial hyperplasia with atypia. Follow-up ranged from 1.5 to 40 years. One tumor recurred twice; no patient has developed metastases or died of disease.     

Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity

Mammary analog secretory carcinoma (MASC) is a recently described tumor predominantly arising in the parotid gland. These tumors represent locally invasive malignancies with microcystic architecture, low-grade nuclei, and granular pink vacuolated cytoplasm. They display strong vimentin and S100 positivity and harbor an identical t(12;15)(p13;q25) to their breast counterpart, leading to a ETV6-NTRK3 fusion oncogene. These features help exclude the most important differential diagnostic considerations, namely, acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, not otherwise specified. Here we present a series of 7 recent examples of MASC, which showed features not previously described. These 7 cases were observed in patients ranging in age from 14 to 77 years (mean, 40 y), occurred almost exclusively in male patients (6:1), and showed >50% (4 of 7 cases) involvement of the oral cavity, with only 2 arising in the parotid. The remaining case is the first reported in the submandibular gland. The tumors showed a variety of patterns including single macrocysts, combined macrocystic and microcystic spaces, and solid architecture. They showed prominent hobnailing in the cystic areas. Secretions within the cysts and tubular areas tended to be positive for periodic acid schiff, periodic acid schiff diastage and mucicarmine, the latter also showing occasional intracytoplasmic mucin droplets, a feature not previously recognized. One case showed prominent mucinous differentiation, which, coupled with high-molecular-weight keratins (HMWK) positivity, mimicked mucoepidermoid carcinoma (MEC). The tumors were generally positive for HMWK (6 of 7), S100 (5 of 7), vimentin, CK19, and other epithelial markers. The finding of duct involvement, proven with an incomplete p63-positive basal layer surrounding a minority of tumor cell nests and cysts, raised the possibility of a ductal epithelial origin for MASC. Alternatively, this could represent secondary ductal involvement by tumor. All cases showed rearrangement of the ETV6 gene by fluorescence in situ hybridization, confirming the diagnosis of MASC. These findings reinforce MASC as a unique low-grade salivary gland tumor entity with morphologic overlap with AciCC, MEC, and cystadenocarcinoma.     

Angiosarcoma arising in hemangioma/vascular malformation: report of four cases and review of the literature

Malignant change in a benign vascular tumor is exceedingly rare, and there have been only five previously reported convincing cases. Four new cases of angiosarcoma (AS) arising in a hemangioma/vascular malformation (HVM) are described. All patients were in the 6th or 7th decade of life (two female, two male). Development of an enlarging deep-seated mass was the main presenting symptom. MRI disclosed the presence of two separate soft tissue masses in both thighs in one patient. No patient had a history of prior radiotherapy at the same site. Preoperative duration, known in three cases, ranged from 1 to 24 months (median 12 months). Three tumors were located in the lower extremities (thigh and buttock), one in the retroperitoneum, and one in the parotid region. Three patients were treated by marginal excision; in one case only a biopsy was performed. Radiotherapy/chemotherapy was given in all cases. Two patients were disease free 2 and 14 months after surgery and two developed metastases. Grossly, the tumors were described as frankly hemorrhagic masses or as firm, whitish areas with hemorrhagic nodules and were centered in skeletal muscle in three cases. Size ranged between 2.2 cm and 8 cm (median 4.3 cm). Histologically, all the tumors had two distinct components. In three cases the benign and the malignant components were variably intermixed, whereas in one case the HVM was mainly located at the edge of the malignant tumor. The benign component showed features of an arteriovenous hemangioma (three cases) or intramuscular capillary hemangioma. AS showed epithelioid morphology in three cases and a well-differentiated dissecting pattern in one case. An imperceptible transition between the two components was noted in two cases. The two anatomically separate masses excised from one patient appeared almost identical. All cases were positive for at least two endothelial markers (CD31, CD34, VWF) and negative for the epithelial markers (EMA, AE1/AE3, Pan-keratin). Possible mechanisms for this exceptional phenomenon are discussed.     

Schwannoma-Like Pleomorphic Adenoma: A Case Report with Review of the Literature

Pleomorphic adenoma is a common benign salivary gland tumor, which represents about 66 % of benign neoplasms of the salivary glands. Although it can occur in any salivary gland, it is most frequently found in the parotid. Pleomorphic adenomas are renowned for their cytomorphological and architectural heterogeneity that are characterized by intermixed epithelial and mesenchymal-like components. We report a rare case of pleomorphic adenoma of the parotid gland with prevalent schwannoma-like features mimicking a benign schwannoma. Microscopically the tumor showed a prevalence (about 95 %) of schwannoma-like areas with focal (about 5 %) epithelial component with tubular organization. The tumor showed positive immunoexpression for cytokeratin, S-100 protein, and focal expression of p63, CD10 and smooth muscle actin. To the best of our knowledge only six cases of schwannoma-like pleomorphic adenoma have been reported in the literature. The differential diagnosis between this entity and neurogenic and myogenic tumors is discussed.