Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review.

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.

Peripubertal Presentation of Metastatic Testicular Mixed, Nonseminomatous Germ Cell Tumor.

Testicular tumors are relatively rare in children and those in prepubertal children tend to present with different histological types and behaviors than their postpubertal counterparts. The majority of these pre- and peripubertal testicular tumors tend to be benign and those that are malignant, tend to present at low stages, not generally requiring systemic treatment. Here we present a rare case of a peri-pubertal, mixed nonseminomatous germ cell tumor of the testes which was found to be widely metastatic at presentation, classifying as poor risk disease.

Placental Site Trophoblastic Tumor in Mediastinal Recurrence of Mixed Germ Cell Tumor of the Testis: Report of a Case and Review of the Literature.

We present a rare case of a 42-year-old man diagnosed with a placental site trophoblastic tumor in combination with teratoma in a mediastinal recurrence of a testicular germ cell tumor post-orchiectomy and chemotherapy. To the best of our knowledge, this is the eighth case of placental site trophoblastic tumor in a male reported so far in the English literature. The purpose of this case report is to add data to the existing literature, review the literature, discuss the differential diagnoses with emphasis on morphologic and immunohistochemical differences between trophoblastic tumors, and highlight the management implications of a correct diagnosis.

Mixed Adeno-Neuroendocrine Neoplasms: Two Cases, One Institution.

Epithelial tumors with neuroendocrine and nonendocrine components constitute the rare yet aggressive entity of neoplasms of the gastro-entero-pancreatic tract. These tumors were first named "mixed adeno-neuroendocrine carcinomas" (MANECs) by the World Health Organization in 2010 and in 2017 renamed "mixed neuroendocrine non-neuroendocrine neoplasms" (MiNENs). Combined adenocarcinoma and neuroendocrine carcinoma neoplasms are a rare occurrence within the gastrointestinal tract. In this report, we describe two separate cases of mixed rectal adeno-neuroendocrine carcinomas and their treatment. We describe two cases at one institution of mixed neuroendocrine non-neuroendocrine rectal neoplasms. Given the rarity of diagnosis and inconsistencies in both nomenclature and treatment recommendations in the literature, mixed adeno-neuroendocrine carcinoma epidemiology and prognosis are not yet fully understood. Future prospective trials with a focus in management of MiNENs will offer valuable insight into these rare mixed carcinomas.

[Clinicopathological features of mixed cervical carcinoma with adenoid cystic pattern].

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular characteristics, differential diagnosis, clinical treatment and prognosis of mixed carcinoma of cervix with adenoid cystic pattern. Methods: Three cases of mixed cervical carcinoma with adenoid cystic pattern were collected at the Affiliated Hospital of Xuzhou University Medical School from 2018 to 2021.The clinicopathological characteristics were analyzed, immunohistochemistry (IHC) and in situ hybridization (ISH) were performed. The related literature was reviewed. Results: The three patients were postmenopausal women with a median age of 74.7 years. The clinical symptom was vaginal bleeding without obvious causes. One case was an endophytic tumor, and the others were exophytic. The median diameter of the three cases was 3.3 cm. Two patients underwent hysterectomy, the tumors infiltrated the external 1/3 and middle 1/3 of the cervix respectively. All the lymph nodes were negative. One patient had a previous biopsy. Microscopically, all three tumors were characterized by a cribriform structure, which were filled with basophilic myxoid substance and surrounded by tubules lined by two layers of cells. The tumor cells had scanty cytoplasm and showed the characteristics of cervical basal-like cells. All three cases were accompanied by high-grade squamous intraepithelial lesions and squamous cell carcinoma, and one also showed a non-specific spindle cell sarcomatoid component. Within the double-layered epithelial structure, the outer epithelium was positive for p63, CD117, p16INK4a (clone E6H4) and MYB protein and negative for S-100 by IHC. The combined positive score of PD-L1 (clone 22C3) was less than 1 in all three cases. Human papillomavirus (HPV) types 16 and 18 were detected in one patient preoperatively, while high-risk HPV were positive in the other two patients by RNAscope ISH postoperatively. None of the three cases showed MYB gene rearrangement by FISH. The mean follow-up time was 23.3 months (36, 28 and 6 months, respectively). Two patients underwent hysterectomy and radiotherapy survived without disease. One patient survived with tumor just by radiotherapy and drug therapy. Conclusions: Mixed cervical carcinoma with adenoid cystic pattern is extremely rare. It is a high-grade malignancy with poor prognosis. The tumor is associated with high-risk HPV infection, without MYB gene rearrangement, and with low PD-L1 immunoreactivity. Radical surgery combined with radiotherapy and chemotherapy is the mainstay of treatment at present.

Pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline BRCA2 mutation: a case report.

Loss of function in the BRCA2 gene exacerbates ovarian, breast, and pancreatic ductal cancer risk. Despite being implicated in the pancreatic ductal epithelium carcinogenesis, the involvement of a germline BRCA2 mutation in acinar and endocrine cells is less reported. A 45-year-old woman with a history of breast cancer was referred to our hospital for a detailed examination of epigastric pain. Her father had pancreatic cancer, and her paternal aunt had a history of breast cancer. Contrast-enhanced computed tomography revealed a round tumor with a contrast effect in the pancreatic head. The patient underwent pancreaticoduodenectomy, and postoperative pathology and genetic testing revealed amphicrine-type mixed acinar-neuroendocrine carcinoma with a germline BRCA2 mutation. Recent studies have reported the BRCA2 mutation in genome sequencing of pancreatic acinar cell carcinoma and neuroendocrine tumor; perhaps, genetic testing for the BRCA2 mutation is feasible for patients with mixed neuroendocrine-non-neuroendocrine neoplasm.

Malignant mixed tumour of the parotid gland in a preterm neonate with cytomegalovirus infection.

A young pregnant woman presented to the emergency department with acute lower abdominal pain. The ultrasound examination showed not only a viable fetus with a gestational age of 24 weeks but also a heteroechoic mass of about 7×7 cm involving parts of the face. The patient was found to be in active labour with rapid progression, and she gave birth to a dead female neonate. The autopsy showed a large malignant mixed tumour of the left parotid gland and revealed infection with cytomegalovirus. To our knowledge, this is the first reported case of a malignant mixed tumour of salivary glands in fetuses.

Rectal mixed adenoneuroendocrine carcinoma: Case report.

RATIONALE: Colorectal mixed neuroendocrine-nonneuroendocrine neoplasms constitute a rare group of gastrointestinal tumors composed by both neuroendocrine and nonneuroendocrine components. Nondiagnostic macroscopic features, specific histological features, and poor awareness of the disease are responsible for the underestimated incidence and conflicting data available. Due to lack of randomized clinical trials and validated clinical guidelines, diagnostic and therapeutic approach are based on the standard of care for pure colorectal neuroendocrine carcinomas or adenocarcinomas. PATIENT CONCERNS: A 76-year-old caucasian male, without relevant medical or familial history, presented a positive faecal occult blood test during colorectal cancer screening. DIAGNOSIS: Total colonoscopy identified a rectal lesion with biopsy showing a moderate rectal adenocarcinoma staged as cT2N0M0. INTERVENTIONS: Anterior resection of the rectum with right ileostomy followed by local radiotherapy with radio-sensitising chemotherapy and adjuvant chemotherapy with capecitabine 1000 mg bid plus oxaliplatin 130 mg/m2. Due to chronic nodular pulmonary aspergillosis and chemotherapy induced immunosuppression patient was on 400 mg/daily of oral voriconazole. OUTCOMES: Overall survival of 15 months after progression under first line treatment and under palliative chemotherapy with platinum plus etoposide regimen. LESSONS: The reported case illustrates the challenge associated to the management of mixed neuroendocrine-nonneuroendocrine carcinomas due to lack of validated guidelines and scientific evidence. From diagnosis and staging to treatment, all steps must be tailored to individual clinical and histological features.

Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation.

Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. Electronic medical records were reviewed for clinical history, imaging findings, laboratory results, and follow-up. Pathology slides, immunohistochemistry, and ancillary studies were reviewed. There were two females and two males with age ranging from 52 to 74 years. There was one amphicrine carcinoma with tumor cells simultaneously demonstrating both hepatocellular and neuroendocrine differentiation, one mixed hepatocellular-neuroendocrine carcinoma (NEC) with hepatocellular component intermingled with neuroendocrine component, one small cell NEC, and one well-differentiated neuroendocrine tumor. Next- generation sequencing of the mixed hepatocellular-NEC and small cell NEC showed molecular/genetic alterations commonly seen in hepatocellular carcinoma (HCC). All four cases arose in a background of cirrhosis. Primary hepatic neoplasms arising in cirrhotic livers can have a spectrum of neuroendocrine differentiation. Presence of a NEC component may be an indicator of aggressiveness. In addition, primary hepatic carcinomas with neuroendocrine differentiation likely share the same molecular pathways as HCC.

Survival and prognostic factors of salivary gland malignant mixed tumor-not otherwise specified: A population-based analysis.

OBJECTIVE: Malignant mixed tumors of the salivary gland are a group of neoplasms comprised of carcinoma-ex-pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. An alternative classification, malignant mixed tumor-not otherwise (MMT-NOS), is a diagnosis of exclusion for neoplasms that do not fit the previous histologically profiled subtypes. The objective was to provide a comprehensive assessment of MMT-NOS and determine prognostic factors. METHODS: This retrospective cohort study queried the Surveillance, Epidemiology, and End Results database for patient and tumor characteristics of US patients with MMT-NOS of the major salivary glands from 1973 to 2016. Kaplan-Meier and Cox regression analysis were performed to determine 5-year survival and prognostic factors. RESULTS: 434 patients were identified with a mean age at diagnosis of 61.5 years. The majority of neoplasms were high grade and stage (70.8% grade III/IV; 63.8% stage III/IV). Extraparenchymal extension (40.6%) and lymph node involvement (28.5%) were common; distant metastases (2.4%) were rare. Treatment included surgery (93.0%), radiation (51.6%), and chemotherapy (10.4%). Facial nerve sacrifice was common (50.8%). Median survival was 66.5 months. 5-year overall and disease-specific survival were 65.7% and 83.0%, respectively. In multivariate analysis, nodal involvement (HR 7.0; P < 0.001), surgery-radiation-chemotherapy (HR 6.1; P = 0.02), extraparenchymal extension (HR 2.50; P = 0.04), and tumor size >4 cm (HR 1.3; P = 0.03) were prognostic factors. CONCLUSION: Despite high stage and grade at diagnosis, MMT-NOS portends a good 5-year prognosis and low rate of distant metastasis. Prognostic factors were nodal involvement, tumor size, and extraparenchymal extension.

An atypical chondroid syringoma with malignant degeneration: Utility of comparative genomic hybridization in confirming the diagnosis.

Chondroid syringoma (CS) represents the cutaneous counterpart of mixed tumor (pleomorphic adenoma) of salivary glands. Definitive diagnosis is made on histopathology and is based on the presence of characteristic epithelial and stromal components. We report a case of an atypical CS arising on the extremity of an elderly male patient. Histomorphologic features of necrosis and cellular atypia raised suspicion for malignant degeneration, an exceptionally rare circumstance in this context. To further support the diagnosis of malignancy, array comparative genomic hybridization was performed from both low and higher grade areas of the tumor. Both regions demonstrated multiple copy number gains and losses, with additional loss of q7p (TP53), loss of 19p, and loss of heterozygosity on16q demonstrated in the more atypical foci. To our knowledge, this is the first case description of malignant degeneration of a CS with correlative microarray analysis. The findings in this case may prove useful in confirming the diagnosis in future ambiguous cases.

Malignant Mixed Germ Cell Tumors of the Ovary: An Analysis of 100 Cases Emphasizing the Frequency and Interrelationships of Their Tumor Types.

One hundred malignant mixed germ cell tumors of the ovary that occurred in patients 3 to 55 years (mean: 20 y) of age are described. The clinical presentation was usually that of any highly malignant tumor of the ovary (abdominal pain and distension), but rarely (3 cases) endocrine manifestations were present. The tumors were usually unilateral (96%), ranged from 4 to 38 cm (mean: 16 cm), and were uniformly solid or, more often, solid and cystic; occasionally the typical appearance of dysgerminoma could be appreciated. The most common tumor type was yolk sac tumor (91%), followed by dysgerminoma (61%), immature teratoma (58%), embryonal carcinoma (38%), and choriocarcinoma (11%). A variety of admixtures were encountered; dysgerminoma and yolk sac tumor was the most common combination (25% of the tumors) with the 2 components often being sharply demarcated. Immature teratoma and yolk sac tumor was the next most common pairing (20%) followed by yolk sac tumor and embryonal carcinoma, with or without immature teratoma (16%). Tumors with a choriocarcinoma component had the most varied combinations of tumor types. Embryoid bodies were seen in 21% of the tumors, most often as fragmented forms arranged in a nodular manner with yolk sac tumor and/or embryonal carcinoma; uncommonly they occurred singly or in clusters. Numerous confluent well-formed embryoid bodies (polyembryoma) were prominent in 2 tumors. Three tumors had a focal diffuse embryoma pattern. The specific tumor types showed the known diverse spectrum of microscopic appearances, but the frequent haphazard arrangement of 2 or more subtypes often resulted in complex morphology. Overgrowth of another neoplastic component, most often primitive neuroectodermal tumor, occurred in 10% of the tumors further complicating the histologic picture. This is the largest series of ovarian malignant mixed germ cell tumors reported and details their characteristics including associations of their subtypes and the frequent apparent role of embryoid bodies in giving rise to yolk sac tumor and embryonal carcinoma components.

The clinical profiles, management, and prognostic factors of biliary mixed neuroendocrine nonneuroendocrine neoplasms: A systematic review of the literature.

BACKGROUND: Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs. METHODS: A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan-Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression. RESULTS: Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time. CONCLUSION: Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.

Adenoma pleomorfo de la mama. A propósito de un caso / Pleomorphic adenoma of the breast. Apropos of a case

OBJETIVO: El adenoma pleomorfo es un tumor con una gran heterogenicidad arquitectural y citológica, de ahí su denominación como tumor mixto. Compuesto característicamente por células epiteliales y mioepiteliales con estroma mesenquimal, presenta un comportamiento benigno, siendo su localización habitual las glándulas salivares. La mama es una localización muy infrecuente para este tipo de tumores. CASO CLÍNICO: Presentamos el caso clínico de una paciente de 76 años sin antecedentes de patología mamaria, valorada en consultas externas de cirugía por una secreción unilateral de aspecto serosanguinolento desde la mama derecha, asociada a un nódulo de unos 2cm de diámetro mayor. Tras completar su estudio, se decide exéresis de la tumoración, obteniendo como resultado en la anatomía patológica una tumoración heterogénea con predominio de células miopiteliales; descripción compatible con un adenoma pleomorfo. DISCUSIÓN: El adenoma pleomorfo de la mama, es una tumoración epitelial benigna que tiene un patrón histológico similar al del tumor de las glándulas salivares. Los rasgos histológicos más importantes es la metaplasia ósea y mixocondroide, junto con presencia de calcificaciones, tejido epitelial (con o sin diferenciación glandular), y tejido mioepitelial; siendo esta gran variedad estructural lo que le caracteriza. Hay que realizar un diagnóstico diferencial con patología maligna a la cual asemeja. Se presenta de forma poco frecuente a nivel mamario y suele ser una lesión bien delimitada y solitaria, elastica y no adherida. Pese a su comportamiento benigno (no ha presentado en ninguno de los casos documentados metástasis a distancia) el tratamiento es quirúrgico, asegurando buenos margenes de resección para evitar recidivas

OBJECTIVE: Pleomorphic adenoma shows wide architectural and cytological heterogeneity and is consequently classified as a mixed tumour. These benign adenomas are characteristically composed of epithelial and myoepithelial cells with mesenchymal stroma and are usually located in the salivary glands. Localisation in the breast is extremely infrequent for this type of tumour. CASE REPORT: We report the case of a 76-year-old female patient with no prior history of breast disease who was assessed in the surgery outpatient clinic for unilateral serosanguinous secretion from the right breast associated with a nodule of approximately 2cm in diameter. After workup, it was decided to extirpate the tumour. Histological findings indicated a heterogeneous tumour with a predominance of myoepithelial cells, compatible with pleomorphic adenoma. DISCUSSION: Pleomorphic adenoma of the breast is a benign epithelial tumour whose histological pattern is similar to that of pleomorphic adenoma of the salivary glands. The most important histological features are osseous and myxochondroid metaplasia, together with the presence of calcifications, epithelial tissue (with or without glandular differentiation) and myoepithelial tissue. This wide structural variety is what characterises these tumours. The differential diagnosis should be performed with malignant disease, which these adenomas frequently mimic. Pleomorphic adenomas are very infrequent in the breast and are usually well-demarcated, solitary, elastic and non-adherent tumours. Despite their benign behaviour (there have been no reported cases of distant metastases), treatment is surgical, with good resection margins to avoid recurrences

False-positive staining of thyroglobulin distinguished from mixed medullary and follicular thyroid carcinoma by duplex in situ hybridization.

Medullary thyroid carcinoma (MTC) may mimic mixed medullary and follicular thyroid carcinoma (MMFTC). MTC originates from para-follicular cells, while MMFTC is an uncommon tumor characterized by coexistence of follicular and para-follicular cell-derived tumor populations. A 35-year-old woman was diagnosed with MTC but showed a hot nodule in thyroid scintigraphy. The tumor included diffusely-spread follicular lesions within it, which were immunostained with thyroglobulin and calcitonin. Immunofluorescence showed the presence of several tumor cells that were double-stained with thyroglobulin and calcitonin. To clarify whether or not the tumor was MMFTC, we used duplex in situ hybridization (ISH). Thyroglobulin and calcitonin-related polypeptide alpha mRNA were not expressed together in a single cell, so we suspected false-positive staining of tumor cells with thyroglobulin. To make comparisons with other follicular lesions in MTC, we searched our hospital database. Five cases within a ten-year period had been pathologically diagnosed as MTC. All had follicular lesions in the tumor, but unlike the other case, they were peripherally localized. Dual differentiation into follicular or para-follicular tumor cells was not indicated by either immunofluorescence or duplex ISH. Compared with the case suspected to be MMFTC, there was only mild invasion of tumor cells into the follicular epithelium. The extent of follicular lesions and invasiveness of tumor cells may be associated with pseudo-staining of thyroglobulin in MTC. Duplex ISH can distinguish MTC that are stained with thyroglobulin from MMFTC.