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1.  Salivary duct carcinoma of the parotid gland 
Salivary duct carcinoma of the parotid gland is an uncommon tumor, highly aggressive. About 200 cases have been reported in the English literature. Pathomorphologically, these tumors showed great similarities to ductal carcinoma of the female breast, which is why they described this tumor as “salivary duct carcinoma.” The authors describe a new case of salivary duct carcinoma of the parotid gland. We present the case of a 50-year-old patient with progressive facial paralysis. The MRI examination of the head showed two ill-defined formations. A malignant tumor was strongly suspected, so that a total left parotidectomy with excision of the adjacent facial nerve and left lymph node dissection was performed. Microscopic examination concluded to a salivary duct carcinoma of the left parotid gland negative with Her2/neu antibody with lymph node metastasis. There were no recurrences or metastases within 3 years of follow-up. Salivary duct carcinoma of the parotid gland is a rare tumor with an aggressive behavior. This is due to its propensity to infiltrate distant organs. The diagnosis is based on microscopic examination. Treatment modalities are non-consensual, but some authors advocate the necessity of aggressive approach, especially in tumors negative with Heur2/neu antibody. This is due to the fact that the overexpression of this antigen was reported to be associated with a poor prognosis.
PMCID: PMC3303509  PMID: 22434951
Parotid gland; salivary duct carcinoma; treatment
2.  Metastatic hepatocellular carcinoma to the parotid gland: Case report and review of the literature 
Hepatocellular carcinoma, the most frequent primary hepatic tumor, metastasizes in more than 50% of cases. However, parotid gland metastatic HCCs are very uncommon. We report a patient in whom the finding of a left parotid mass revealed metastatic HCC.
A thirty-six-year-old male presented with a round palpable left neck mass that persisted for 3 months. He had received right hemihepatectomy for hepatocellular carcinoma (HCC). Preoperative evaluation revealed a benign tumor of the parotid gland. We performed superficial parotidectomy. Metastatic hepatocellular carcinoma of the parotid gland was diagnosed.
Although HCC metastases to the oral cavity have been reported, to date, only 4 cases HCC metastasis to the parotid gland have been reported. Although clinicians and cytopathologists alike both agree that salivary gland fine needle aspiration biopies (FNABs) are highly useful and safe diagnostic alternatives to biopsies and resections, we believe that in specific clinical situations, awareness of potential diagnostic pitfalls in salivary gland FNAB is a necessary part of the microscopic interpretations of these lesions.
Although rare, since HCC can metastasize to the parotid gland, high suspicion should be maintained in a patient presenting with a parotid mass with a history of HCC. In addition, since potential diagnostic pitfalls in salivary gland fine-needle aspiration (FNA) biopsies exist, incisional or excisional biopsy may be necessary for definite diagnosis of metastatic HCC to the parotid gland.
PMCID: PMC3537927  PMID: 23123420
HCC, hepatocellular carcinoma; FNA, fine-needle aspiration; Metastatic hepatocellular carcinoma; Parotid gland; Fine-needle aspiration
3.  Postoperative Radiation Therapy for Parotid Mucoepidermoid Carcinoma 
Salivary gland cancers are rare and represent approximately 5% of all head and neck cancers and only 0.3% of all malignancies. The majority (75%) of salivary gland tumors occur in the parotid gland, and while benign lesions are more common, mucoepidermoid carcinoma (MEC) makes up 40–50% of malignant parotid gland tumors. No randomized controlled trials exist regarding the role of adjuvant radiation for patients who undergo surgical resection of low-grade MECs. Herein, we report two cases of successful postoperative radiation therapy in low-grade, pT2N0 MEC of the parotid gland. The role of adjuvant radiation therapy for patients with MEC of the parotid gland is based on data from institution reviews and lacks data from randomized controlled trials. Per our review of the literature, the pathological findings of positive surgical margins and/or perineural invasion in two patients with low-grade MEC of the parotid gland warranted adjuvant radiation for improved local control after partial parotidectomy. Both patients tolerated postoperative radiation therapy with only mild side effects and, at last follow-up, five years after completion of therapy, had no clinical or radiographic evidence of either local recurrence or distant metastasis.
PMCID: PMC4279126  PMID: 25580323
4.  Metastatic Hepatocellular Carcinoma to Parotid Glands 
Patient: Male, 66
Final Diagnosis: Hepatocellular carcinoma
Symptoms: Abdominal distension • painful right facial swelling • weight loss
Medication: —
Clinical Procedure: —
Specialty: —
Rare disease
Hepatocellular carcinoma is a common cancer, but it rarely metastasizes to the salivary glands. A review of the literature revealed only 5 reported cases of hepatocellular carcinoma metastatic to parotid glands. We here report an additional case of this rare association.
Case Report:
A 66-year-old male with a background of type 2 diabetes mellitus and post-alcoholic decompensated liver cirrhosis presented with a progressively enlarging painful right facial swelling for 2 months that was eventually found to be due to hepatocellular carcinoma metastatic to the right parotid gland. Fine needle aspiration from the right parotid showed sheets and single malignant cells that were interpreted as carcinoma not otherwise specific. However, biopsy showed metastatic hepatocellular carcinoma into the right parotid gland.
We report an additional case of the rare metastasis of hepatocellular carcinoma to the parotid glands. It should therefore be considered in a patient with decompensated liver cirrhosis presenting with a parotid swelling. Furthermore, the present case demonstrates the importance of the tissue biopsy for obtaining an accurate final diagnosis.
PMCID: PMC4144943  PMID: 25129420
Carcinoma, Hepatocellular; Gastrointestinal Neoplasms; Neoplasm Metastasis; Neoplasm Metastasis; Parotid Gland
5.  Primary parotid gland lymphoma: a case report 
Mucosa associated lymphoid tissue lymphomas are the most common lymphomas of the salivary glands. The benign lymphoepithelial lesion is also a lymphoproliferative disease that develops in the parotid gland. In the present case report, we describe one case of benign lymphoepithelial lesion with a subsequent low transformation to grade mucosa associated lymphoid tissue lymphoma appearing as a cystic mass in the parotid gland.
Case presentation
A 78-year-old Caucasian female smoker was referred to our clinic with a non-tender left facial swelling that had been present for approximately three years. The patient underwent resection of the left parotid gland with preservation of the left facial nerve through a preauricular incision. The pathology report was consistent with a low-grade marginal-zone B-cell non-Hodgkin lymphoma (mucosa associated lymphoid tissue lymphoma) following benign lymphoepithelial lesion of the gland.
Salivary gland mucosa associated lymphoid tissue lymphoma should be considered in the differential diagnosis of cystic or bilateral salivary gland lesions. Parotidectomy is recommended in order to treat the tumor and to ensure histological diagnosis for further follow-up planning. Radiotherapy and chemotherapy should be considered in association with surgery in disseminated forms or after removal.
PMCID: PMC3170354  PMID: 21843311
6.  DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer 
PLoS Medicine  2009;6(5):e1000068.
Ann Killary and colleagues describe a new gene that is genetically altered in breast tumors, and that may provide a new breast cancer prognostic marker.
Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium–associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.
Methods and Findings
Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young female breast cancer patients with a 20-year follow-up indicated that in early-onset breast cancer, DEAR1 expression serves as an independent predictor of local recurrence-free survival and correlates significantly with strong family history of breast cancer and the triple-negative phenotype (ER−, PR−, HER-2−) of breast cancers with poor prognosis.
Our data provide compelling evidence for the genetic alteration and loss of expression of DEAR1 in breast cancer, for the functional role of DEAR1 in the dominant regulation of acinar morphogenesis in 3D culture, and for the potential utility of an immunohistochemical assay for DEAR1 expression as an independent prognostic marker for stratification of early-onset disease.
Editors' Summary
Each year, more than one million women discover that they have breast cancer. This type of cancer begins when cells in the breast that line the milk-producing glands or the tubes that take the milk to the nipples (glandular and ductal epithelial cells, respectively) acquire genetic changes that allow them to grow uncontrollably and to move around the body (metastasize). The uncontrolled division leads to the formation of a lump that can be detected by mammography (a breast X-ray) or by manual breast examination. Breast cancer is treated by surgical removal of the lump or, if the cancer has started to spread, by removal of the whole breast (mastectomy). Surgery is usually followed by radiotherapy or chemotherapy. These “adjuvant” therapies are designed to kill any remaining cancer cells but can make patients very ill. Generally speaking, the outlook for women with breast cancer is good. In the US, for example, nearly 90% of affected women are still alive five years after their diagnosis.
Why Was This Study Done?
Although breast cancer is usually diagnosed in women in their 50s or 60s, some women develop breast cancer much earlier. In these women, the disease is often very aggressive. Compared to older women, young women with breast cancer have a lower overall survival rate and their cancer is more likely to recur locally or to metastasize. It would be useful to be able to recognize those younger women at the greatest risk of cancer recurrence so that they could be offered intensive surveillance and adjuvant therapy; those women at a lower risk could have gentler treatments. To achieve this type of “stratification,” the genetic changes that underlie breast cancer in young women need to be identified. In this study, the researchers discover a gene that is genetically altered (by mutations or deletion) in early-onset breast cancer and then investigate whether its expression can predict outcomes in women with this disease.
What Did the Researchers Do and Find?
The researchers used “suppression subtractive hybridization” to identify a new gene in a region of human Chromosome 1 where loss of heterozygosity (LOH; a genetic alteration associated with cancer development) frequently occurs. They called the gene DEAR1 (ductal epithelium-associated RING Chromosome 1) to indicate that it is expressed in ductal and glandular epithelial cells and encodes a “RING finger” protein (specifically, a subtype called a TRIM protein; RING finger proteins such as BRCA1 and BRCA2 have been implicated in early cancer development and in a large fraction of inherited breast cancers). DEAR1 expression was reduced or lost in several ductal carcinomas in situ (a local abnormality that can develop into breast cancer) and advanced breast cancers, the researchers report. Furthermore, many breast tumors carried DEAR1 missense mutations (genetic changes that interfere with the normal function of the DEAR1 protein) or had lost both copies of DEAR1 (the human genome contains two copies of most genes). To determine the function of DEAR1, the researchers replaced a normal copy of DEAR1 into a breast cancer cell that had a mutation in DEAR1. They then examined the growth of these genetically manipulated cells in special three-dimensional cultures. The breast cancer cells without DEAR1 grew rapidly without an organized structure while the breast cancer cells containing the introduced copy of DEAR1 formed structures that resembled normal breast acini (sac-like structures that secrete milk). In normal human mammary epithelial cells, the researchers silenced DEAR1 expression and also showed that without DEAR1, the normal mammary cells lost their ability to form proper acini. Finally, the researchers report that DEAR1 expression (detected “immunohistochemically”) was frequently lost in women who had had early-onset breast cancer and that the loss of DEAR1 expression correlated with reduced local recurrence-free survival, a strong family history of breast cancer and with a breast cancer subtype that has a poor outcome.
What Do These Findings Mean?
These findings indicate that genetic alteration and loss of expression of DEAR1 are common in breast cancer. Although laboratory experiments may not necessarily reflect what happens in people, the results from the three-dimensional culture of breast epithelial cells suggest that DEAR1 may regulate the normal acinar structure of the breast. Consequently, loss of DEAR1 expression could be an early event in breast cancer development. Most importantly, the correlation between DEAR1 expression and both local recurrence in early-onset breast cancer and a breast cancer subtype with a poor outcome suggests that it might be possible to use DEAR1 expression to identify women with early-onset breast cancer who have an increased risk of local recurrence so that they get the most appropriate treatment for their cancer.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Senthil Muthuswamy
The US National Cancer Institute provides detailed information for patients and health professionals on all aspects of breast cancer, including information on genetic alterations in breast cancer (in English and Spanish)
The MedlinePlus Encyclopedia provides information for patients about breast cancer; MedlinePlus also provides links to many other breast cancer resources (in English and Spanish)
The UK charities Cancerbackup (now merged with MacMillan Cancer Support) and Cancer Research UK also provide detailed information about breast cancer
PMCID: PMC2673042  PMID: 19536326
7.  Parotid gland metastasis of lung cancer: a case report 
Parotid gland metastasis in lung cancer is extremely rare, very few cases have been reported.
Case presentation
We report on the case of a 61-year-old Chinese male patient who presented with parotid swelling metastasizing from advanced lung cancer. We therefore performed an operation of partial parotidectomy with preservation of the facial nerve and advised the patient receive chemotherapy, however, the patient died four months later.
Although it is extremely rare, a potential metastasis of lung cancer should not be ignored in the diagnosis of parotid tumor. Preoperative routine examination, such as a chest X-ray and lung computational tomography scan, may play an important role in differential diagnosis. The management of the metastatic tumor to the parotid gland was controversial however, despite combined treatment modalities, long-term survival was not attained.
PMCID: PMC4004509  PMID: 24758587
Parotid gland tumor; Small cell cancer; Lung cancer; Metastasis
8.  Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report 
Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.
Case presentation
A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.
This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.
PMCID: PMC2075501  PMID: 17848197
9.  Extended parotidectomy 
Malignant tumours of the parotid gland represent a group of relatively rare lesions. The medical records of 363 patients with parotid swelling treated between 1974 and 2003 at the “G. Ferreri” Department of Otorhinolaryngology, “La Sapienza” University in Rome were retrospectively analysed. Clinical presentation, pre-operative investigations, surgical procedure, histopathology report, post-operative complications, and the oncological results of 19 patients who underwent extended radical parotidectomy for malignant neoplasm of the parotid gland are discussed. Extended radical parotidectomy, reserved for neoplasms in an advanced stage, involves the removal of the entire parotid gland, with sacrifice of the facial nerve and the resection en bloc of the adjacent structures affected by neoplastic infiltration, such as the temporal bone, the mandibular bone, the skin, blood vessels and nerves. In addition to this surgical treatment, a cycle of adjuvant radiotherapy is also necessary. The overall rate of survival at 10 years depends mainly on the histological characteristics of the tumour, and, in this series, is reported to be approximately 58%. These data indicate that total extended radical parotidectomy combined with post-operative radiotherapy, represents the best therapeutic approach with regard both to quality of life and life expectancy, in patients with an advanced stage of malignant neoplasm of the parotid gland.
PMCID: PMC2639865  PMID: 16450772
Parotid gland; Malignant tumours; Treatment; Extended parotidectomy
10.  Case report: anti-hormonal therapy in the treatment of ductal carcinoma of the parotid gland 
BMC Cancer  2014;14(1):701.
Ductal carcinomas of the parotid gland are rare, highly aggressive, have a poor prognosis and are histologically similar to Ductal Breast Cancer. We report what we believe to be the first case in literature of metastatic salivary duct carcinoma (SDC) of the parotid gland with objective response to tamoxifen and aromatase inhibitors, achieving a long-term stability of disease with no associated toxicity.
Case presentation
A 70-year-old female was referred to our institution for treatment of a painless nodular lesion in the scalp, localized in the frontal region of the cranium. A biopsy was taken and tested positive for metastatic ductal carcinoma. On PET CT hypermetabolic nodules were localized in the left parotid gland (11 mm), right parotid gland (10 and 12 mm), submandibular node (11 mm) and left cervical node (10 mm). A salivary ductal carcinoma was considered to be the primary tumor. The patient was subsequently started on tamoxifen, with a complete response from the scalp nodule and left parotid nodule, while the right parotid nodule demonstrated a partial response that maintained stable for 2 years until progression. Anastrazol was chosen as the next line of treatment, achieving 6 more months of stable disease. As a pseudo-adjuvant treatment, surgical resection of the right parotid lesion was performed and helped achieve two years of disease stability.
Estrogen receptor antagonists such as tamoxifen or aromatase inhibitors may represent a target for the establishment of a safe alternative and novel therapy for SDC, however more accurate data obtained from larger studies are required.
PMCID: PMC4190344  PMID: 25249211
Tamoxifen; Salivary gland; Ductal carcinoma; Estrogen receptor antagonist
11.  Carcinoma ex pleomorphic adenoma: Diagnostic dilemma and treatment protocol 
Indian Journal of Dentistry  2014;5(3):157-160.
Carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. The entity is difficult to diagnose preoperatively. Pathological assessment is the gold standard for making the diagnosis. Treatment for CXPA often involves an ablative surgical procedure, which may be followed by radiotherapy. We report a case of a 65-year-old lady with a history of recurrent swelling in the left preauricular region and a history of surgery 10 years back, in the same region. Preoperatively, a diagnosis of pleomorphic adenoma of the parotid gland metastasizing to the cervical lymph node was made, but postoperatively it was reported as CXPA adenoma of the parotid gland. A radical parotidectomy involving en bloc resection of the facial nerve along with deep and superficial lobes of the parotid was performed followed by radiotherapy. The fact that pleomorphic adenomas are classified as benign tumors should not overshadow the wide range of biological behaviors associated with these tumors. On account of the potential for malignant transformation, surgical treatment must be properly performed. Surgery followed by radiotherapy should be considered as the standard care for a patient with carcinoma ex pleomorphic adenoma.
PMCID: PMC4213878  PMID: 25565746
Carcinoma ex pleomorphic adenoma; parotidectomy; parotid carcinoma
12.  Metabolic Imaging Biomarkers of Post-Radiotherapy Xerostomia 
Xerostomia is a major complication of head and neck radiotherapy. Available xerostomia measures remain flawed. FDG-PET/CT is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-radiotherapy xerostomia.
Methods and Materials
Ninety-eight locally advanced head and neck cancer patients receiving definitive radiotherapy underwent baseline and post-radiotherapy FDG-PET/CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled onto a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre/post-RT SUVs for all voxels contained within parotid gland regions-of-interest were deformably registered.
Average whole gland or voxel-by-voxel models incorporating parotid DMet (defined as the pre-treatment parotid SUV weighted by dose) accurately predicted post-treatment changes in parotid FDG uptake (e.g. fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by post-treatment salivary output (p < 0.01) and RTOG/EORTC xerostomia scores (p < 0.01).
In this pilot series, loss of parotid FDG uptake strongly associates with acute clinical post-radiotherapy parotid toxicity. DMet may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET/CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.
PMCID: PMC4271834  PMID: 22658215
Radiotherapy; IMRT; PET/CT; imaging; biomarker; normal tissue toxicity; xerostomia
13.  Adenoid cystic carcinoma of the parotid metastasizing to liver: case report 
BMC Cancer  2004;4:41.
Adenoid cystic carcinoma is a rare malignant parotid tumor. Metastasis can occur even a decade or more after initial treatment of the primary.
Case presentation
We report a 60 year old female patient who presented with adenoid cystic carcinoma of the parotid gland. She underwent a total conservative parotidectomy followed by adjuvant radiotherapy. While on follow up, patient developed multiple liver metastases which manifested three years later. Patient lived for another two years before she died of her disease.
Although distant metastases of adenoid cystic carcinoma develop frequently, isolated metastasis to liver is unusual. Even after manifestation of distant metastasis, patients can be expected to live for a number of years. Palliative chemotherapy can be considered in symptomatic cases while the usefulness of metastatectomy is controversial.
PMCID: PMC509249  PMID: 15285782
14.  Complete pathologic response of HER2-positive breast cancer liver metastasis with dual Anti-HER2 antagonism 
BMC Cancer  2014;14:242.
Although breast cancer frequently metastasizes to the bones and brain, rarely breast cancer patients may develop isolated liver metastasis. There is increasing data that anti-HER2 targeted therapy in conjunction with systemic chemotherapy may lead to increased rates of pathologic complete response in the primary breast cancer. However, little is known about its effects on metastatic liver disease.
Case presentation
We report the treatment of a 54-year-old female who was diagnosed with HER2-positive invasive ductal carcinoma and synchronous breast cancer liver metastasis (BCLM). The patient underwent eight cycles of standard docetaxel with two anti-HER2 targeted agents, trastuzumab and pertuzumab. Subsequent radiographic imaging demonstrated complete radiographic response in the primary lesion with an approximate 75% decrease in the liver metastasis. After informed consent the patient underwent modified radical mastectomy that revealed pathologic complete response. Re-staging demonstrated no new disease outside the liver and a left hepatectomy was performed for resection of BCLM. Final pathologic examination revealed no residual malignant cells in the liver specimen, indicating pathologic complete response. Herein, we discuss the anti-HER2 targeted agents trastuzumab and pertuzumab and review the data on dual HER2 antagonism for HER2-positive breast cancer and the role of surgical resection of BCLM.
The role of targeted agents for metastatic HER2-positive breast cancer is under active clinical trial investigation and we await the maturation of trial results and long-term survival data. Our results suggest that these agents may also be effective for producing considerable pathologic response in patients with BCLM.
PMCID: PMC3978138  PMID: 24708527
HER2-positive breast cancer; Targeted therapy; Breast cancer liver metastases; Trastuzumab; Pertuzumab; Complete pathologic response
15.  An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland 
Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.
PMCID: PMC3905163  PMID: 24456816
Carcinoma ex pleomorphic adenoma; Parotid tumours; Pleomorphic adenoma; Splenic metastases
16.  Somatostatin-receptor scintigraphy for staging and follow-up of patients with extraintestinal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type 
British Journal of Cancer  2001;85(10):1462-1466.
The majority of lymphomas of the mucosa-associated lymphoid tissue (MALT)-type arise in the stomach, but extragastric locations are also frequently encountered. Due to previous results indicating that somatostatin receptor (SSTR)-expression distinguishes between gastric and extragastric MALT-type lymphoma, we have initiated a study to evaluate the role of SSTR-scintigraphy for staging and follow-up of patients with extragastric manifestations of MALT-type lymphoma. A total of 30 consecutive patients, including 24 with primary extragastric MALT-type lymphoma, 5 patients with dissemination to extragastric sites (including colon, lung, parotid, ocular adnexa and breast) following an initial gastric MALT-lymphoma and one patient with spread to stomach, lung and lymph nodes following parotid lymphoma were prospectively studied. All patients had histologically verified MALT-type lymphoma: 2 patients had lymphoma presenting in the lung, 9 in the ocular adnexa, 7 had lymphomas in the parotid, 2 patients had disease located in the breast, 3 patients had lymph-node relapse following MALT-type lymphoma of the parotid, the lacrimal gland and the thyroid, and 1 had primary MALT-lymphoma of the liver. All patients underwent SSTR-scintigraphy using 111In-DTPA-D-Phe1-Octreotide (111In-OCT) before initiation of therapy, while 13 also had a second scan after treatment. The results of gamma camera imaging were compared to conventional staging. No positive scans could be obtained in patients with dissemination following gastric lymphoma, while all patients with primary extragastric lymphoma had positive scans at the site of histologically documented involvement before initiation of therapy. In addition, also the patient with secondary spread to stomach, lung and lymph nodes was positive in all documented lymphoma sites. In one patient, focal tracer uptake in projection to the maxillary sinus was documented, which was bioptically verified as inflammation. In the scans performed after therapy, focal tracer accumulation in the left orbit indicated persistance of disease following irradiation in one patient with otherwise negative work-up, which was verified by MRI and biopsy 6 months later. In another patient, a positive scan indicated disease relapse in the lacrimal gland 9 months before clinical verification by means of ultrasound. In one patient, a focus not present in the pretherapeutic scan was found in the ethmoidal sinus, corresponding to a hyperplastic polyp. Both SST-scan as well as CT indicated disease persistance in one case, while negative scans corresponding to complete remission as judged by conventional staging were obtained following therapy in the remaining patients, and absence of relapse has been confirmed for a median follow-up of 2 years. These results indicate that 111In-OCT is an excellent tool for staging and non-invasive therapy-monitoring in extragastric MALT-type lymphomas. These data further confirm our initial finding that gastric MALT-type lymphomas do not express relevant amounts of respective SSTR, and that SSTR-scanning is able to distinguish between gastric vs extragastric origin of MALT-type lymphoma irrespective of the site of presentation.© 2001 Cancer Research Campaign
PMCID: PMC2363931  PMID: 11720429
somatostatin; extraintestinal MALT-lymphoma; scintigraphy
17.  An audit of surgery of the parotid gland. 
The management of patients undergoing 50 surgical procedures to the parotid gland was reviewed. The overall accuracy of fine needle aspiration cytology was 87%, false-positive and false-negative rates for malignant disease both being 4%. The sensitivity, specificity and accuracy of fine needle cytology for malignant parotid tumours was 66%, 95%, and 91%, respectively, that of benign tumours (pleomorphic adenoma or Warthin's tumour) being 88%, 83% and 87%, respectively. Sensitivity, specificity and accuracy for the remaining (principally inflammatory) parotid diseases was 100%, 95% and 96%, respectively. The predictive value of a positive test for malignant tumours, benign tumours and inflammatory conditions was 66%, 94% and 75%, respectively. The negative predictive value for these conditions was 95%, 71% and 100%, respectively. Facial nerve weakness after parotidectomy occurred in three patients (8.8%), being permanent in two cases (both malignant). Although Frey's syndrome was not recorded in any of the notes, careful follow-up revealed two cases (6%). To date there have been no local recurrences after excision of either benign or primary malignant parotid masses. One patient with squamous cell carcinoma metastatic to the parotid gland died, despite block dissection of the neck and radiotherapy. This small series with a limited follow-up suggests that diseases of the parotid gland can be managed by general surgeons with an interest in this field. Although fine needle aspiration and ultrasonic scan may be helpful, the decision to operate should be made on clinical grounds.
PMCID: PMC2502101  PMID: 7598416
18.  Receptor-Defined Subtypes of Breast Cancer in Indigenous Populations in Africa: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(9):e1001720.
In a systematic review and meta-analysis, Isabel dos Santos Silva and colleagues estimate the prevalence of receptor-defined subtypes of breast cancer in North Africa and sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Breast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa.
Methods and Findings
Medline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n = 12,284 women with breast cancer) and 26 from sub-Saharan Africa (n = 4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%–17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%–17%) lower for those with ≥40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56–0.62) and 0.21 (0.17–0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study.
The published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost.
Please see later in the article for the Editors' Summary
Editors' Summary
Breast cancer is the commonest female tumor in Africa and death rates from the disease in some African countries are among the highest in the world. Breast cancer begins when cells in the breast acquire genetic changes that allow them to grow uncontrollably and to move around the body. When a breast lump is found (by mammography or manual examination), a few cells are collected from the lump (a biopsy) to look for abnormal cells and to test for the presence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) on the cells. The hormones estrogen and progesterone promote the growth of normal breast cells and of ER+ and PR+ breast cancer cells. HER2 also controls the growth of breast cells. The receptor status of breast cancer is a major determinant of treatment options and prognosis (likely outcome). ER+ tumors, for example, are more receptive to hormonal therapy and have a better prognosis than ER− tumors, whereas HER2+ tumors, which make large amounts of HER2, are more aggressive than HER2− tumors. Breast cancer is treated by surgically removing the lump or the whole breast (mastectomy) if the tumor has already spread, before killing any remaining cancer cells with chemotherapy or radiotherapy. In addition, ER+, PR+, and HER2+ tumors are treated with drugs that block these receptors (including tamoxifen and trastuzumab), thereby slowing breast cancer growth.
Why Was This Study Done?
ER+ tumors predominate in white women but the proportion of ER+ tumors among US-born black women is slightly lower. The frequency of different receptor-defined subtypes of breast cancer in indigenous populations in Africa is currently unclear but policy makers need this information to help them decide whether routine receptor status testing should be introduced across Africa. Because receptor status is a major determination of treatment options and outcomes, it would be more important to introduce receptor testing if all subtypes are present in breast cancers in indigenous African women and if no one subtype dominates than if most breast cancers in these women are ER+. In this systematic review (a study that uses pre-defined criteria to identify all the research on a given topic) and meta-analysis (a statistical approach that combines the results of several studies), the researchers examine the distribution of receptor-defined breast cancer subtypes in indigenous populations in Africa.
What Did the Researchers Do and Find?
The researchers identified 54 relevant studies from North Africa involving 12,284 women with breast cancer (mainly living in Egypt or Tunisia) and 26 studies from sub-Saharan Africa involving 4,737 women with breast cancer (mainly living in Nigeria or South Africa) and used the data from these studies to calculate the proportions of ER+, PR+, and HER2+ tumors (the number of receptor-positive tumors divided by the number of tumors with known receptor status) across Africa. The proportion of ER+ tumors varied markedly between studies, ranging between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Among prospectively collected samples (samples collected specifically for receptor-status testing; studies that determined the receptor status of breast cancers using stored samples reported a lower proportion of ER+ disease than studies that used prospectively collected samples), the overall pooled proportions of ER+ and triple negative tumors were 0.59 and 0.21, respectively.
What Do These Findings Mean?
Although these findings highlight the scarcity of data on hormone receptor and HER2 status in breast cancers in indigenous African populations, they provide new information about the distribution of breast cancer subtypes in Africa. Specifically, these findings suggest that although slightly more than half of breast cancers in Africa are ER+, no single subtype dominates. They also suggest that the distribution of receptor-defined breast cancer subtypes in Africa is similar to that found in Western populations. The accuracy of these findings is likely to be affected by the low methodological quality of many of the studies and the lack of standardized procedures. Thus, large well-designed studies are still needed to accurately quantify the distribution of various breast cancer subtypes across Africa. In the meantime, the current findings support the introduction of routine receptor testing across Africa, especially for young women with early stage breast cancer in whom the potential to improve survival and reduce the years of life lost by knowing the receptor status of an individual's tumor is greatest.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Sulma i Mohammed
The US National Cancer Institute (NCI) provides comprehensive information about cancer (in English and Spanish), including detailed information for patients and professionals about breast cancer including an online booklet for patients
Cancer Research UK, a not-for profit organization, provides information about cancer; its detailed information about breast cancer includes sections on tests for hormone receptors and HER2 and on treatments that target hormone receptors and treatments that target HER2 is a not-for-profit organization that provides up-to-date information about breast cancer (in English and Spanish), including information on hormone receptor status and HER2 status
The UK National Health Service Choices website has information and personal stories about breast cancer; the not-for profit organization Healthtalkonline also provides personal stories about dealing with breast cancer
PMCID: PMC4159229  PMID: 25202974
19.  Isolated late metastasis from testicular seminoma presenting as a parotid gland mass: case report and review of the literature 
Current Oncology  2013;20(4):e354-e358.
Parotid metastases from non–head-and-neck cancers are rare and may represent a diagnostic and therapeutic challenge. A late metastasis to the parotid gland from a seminoma is an unusual manifestation of disease. A 45-year-old man with a history of testicular seminoma 5 years earlier presented with a rapidly progressing parotid mass. Ultrasonography and computed tomography showed a space-occupying lesion at the angle of the right jaw. The mass was infiltrating into the parotid gland and into the parapharyngeal space. A primary parotid neoplasm was suspected, and panendoscopy combined with open biopsy was performed. Histology examination confirmed a seminoma metastatic to the parotid gland, and comparison with the primary tumour showed identical histology. The patient received chemotherapy for recurrent seminoma in accordance with the pei (cisplatin, etoposide, ifosfamide) protocol. After 4 courses of chemotherapy, salvage radical parotidectomy with removal of all suspicious residual tumour tissue was performed.
This case illustrates the difficulties that may be encountered in the differential diagnosis of parotid gland masses and underlines the necessity for a detailed clinical history and for strong interdisciplinary collaboration between oncologists and pathologists to correctly diagnose cases with such unusual presentations.
PMCID: PMC3728065  PMID: 23904775
Seminoma; parotid gland; late metastasis
20.  Elective neck dissection in oral carcinoma: a critical review of the evidence 
More than 50% of patients with squamous cell carcinoma of the oral cavity have lymph node metastases and histological confirmation of metastatic disease is the most important prognostic factor. Among patients with a clinically negative neck, the incidence of occult metastases varies with the site, size and thickness of the primary tumour. The high incidence rate of occult cervical metastases (> 20%) in tumours of the lower part of the oral cavity is the main argument in favour of elective treatment of the neck. The usual treatment of patients with clinically palpable metastatic lymph nodes has been radical neck dissection. This classical surgical procedure involves not only resection of level I to V lymph nodes of the neck but also the tail of the parotid, submandibular gland, sternocleidomastoid muscle, internal jugular vein and spinal accessory nerve. It is a safe oncological surgical procedure that significantly reduces the risk of regional recurrences, however it produces significant post-operative morbidity, mainly shoulder dysfunction. Aiming to reduce morbidity, Ward and Roben described a modification of the procedure sparing the spinal accessory nerve to prevent post-operative shoulder morbidity. Several clinical and pathological studies have demonstrated that the pattern of metastatic lymph node metastases occurs in a predictable fashion in patients with oral and oropharyngeal carcinoma. The use of selective supraomohyoid neck dissection as the elective treatment of the neck, in oral cancer patients, is now well established. However, its role in the treatment of clinically positive neck patients is controversial. Some Authors advocate this type of selective neck dissection in patients with limited neck disease at the upper levels of the neck, without jeopardizing neck control. The main factors supporting this approach are the usually good prognosis in patients with single levels I or II metastasis independent of the extent of neck dissection, and the low rates of level V involvement in oral cavity tumours. Furthermore, the high incidence of clinically false-positive lymph nodes in oral cavity cancer patients is well recognized. In selected cases, supraomohyoid dissection could be extended to level IV, and followed by radiotherapy when indicated. Several reports have confirmed the usefulness of minimally invasive sentinel lymph node biopsy in melanoma and breast tumours. However, only preliminary data testing the feasibility of the method exist regarding the management of oral and oropharyngeal squamous cell carcinoma. The complexity of lymphatic drainage and the presence of deep lymphatics of the neck make application of this method difficult. This attractive concept has recently been explored by several investigators who examined the feasibility of identifying the sentinel lymph node in primary echelons of drainage from oral cavity squamous carcinoma. The current knowledge of sentinel lymph node biopsy does not allow avoiding the indication of elective neck dissection in clinical practice. Sentinel lymph node biopsy cannot be considered the standard of care at this time. However, there are multi-institutional clinical trials testing this approach. Management of occult neck node metastasis continues to be a matter of debate. The role of imaging methods such as ultrasound-guided needle biopsy, sentinel node biopsy and positron emission tomography-computed tomography are still being evaluated as alternatives to elective neck dissections. Whether one of these techniques will change the current management of cervical node metastasis remains to be proved in prospective multi-institutional trials.
PMCID: PMC2640044  PMID: 17883186
Oral cancer; Treatment; Neck dissection; Lymph nodes; Elective neck dissections
21.  Mycobacterium Tuberculosis Infection within a Warthin Tumor: A Case Report and Literature Review 
The co-existence of tuberculosis and a Warthin tumor in the parotid gland is extremely rare.
Case Report:
A 46-year-old male presented with a mass in the left parotid region of 6-month duration. The patient's history was only remarkable for a facial swelling, night sweats and a 38.5 C° fever. A 2 × 3-cm mobile, non-tender, mass with a smooth surface was palpated on left parotid tail. CT examination showed a well-defined 30 mm in diameter tumor mass in the left superficial lobe of the parotid gland. A superficial parotidectomy was performed. The final pathological diagnosis of the parotidectomy specimen was reported as a Warthin tumor and epitheloid granulomas with caseification necrosis. Purified protein derivative (PPD) was 30 mm in enduration. Two weeks after the antituberculosis treatment fever declined to normal values and night sweats decreased.
Tuberculosis can also be seen in parotid tumors which can coexist or mimic pleomorphic adenoma, Warthin tumor.
PMCID: PMC3842706  PMID: 24350077
Tuberculosis; Warthin tumor; Parotid gland
22.  Primary parotid tuberculosis mimicking parotid neoplasm: a case report 
Tuberculosis of the parotid gland is a rare clinical entity which causes some difficulties in diagnosis because of the similarities in presentation to that of a neoplasm. Diagnosis mainly relies in the treating physician having a high index of suspicion. The diagnosis is generally overlooked by otolaryngologists and most cases are undergoing unnecessary surgery.
Case presentation
A 20-year-old male presented with a mass in the right parotid region. The mass had been present for one year. Physical examination revealed a mobile, non-tender mass occupying the superficial lobe of the right parotid gland. Radiologic investigations revealed a well-defined, solid, mass lesion located in the posterior part of the superficial lobe of the right parotid gland. A provisional diagnosis of a neoplasm of the parotid gland was made and a right superficial parotidectomy was performed. Histopathologic examination of the specimen was reported as tuberculosis of the parotid gland. The patient was commenced on antitubercular chemotherapy.
Although rare, tuberculosis should be kept in mind and considered in the differential diagnosis of patients presenting with a solitary tumor in the parotid gland in order to avoid unnecessary surgery.
PMCID: PMC2267472  PMID: 18302769
23.  Salivary duct carcinoma of the parotid gland: A case report and review of the literature 
Oncology Letters  2014;9(1):371-374.
Salivary duct carcinoma (SDC) is a rare and aggressive parotid malignancy that most commonly affects males in the fifth and sixth decades of life. Histopathology specimens obtained from SDC patients demonstrate a resemblance to ductal carcinoma of the breast. Therefore, to distinguish SDC from breast ductal carcinoma, several immunohistochemical markers exist that may enable surgeons to make an accurate diagnosis. In this study, the case of a 54-year-old male with salivary duct carcinoma of the right parotid gland is presented. The results of the present case study revealed that the SDC sample was positive for the expression of human epidermal growth factor 2 (Her-2), cytokeratin (CK) 8/CK 18, p63, high molecular weight CK and calponin, and negative for expression of the estrogen receptor and progesterone receptor. Based on the result, an ipsilateral selective neck dissection followed by adjuvant post-operative radiation therapy was suitable at the primary treatment stage. At one year of follow-up, the patient was alive and free of recurrence. In advanced cases of SDC, treatment with anti-HER-2 monoclonal antibodies, such as trastuzumab, is recommended.
PMCID: PMC4246609  PMID: 25435994
salivary duct carcinoma; salivary gland; clinic; immunohistology
24.  Parotid gland-recovery after radiotherapy in the head and neck region - 36 months follow-up of a prospective clinical study 
The aim of the present study was to evaluate the recovery potential of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland.
Between 06/2002 and 10/2008, 117 patients with head and neck cancer were included in this prospective, non-randomised clinical study. All patients were treated with curative intent. Salivary gland function was assessed by measuring stimulated salivary flow at the beginning, during and at the end of radiotherapy as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were converted to flow rates and normalized relative to rates before treatment. Mean doses (Dmean) were calculated from dose-volume histograms based on computed tomographies of the parotid glands.
Patients were grouped according to the Dmean of the spared parotid gland having the lowest radiation exposure: Group I - Dmean < 26 Gy (n = 36), group II - Dmean 26-40 Gy (n = 45), and group III - Dmean > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By using IMRT as compared to 3D-CRT the Dmean of the spared parotid gland could be significantly reduced (Dmean IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The relative salivary flow rates (RFSR) as a function of the mean parotid dose after 24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in group III 31% and 24%, respectively. Multiple linear regression analyses revealed that the parotid gland dose and the tumor site were the independent determinants 12 and 36 months after the end of RT. Patients of group I and II parotid gland function did recover at 12, 24, and 36 months after the end of RT.
If a Dmean < 26 Gy for at least one parotid gland can be achieved then this is sufficient to reach complete recovery of pre-RT salivary flow rates. The radiation volume which depends on tumor site did significantly impact on the Dmean of the parotids, and thus on the saliva flow and recovery of parotid gland.
PMCID: PMC3201902  PMID: 21951317
head and neck cancer; irradiation; saliva; hyposalivation; parotid gland sparing; recovery
25.  A recurrent sialolipoma of the parotid gland: A case report 
Oncology Letters  2014;7(6):1981-1983.
Sialolipoma is a rare benign neoplasm and was recently described as a histological variant of intraoral lipoma. In the current report, the case of a of a 65-year-old female with a slow-growing mass in the right parotid gland with recurrence is presented. The initial clinical diagnosis was a benign salivary gland tumor. The tumor was situated between the right parotid gland and the right masseter muscle; therefore, a superficial parotidectomy was performed. Histopathology revealed that the tumor was a sialolipoma of the parotid gland. During the three-month follow-up, a recurrent right parotid tumor was identified in the deep lobe space of the right parotid gland and a deep lobe parotidectomy was performed. The present case demonstrates that although surgical excision is generally sufficient to treat parotid gland sialolipoma, postoperative follow-up is required as multifocal lesions may potentially remain, which could result in recurrence.
PMCID: PMC4049673  PMID: 24932274
recurrent sialolipoma; parotid gland; parotidectomy

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