ZIP14 zinc transporter downregulation and zinc depletion in the development and progression of hepatocellular cancer.

PURPOSE: Hepatocellular cancer (HCC) is a deadly and most rapidly increasing cancer in the USA and worldwide. The etiology and factors involved in development of HCC remain largely unknown. A marked decrease in zinc occurs in HCC. Its role and involvement in HCC has not been identified. We investigated the relationship of cellular zinc changes to the development of malignancy, and the identification of potential zinc transporters associated with the inability of hepatoma cells to accumulate zinc. METHODS: The detection of relative zinc levels in situ in normal hepatic cells vs. hepatoma was performed on normal and HCC tissue sections. ZIP1, 2, 3, and 14 transporters were identified by immunohistochemistry. RESULTS: Intracellular zinc levels are markedly decreased in HCC hepatoma cells vs. normal hepatic cells in early stage and advanced stage malignancy. ZIP14 transporter is localized at the plasma membrane in normal hepatocytes, demonstrating its functioning for uptake and accumulation of zinc. The transporter is absent in the hepatoma cells and its gene expression is downregulated. The change in ZIP14 is concurrent with the decrease in zinc. ZIP1, 2, 3 are not associated with normal hepatocyte uptake of zinc, and HCC zinc depletion. HepG2 cells exhibit ZIP14 transporter. Zinc treatment inhibits their growth. CONCLUSIONS: ZIP14 downregulation is likely involved in the depletion of zinc in the hepatoma cells in HCC. These events occur early in the development of malignancy possibly to protect the malignant cells from tumor suppressor effects of zinc. This provides new insight into important factors associated with HCC carcinogenesis.

Sialolipoma of the lower lip: case report and literature review.

Sialolipoma is a relatively rare and fairly recently described as a variant of lipoma with salivary elements. Any site within the oral and maxillofacial region may be involved with the parotid gland being the most common location. Herein, we present a case of silaolipoma in lower lip. The clinical and histological features and differential diagnosis are discussed.

Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is an untreatable deadly cancer. The factors involved in its early development remain unknown; which contributes to the absence of biomarkers for early detection of malignancy or at-risk subjects, and the absence of efficacious therapeutic agents. Because zinc changes are implicated in some cancers, we determined if it might be involved in the development of pancreatic adenocarcinoma. With in situ Dithizone and Zinquin staining of normal pancreas and adenocarcinoma tissue sections, we show for the first time, a consistent major loss of zinc in ductal and acinar epithelium in adenocarcinoma compared to the normal epithelium. This decrease in zinc is evident in well-differentiated through poorly-differentiated stages of malignancy. Immunohistochemistry identified ZIP3 as the basilar membrane zinc uptake transporter in normal ductal/acinar epithelium; and that the transporter is absent in adenocarcinoma. In situ Rt-PCR revealed that ZIP3 gene expression is silenced in adenocarcinoma. The ZIP3 down regulation accompanied the loss of zinc in early and progressing malignancy. RREB1 transcription factor was down regulated along with ZIP3; and might be involved in the silencing of ZIP3 expression. Zinc treatment was cytotoxic to malignant Panc1 cells. The combination of concurrent zinc, ZIP3, and RREB-1 changes represent early events in the development of adenocarcinoma; and suggest that zinc might be a tumor suppressor of pancreatic cancer. This report provides the clinical foundation for further mechanistic studies that will provide important insight into pancreatic carcinogenesis, and can lead to the development of effective early biomarkers and effective therapeutic agents for pancreatic cancer.

Follicular lymphoid hyperplasia of the palate: case report and literature review.

Follicular lymphoid hyperplasia (FLH) of the palate is a very rare benign, proliferative process, with only 20 cases published so far in the English language literature. We describe a case, in a 55-year-old Caucasian female, who developed a swelling in the left posterior hard palate. Bony involvement was absent. Importantly, the medical history was positive for a previous non-Hodgkin lymphoma. Following incisional biopsy, histological examination revealed a vaguely nodular lymphoid proliferation composed of small well-differentiated lymphocytes. The lymphoid follicles were positive for CD20, CD79a, CD10, CD21 and BCL6, while negative for BCL2. The parafollicular areas revealed positivity for CD3, CD5, CD30, and CD15. Both areas were CD45 positive. Subsequent immunoglobulin heavy chain gene rearrangement analysis revealed a polyclonal lesion. No further treatment was instituted, and the patient is currently being followed-up every three months. This report demonstrates that FLHs are especially important due to their clinical and, occasionally, microscopic resemblance to follicular lymphomas. Morphologic and immunohistochemical analyses and molecular studies are essential to achieve accurate diagnosis and to implement appropriate management.

Granulomatous foreign-body reaction involving oral and perioral tissues after injection of biomaterials: a series of 7 cases and review of the literature.

PURPOSE: Injectable implants used for soft-tissue augmentation may lead to a granulomatous foreign-body reaction. The aim of this report is to present 7 new cases of foreign-body granulomas involving the oral and perioral tissues, after injection of biomaterials to achieve soft-tissue augmentation. In addition, the clinical and epidemiological profile of this condition is summarized, based on a review of the English-language literature of all previously described cases. PATIENTS AND METHODS: We report on 7 new cases of granulomatous foreign-body reaction involving the oral and perioral tissues after the injection of biomaterials. A comprehensive literature review is also presented. RESULTS: The literature search revealed 49 cases of this condition affecting the oral and perioral tissues. Our 7 patients were female, with a mean age of 52.8 years (range, 34 to 70 years). The lower lip was affected in 4 cases, 1 case was located in the upper lip, 1 case in the buccal mucosa, while 1 case involved 2 different sites (upper lip and buccal mucosa). Histopathologic examination revealed numerous cells with clear, often multiple, cytoplasmic vacuoles, bearing a resemblance to lipoblasts. Immunohistochemistry revealed diffuse positivity for the histiocytic marker CD68. CONCLUSIONS: The diagnosis of granulomatous foreign-body reactions may be challenging because of their microscopic resemblance to liposarcoma, and because of the occasional reluctance of patients to report the previously performed esthetic procedure. A clinical history, histopathologic examination, and immunohistochemical analysis (as needed) are essential in achieving an accurate diagnosis.

Angioleiomyoma of the tongue.

A case of angioleiomyoma of the tongue is detailed. The patient sought treatment for a painless, rubbery mass of 10 years duration. The tumor was unusual, appearing bilobed, with the dorsal aspect whitish in color and a blue ventral component. Occasional episodes of numbness were noted. Biopsy of the lesion demonstrated bundles of smooth muscle cells surrounding numerous vascular spaces. The patient was lost to follow-up; as a result, a complete surgical excision of the tumor was not performed.

Clinicopathologic characterization of oral angioleiomyomas.

OBJECTIVE: The purpose of this study was to better define the clinicopathologic features of oral angioleiomyomas. STUDY DESIGN: A retrospective search was performed for angioleiomyomas among all smooth muscle tumors accessioned from 1963 to 2001 in an oral pathology service. Twelve lesions met histopathologic criteria for inclusion in the study and were combined with 97 additional cases identified from the English language literature, yielding 109 cases for evaluation. RESULTS: The mean age of the patients with oral angioleiomyomas was 45.0 years, with a 1.43:1 male to female predilection. The most frequently reported site was the lip, in 48.6% of patients, followed by the palate (21.1%), buccal mucosa and tongue (each 9.2%), mandible (8.3%), and buccal sulcus, labial sulcus, floor of mouth, and gingiva (each 0.9%). Most mucosal lesions varied in size from a few millimeters to 2 cm, with most central lesions of the mandible measuring greater than 2 cm. Although angioleiomyomas are vascular lesions, only 55.9% of cases appeared red, blue, or purple; the remainder were gray, white, or the color of normal mucosa. Tumors were typically described as painless and manifested a low growth rate. All lesions were well circumscribed and composed of numerous vascular spaces surrounded by thick smooth muscle walls. CONCLUSION: Oral angioleiomyomas are benign smooth muscle tumors with a limited degree of morbidity. Careful histologic inspection is necessary to distinguish these lesions from their malignant counterpart, the leiomyosarcoma. Surgical excision is the treatment of choice, and recurrence is rarely encountered.