Intraepithelial Extension Research Articles

Primary Gastrointestinal Malignant Melanoma

previously healthy, 51-year-old woman was Areferred to our hospital because of a gastric tumor adjoining the esophagogastric junction (EGJ). This tumor was discovered incidentally by an upper gastrointestinal (GI) series in the course of her annual medical check-up. The patient’s history was unremarkable. Physical examination and laboratory work-up showed no abnormalities. An esophagogastroduodenoscopy showed a dark-red EGJ tumor and a black blot accompanied by gray pigmentation scattered over almost the entire esophagus (Figure A and B). An endoscopic biopsy of the lesions showed proliferation of atypical melanocytes, which were immunohistochemically positive for the melanoma-specific antigen HMB-45 (Figure C). Further investigation showed no evidence for other manifestations of the malignant melanoma or metastasis from an extra-GI melanoma into these lesions. Preoperative computed tomography found no local or systemic metastases. The patient underwent a radical surgical resection with gastric tube pull-up. She received no adjuvant therapy although postoperative pathology showed lymph node metastasis in the upper mediastinum. She has been free of recurrence now for 1 year. Microscopically, the EGJ tumor presented some features of a skip lesion because it spread in the direction of the proximal esophageal epithelium and distal gastric mucosa (Figure D, red lines, skip lesions; yellow arrowhead, EGJ). This intraepithelial extension consisting of melanoma cells and atypical melanocytes is called radial growth (Figure E, green arrows), which is a definitive characteristic of primary mucosal melanoma (PMM). Although the exact tumorigenesis was unclear, these

Anorectal malignant melanoma with extensive intraepithelial extension: report of a case

Anorectal malignant melanoma (ARMM) is an extremely rare tumor with aggressive biological behavior. It is associated with a very poor prognosis and a 5-year survival rate of less than 10 %. There have therefore been a few reports of patients demonstrating long-term survival. We herein report a valuable case of long-term survival of a patient with ARMM with wide extension into the rectal mucosa, without endoscopic abnormalities.

Seminal vesicle intraepithelial involvement by prostate cancer: putative mechanism and clinicopathological significance.

We have recently shown seminal vesicle intraepithelial involvement of prostate cancer in cases with seminal vesicle invasion (pT3b). Based on the manner of seminal vesicle invasion, there could be 2 possible mechanisms of seminal vesicle intraepithelial involvement: direct intraepithelial invasion from prostate carcinoma in the muscular wall of seminal vesicles or intraepithelial involvement of cancer from the invaginated extraprostatic space (IES)/ejaculatory duct system to extraprostatic seminal vesicle. We aimed to clarify the manner and clinicopathological significance of seminal vesicle intraepithelial involvement. Of 1629 consecutive radical prostatectomies, 109 cases (6.7%) showed seminal vesicle invasion in whole-mounted radical prostatectomy specimens. In these pT3b cases, 18 (17%) showed seminal vesicle intraepithelial involvement by prostate cancer. Stromal invasion of the IES/ejaculatory duct system and ejaculatory duct intraepithelial invasion by prostate cancer were identified in 62 and 5 of 109 pT3b cases, respectively. However, the presence/absence of IES/ejaculatory duct system involvement by prostate cancer does not predict seminal vesicle intraepithelial involvement. No statistically significant correlation was observed between all pathologic parameters/biochemical recurrence and the presence/absence of seminal vesicle intra-epithelial involvement in the pT3b cases. These findings suggest that seminal vesicle intraepithelial involvement is more likely due to direct invasion of carcinoma from the muscular wall of seminal vesicles rather than intraepithelial extension from the ejaculatory duct system in the IES. Further studies with a substantially greater case number are needed to clarify the clinicopathological significance of seminal vesicle intraepithelial involvement in a better manner.

Involvement of Heparanase in the Pathogenesis of Localized Vulvodynia

Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 x 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.

Hepatectomy for Colorectal Liver Metastases with Macroscopic Intrabiliary Tumor Growth

We set out to clarify the clinicopathologic characteristics of colorectal liver metastases with macroscopic intrabiliary tumor growth and to determine optimal surgical management. Over 15 years, 6 of 103 patients undergoing hepatectomy for colorectal liver metastases had macroscopic intrabiliary tumor growth and were analyzed retrospectively. We performed 11 operations for the 6 patients, consisting of 10 hepatectomies (including 1 hepatopancreatoduodenectomy) and 1 pancreatoduodenectomy. Three patients survived more than 5 years: 1 died of pulmonary emphysema with no sign of recurrence 101 months after initial hepatectomy; the 2 others were alive with no sign of recurrence at 74 and 145 months after initial hepatectomy. Median survival time of all 6 patients was 87.5 months. Histologically, intrabiliary tumor growth had two components: intraluminal and intraepithelial extension. In the proximal direction, distance between these two components ranged from 4-10 mm. Aggressive surgical treatment can improve chances of long-term survival for patients with macroscopic intrabiliary growth of colorectal liver metastasis. Although nonanatomic limited resection is a common procedure for colorectal liver metastasis, anatomic hepatobiliary resection is recommended.

Proliferation of alpha-smooth muscle actin-containing stromal cells (myofibroblasts) in the lamina propria subjacent to intraepithelial carcinoma of the esophagus.

The lamina propria of the digestive tract is the space containing vessels, myofibroblasts, and other interstitial components. The present study was undertaken to elucidate the relationships between the proliferation of myofibroblasts within this space and other histological features such as inflammatory cell infiltration and proliferation of blood vessels. Thirty-eight cases in total-comprising 19 cases of early and 19 cases of advanced esophageal squamous cell carcinoma with intraepithelial extension (the former including 10 lesions of carcinoma in situ and 15 lesions of carcinoma with invasion only into the lamina propria)-were examined using H&E staining, Azan Mallory staining, and immunostaining for the characterization of mesenchymal cells in the lamina propria against alpha-smooth muscle actin (alphaSMA), desmin, vimentin, factor VIII, collagen type IV, laminin, or inflammatory cells (L26, UCHL1, Kp1, and c-kit). The proliferative potential of myofibroblasts was evaluated by measuring the total length of the bundles of myofibroblasts per case. Proliferation of alphaSMA-containing stromal cells: i) occurred in the lamina propria subjacent either to intraepithelial carcinomas (64%) or to the intraepithelial extension of carcinoma tissue (47%), and ii) showed a significant correlation with both the degree of mononuclear cell infiltration (mostly UCHL1-positive T cells) and the total length of the carcinoma tissue in each case. Proliferation of alphaSMA-containing stromal cells in the lamina propria may be involved in altering the endoscopic features of the esophagus in cases with intraepithelial carcinoma or an intraepithelial extension of carcinoma tissue.

Clonal analysis of high-grade squamous intra-epithelial lesions of the uterine cervix.

We previously reported that invasive squamous cell carcinomas of the uterine cervix are of monoclonal composition. In the current study, we extended our previous work to determine the clonal composition of cases of high-grade squamous intra-epithelial lesion (HSIL). Clonal analysis targeting the HUMARA locus was performed on cervical tissue from 9 cases, 8 showing heterozygosity at the HUMARA locus and being, therefore, informative for clonality analysis. Uterine cervices were cut into 12 blocks, fixed with formalin and embedded in paraffin, and DNA was extracted from targeted lesions of each block. A total of 30 samples of cervical intra-epithelial neoplasia 3 (CIN3) (14 samples of carcinoma in situ and 16 samples of severe dysplasia) and 1 sample of CIN2 (moderate dysplasia) were analyzed. Monoclonal composition of the lesions was demonstrated in 30/30 cases of CIN3. Polyclonal composition was seen in the single case of CIN2. In 6 uterine cervices, in which dysplastic lesions were present in more than 3 blocks, the pattern of X-chromosome inactivation was the same in all lesions, suggesting that these individual lesions were derived from a single cell, with intraepithelial extension within the cervical mucosa. By contrast, one uterus contained 2 discontinuous dysplastic foci with different patterns of X-chromosome inactivation, indicating that the 2 lesions developed independently from each other. Our results demonstrate that (i) lesions of CIN3 (severe dysplasia and carcinoma in situ) are composed of a clonal neoplastic population of cells and (ii) most cases of HSIL are unifocal in origin.

Lugol staining pattern and histology of esophageal lesions.

To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II, normal greenish brown staining; grade III, less intense staining; and grade IV, unstained. Most of the grade IV lesions were invasive carcinomas, carcinomas in situ, or severe dysplasia. The carcinomas in situ and the intraepithelial extension of the carcinomas, which were difficult to detect, were clearly shown as grade IV. On the other hand, moderate to mild dysplasia or atrophy showed grade III staining. Grade IV lesions showed well-demarcated sharp margins, whereas grade III lesions showed ill-demarcated dull margins. The grade III carcinomas, however, by the Lugol test, showed well-demarcated margins. Histologic evaluation disclosed that the staining intensity reflected well the thickness of the glycogen-containing cell layer in the lesion. The sharpness of the margin reflected the abrupt or gradual change from the glycogen-containing to non-containing cell layers. These findings suggest 1) the usefulness of the staining pattern of the Lugol test for the diagnosis of esophageal lesions such as squamous cell carcinoma and severe dysplasia, and 2) the usefulness of the Lugol test for precise delineation of the proximal resection line during surgery of esophageal carcinomas with unexpected wide extension.

Roentgenographically occult bronchogenic carcinoma of non-polypoid type: histological patterns of longitudinal growth within the bronchus.

Microscopy of the serial block-sections of the entire bronchial tree of all the resected specimens of roentgenographically occult bronchogenic carcinoma revealed new findings with respect to the histological patterns of longitudinal growth within the bronchial wall. Twenty-seven lesions which were non-polypoid on gross appearance with longitudinal extension of 16 mm and above were classified into the following four categories. (A) In standard superficial extension, transmural invasion by carcinoma became shallower and the area involved on section became smaller gradually from the site of the origin of carcinoma to the proximal and distal ends. (B) In intraepithelial extension, carcinoma was confined within the epithelium throughout the bronchi involved except at and near the site of the origin at which it penetrated the basement membrane. (C) In lymphatic extension, carcinoma extended from the site of the origin to the proximal and distal ends in a dual pattern so that it extended longitudinally within the epithelium in parallel with an invasion into the lymphatic vessels in the lamina propria and submucosa. At the site of the origin carcinoma invaded down to the level of the submucosa or adventitia. (D) In massive extension, a massive invasion by carcinoma from the site of the origin to the proximal and distal ends, and a simultaneous invasion and destruction by carcinoma of the epithelium, basement membrane, lamina propria, submucosa, and of adventitia in places were demonstrated. There was no marked difference in bronchoscopic finding among (A), (B) and (C). The length of the lesion as estimated by histology was different from that observed at bronchoscopy. Bronchoscopic examination was not always successful in determining the line of resection precisely. Therefore it is indispensable to examine frozen sections and/or imprint specimens of the margin of resection.

Corneal Sensitivity after Epikeratophakia

Corneal sensitivity was tested in 60 eyes of 30 patients who underwent unilateral epikeratophakia for the correction of aphakia (20 patients) or keratoconus (10 patients). Postoperative recovery time ranged from 2 months to 21 months (mean: 10 months). Our results indicate a relative hypesthesia of the epikeratophakia lenticule when compared with the peripheral host cornea and contralateral control cornea. However, corneal sensitivity tested in 11 patients with more than 1 year follow-up was increased compared with the sensitivity of 19 patients whose postoperative recovery was less than 1 year. Histopathologic findings in two lenticules from a nonhuman primate demonstrated sparse epithelial axon terminals. Host corneal nerves appear to innervate the lenticules by intraepithelial extension and by penetration of the superficial keratectomy scar.

AN UNUSUAL CASE OF EXTRAMAMMARY PAGET'S DISEASE

A patient, having been treated by total cystectomy and Bricker's conduit operation for prostatic duct carcinoma with intraepithelial extension into the prostatic urethra and bladder, developed an annular, psoriasiform eruption around the external orifice of the urethra two and one-half years later. A biopsy of this lesion showed pagetoid changes of the epidermis. Microscopic examination of the surgical specimen, consisting of the glans penis and corpus spongiosum, demonstrated intraepithelial-tumor permeation into the glans penis, penile urethra, and periurethral glands (Littre). It seems reasonable to conclude that this is an unusual case of Paget's disease of the glans penis which probably originated from a prostatic duct carcinoma.

In situ carcinoma of the prostate with intraepithelial extension into the urethra and bladder.

In situ carcinoma of the prostate with intraepithelial extension into the urethra and bladder.