The spindle cell and mucoepidermoid variants tend to be more aggressive and have an increased risk of recurrence. CIN, by definition, has an intact basement membrane.
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SCCA , on the other hand, invades through the basement membrane and into adjacent tissues, in which case tumor cells are seen in the conjunctival stroma. Surgical excision alone has been associated with a higher rate of recurrence compared to excision with adjunctive cryotherapy. Surgical treatment includes complete local excision of the lesion, with at least 3—4 mm margins.
Three distinct portions of a typical CIN lesion must be addressed surgically: corneal, limbal, and conjunctival. Occasionally the conjunctival component also has a deeper extension that must be approached in a specific surgical manner. Scraping is carried out from approximately 1—2 mm into normal cornea, scraping toward the limbus.
The limbal component is excised with 3—4 mm circumferential margins. If the extent of the CIN is so large that these margins would compromise the amount of residual limbal stem cells, smaller margins can be taken.
At least a few clock hours of normal limbal stem cells must remain in order to re-epithelialize the cornea. The involved limbus can be scraped with a No. The slow thaw is thought to cause rupture of cell membranes leading to cell death and potentially killing microscopic disease. The conjunctival portion is excised with 3—4 mm margins.
Care must be taken when dissecting in the area of the rectus muscles. Wet-field cautery is used for hemostasis. The tissue specimen to be sent to pathology for evaluation should be oriented on a piece of filter paper and allowed to dry in place for 30—60 seconds, and the paper should be labeled in pencil prior to placement in formalin. Adjunctive cryotherapy, in a double freeze-slow-thaw technique, is regularly applied to the affected limbus and conjunctival margins in an attempt to eliminate microscopic tumor burden. Cautery may also be helpful in this regard. One need not routinely treat the scleral bed underlying freely mobile conjunctival tumors.
If only minimal fixation is noted, cryotherapy to the involved scleral bed is appropriate. If, however, possible deeper involvement is evident or the tumor is fixated to the episclera or sclera, a more aggressive surgical approach is indicated. The degree of surgical aggressiveness is a matter of clinical judgment. The physician may wish to wait for pathologic confirmation of invasion prior to empiric scleral resection. With obvious tumor involvement, a thin lamellar scleral dissection is performed by outlining the affected sclera with a No.
The No. In cases of severe scleral bed involvement, cryotherapy to the affected area may follow the lamellar dissection. If extensive tissue is removed, an amniotic membrane, scleral, or corneal graft can be sutured into place over the bare sclera and cornea. In smaller lesions, the conjunctival margins can be left to heal by secondary intention. If the patient develops limbal stem cell deficiency and problems with epithelialization, a limbal stem cell transplant can be performed once tumor resolution is complete.
This report included varied surgical approaches, from excision alone, to excision with adjunctive radiation or cryotherapy. The time to recurrence after the first excision ranged from 33 days to The average was 3. Risk factors for recurrence include positive margins and possibly cell type mucoepidermoid and spindle cell on pathologic evaluation.
In cases of recurrent tumor or large, annular, limbal lesions, extensive surgical manipulation may lead to compromise of the ocular surface. Specifically, removal of too much tissue may lead to limbal stem cell deficiency and cicatricial changes. Therefore other treatment options have been used. Table 1 describes the formulation of these chemotherapeutic agents. Radiation is complicated by retinopathy, corneal epitheliopathy, and cataract formation, and has fallen out of favor. The concentrations range from 0. Most studies have concluded that use for longer than 14 days can lead to severe irritative symptoms pain, photophobia, blepharospasm.
The use of topical MMC can also be complicated by hyperemia, allergy, corneal epithelialopathy, and possibly scleral melting. For that reason, most clinicians treat in cycles of up to 14 days, with a 1—2-week rest period between cycles. As many as four cycles can be necessary to affect a cure.
Some ocular surface side effects can be successfully treated with the administration of topical steroid drops three to four times per day in the rest period while MMC is discontinued. The use of punctal plugs during treatment with MMC prevents punctal stenosis and absorption into the nasal mucosa. MMC requires refrigeration and must be discarded after 2 weeks.
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If tolerated by the patient, the day treatment regimen maximizes the shelf life and cost of MMC. Different treatment regimens have been described. Seven of eight patients demonstrated complete regression, while one patient was cured after a second 4-week retreatment.
Using this regimen, four out of seven patients were cured, two of the remaining patients improved with re-treatment, while one patient required MMC treatment to achieve resolution. Like MMC, 5-FU may lead to ocular surface irritation, corneal defects, and skin discomfort, but the 2—4 days-per-month dosing is well tolerated. The exact mechanism of action, however, is not yet known.
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It has also been used successfully in the treatment of cervical intraepithelial neoplasia and squamous lesions of the skin which, like SCCA, have been associated with HPV. One treatment regimen includes the injection of 0.
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Tumor resolution seems to require dosing correlated with the size of the lesion, and injections may need to be repeated every week up to three times a week until clinical resolution is observed. The physician may find that topical administration of interferon IFN is effective but produces a slower resolution compared with injections of IFN. The initial protocol for patients who are not surgical candidates, who develop recurrence, or have annular lesions, includes the use of a topical chemotherapeutic agent.
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Topical IFN is gentle and easily tolerated by the patient. It is, however, slower than MMC. The response rate to resolution is quicker with injections, but patients tend to prefer drops. The tumor response with injection appears to be dose-dependent. Patients who prefer not to have periocular injections may be treated topically. Patients need to be advised that topical treatment with IFN may take 3 months or more.
If the tumor responds, this treatment may be continued and tapered slowly as described above. Recurrence may be related to incomplete surgical excision. Achieving negative margins at the time of primary resection is the goal. If the tumor does not seem to be responding to the initial chemotherapeutic choice, a different agent may be tried. Patient factors may determine which of these chemotherapeutic agents are used first, including informed consent, side-effect profiles, and cost.
The risk factors for malignant melanoma include ultraviolet radiation exposure and genetic factors, including xeroderma pigmentosa. Clinically, the most important risk factors are conjunctival nevi and primary acquired melanosis PAM. The clinical features of pigmented conjunctival lesions are described below and compared in Table 2. A conjunctival nevus usually appears during the first or second decade of life, most commonly in the interpalpebral zone.
On examination, a nevus is pigmented, discrete, slightly elevated, and tends to contain cysts. Researchers think PIA begins after an infection, toxin, or some other factor causes epithelial tissue in the prostate to atrophy or become inflamed. Cells in the affected area begin to proliferate faster than normal. It is also not clear at this time if PIA leads to PIN, or if it represents an alternative pathway in the progression to cancer.
The condition is usually diagnosed either during a prostate biopsy or when prostate tissue is removed during transurethral resection of the prostate TURP , a treatment for benign prostatic hyperplasia. The classification matters, because low-grade PIN does not increase your risk of developing prostate cancer, while high-grade PIN might. Partly for that reason, it is unclear how many men can expect to be diagnosed with high-grade PIN in any given year.
There may be racial differences in the likelihood of developing high-grade PIN, although it is not known why — and few studies have examined the issue. An analysis of autopsies conducted in Brazilian men, some white and some of African descent, reported similar findings.
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