Stromal Degeneration Research Articles

Histopathology-based diagnosis of Mooren’s ulcer concealed beneath the pterygium on eye

ABSTRACT Mooren’s ulcer (MU) is a chronic and painful ulcerative keratitis that is difficult to diagnose, especially when concealed beneath the pterygium, which is a common, benign, wedge-shaped, fleshy tissue growth of the conjunctiva extending onto the cornea. The coexistence of MU and pterygium is extremely rare. A 41-year-old man presented with a 2-month history of unprovoked redness, pain, and blurred vision in the right eye. Corneal epithelial defects around the pterygium head were noted upon slit-lamp examination and fluorescein staining. The patient was initially misdiagnosed with a corneal epithelial defect and pterygium. The initial treatments with anti-inflammatory and corneal epithelial growth promotion tear agents failed. Anterior segment optical coherence tomography (AS-OCT) showed corneal stromal lysis thinning, and in vivo confocal microscopy (IVCM) revealed marked inflammatory cell infiltration and stromal degeneration. We suspected the pathology was an immune-related or tumor-related corneal ulcer. The MU concealed beneath the pterygium was diagnosed by histopathological examination of a biopsy specimen that presented typical localized loss of the corneal epithelium and Bowman’s layer, stromal degeneration, and inflammatory cell infiltration. Finally, we performed lamellar keratoplasty (LKP) combined with pterygium excision surgery. The patient recovered with no complications or recurrence during the 1-year follow-up period. Few cases of MU concealed beneath the pterygium have been reported. It is beneficial to rule out the pathological changes concealed beneath the pterygium, combined with multiple means of examination such as slit-lamp examination, AS-OCT, and IVCM. A histopathological examination should be performed to establish a diagnosis.

Vitamin D improves oxidative stress and histopathological damage in rat ovaries caused by hyperthyroidism.

The aim of this study is to investigate the histopathological and biochemical efficacy of vitamin D on oxidative damage and fibrosis in rat ovaries induced by experimental hyperthyroidism. This study is a comparative, prospective experimental rat study. Sprague-Dawley female rats were divided into four groups. Only distilled water was given to the rats in group 1 for 25 days. In group 2, 100 μg/day L-thyroxine was given to rats for 25 days. In Group 3, 100 μg/day L-thyroxine and 200 IU/day vitamin D were given to rats for 25 days. In group 4, only 200 IU/day vitamin D was administered for 25 days. This study is the first to demonstrate the protective effect of vitamin D against ovarian damage caused by experimental hyperthyroidism. Hyperthyroidism caused fibrotic degenerative changes in the ovaries and an increase in the fibrillin 1 score. It caused serum follicle-stimulating hormone (FSH) levels to increase and serum E2 levels to decrease. In addition, malondialdehyde (MDA) and total oxidant status (TOS) levels increased in rats with hyperthyroidism. Vitamin D decreased MDA and TOS values and increased total antioxidant status (TAS) values in rats with hyperthyroidism. It also increased TSH values by causing a decrease in TT3 and TT4 values. It decreased fibrosis, follicle degeneration, stromal degeneration, and fibrillin 1 score in ovarian tissue. Vitamin D has positive histopathological and biochemical effects on the oxidative stress and follicle damage caused by hyperthyroidism in ovarian tissue. Human studies with larger case populations should be conducted to evaluate the effects and clinical applications of vitamin D.

Clinicopathological study of recipients’ corneal tissue excised during penetrating keratoplasty. Best out of waste!

Introduction: Corneal buttons removed during penetrating keratoplasties (PK) from recipients’ which were routinely discarded were studied with aim to analyze the common indications of PK and changing pattern of corneal diseases in developing countries like India. Materials and Methods: This is an observational case series carried out in tertiary care hospital of central India from October 2012 to October 2014. Histopathology of 156 corneal tissues was done of which 75 were recipients’ corneal tissues removed during PK and 81 were residual adjacent donors’ corneal tissues left out after corneal button was removed for transplant. Results: The most common indication of PK in our study was corneal ulcer (n=37, 49.33%), followed by infectious keratitis (n=22, 29.33%) which included ulcers in various stages of healing and complications associated with ulcer like adherent leucoma. Amongst infectious keratitis, 17 were (77.27%) of bacterial keratitis and 5 (22.73%) of fungal keratitis. Followed by bullous keratopathy 8(10.66%), 3(4%) of graft rejection and one each (1.33%) of Fuchs’ dystrophy and chronic actinic keratopathy. Of 81 donor’s corneal tissues, 75 were the residual corneal tissues from corneo-conjunctival junction which were transplanted within stipulated time. Only one case showed changes of chronic actinic keratopathy, rest showed normal histology. 6 corneas which were not transplanted within stipulated time showed epithelial denudation and stromal degeneration with loss of keratocytes. Conclusion: Histopathology gives additional insight to clinical diagnosis. Specific diagnosis can be commented in corneal opacities and infectious keratitis. Keywords: Penetrating Keratoplasty, PK, Histopathology, Corneal buttons, Recipient.

Surgical management of infectious and noninfectious melting corneal ulcers in cats

A melting ulcer, characterized by the stromal dissolution of the cornea, is an important eye lesion that develops due to various reasons and threatens vision. Restoration of this lesion, which causes loss of corneal transparency, requires aggressive medical and surgical treatment. In medical treatment, stromal degeneration is controlled with agents that support topical antibacterial and stromal healing. Surgical treatment is applied using various techniques to remove structures damaged due to the progression of corneal melting and to promote corneal healing. In this study, lamellar keratectomy and the third eyelid flap techniques were combined with topical medical therapy in 20 cat cases with melting ulcers. The aim of this study was to alert to general practitioners that this condition is an important cause of progressive eye loss and necessitates urgent intervention and to show that this treatment approach is easy to implement and has successful results. Key words:

Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage.

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Twenty-one Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were allocated to 3 groups (n = 7/group): control, single dose of vehicle (Dimethyl Sulfoxide [DMSO]); DOR, single reduced chemotherapy dose; and POI, single standard chemotherapy dose. After 21 days, mice underwent ovarian hyperstimulation and mating. Part of the animals were harvested to analyze ovarian reserve, ovulation and fertilization rates, and morphology, apoptosis, and vascularization of the ovarian stroma. The remaining mice underwent multiple matings to assess pregnancy rates and litter sizes. The DOR and POI mice showed an impaired estrous cyclicity and a decrease in ovarian mass, number of follicles, Metaphase II (MII) oocytes, and embryos as well as in ovarian stroma vascularization. Mice in both models showed also an increase in the percentage of morphologically abnormal follicles, stromal degeneration, and apoptosis. Similar to that observed in DOR and POI patients, these impairments were less severe in DOR than in POI mice. None of the POI females were able to achieve a pregnancy. Meanwhile, DOR females achieved several consecutive pregnancies, although litter size was decreased when compared to controls. In conclusion, a mouse model which displayed most of the ovarian characteristics and fertility outcomes of women with DOR has been established using a single dose of chemotherapy.

Remission of Spontaneous Canine Tumors after Systemic Cellular Viroimmunotherapy.

Dogs with spontaneous tumors treated in veterinary hospitals offer an excellent opportunity for studying immunotherapies, including oncolytic viruses. Oncolytic viruses have advanced into the clinic as an intratumorally administered therapeutic; however, intravenous delivery has been hindered by neutralization in the blood. To circumvent this hurdle, mesenchymal stem cells have been used as a "Trojan horse." Here, we present the treatment of 27 canine patients with cancer with canine mesenchymal stem cells infected with ICOCAV17, a canine oncolytic adenovirus. No significant adverse effects were found. The response rate was 74%, with 14.8% showing complete responses, including total remissions of lung metastasis. We detected virus infection, stromal degeneration, and immune cell infiltration in tumor biopsies after 4 weeks of treatment. The increased presence of antiadenoviral antibodies in the peripheral blood of treated dogs did not appear to prevent the clinical benefit of this therapy. These data indicate that oncolytic viruses loaded in mesenchymal stem cells represent an effective cancer immunotherapy.Significance: The classical clinical limitations of antitumoral viroimmunotherapy can be overcome by use of mesenchymal stem cells.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4891/F1.large.jpg Cancer Res; 78(17); 4891-901. ©2018 AACR.

Endocytosis of keratinocytes in oral squamous cell carcinoma

Objectives: To quantify endocytosis of keratinocytes (EK) in oral squamous cell carcinoma (OSCC) and correlate it with different clinical and histopathological parameters. Further, the expression of cluster of differentiation 68 (CD68) and lysozyme was studied in tumor cells to corroborate this phenomenon. Materials and method: EK per high-power field (HPF) was calculated on hematoxylin and eosin-stained sections and correlated with clinical and histopathological parameters. CD68 and lysozyme were studied in tumor cells using immunohistochemistry. Results: The mean EK per HPF was higher in stage IV (4.450 ± 2.241) than stage III (3.333 ± 1.543) OSCC ( p = 0.1978). Although there were more EK in N2 stage (4.362 ± 0.3405) as compared to N0–N1 (3.462 ± 0.4178), the results were statistically insignificant. Statistically significant difference in mean EK was observed in all the grades of OSCC: well versus moderate ( p = 0.0052), moderate versus poor ( p < 0.0001), and well versus poor ( p = 0.0001). There were significant differences in the mean EK ( p < 0.05) between different grades of stromal degenerations (mild: 2.654 ± 1.093, moderate: 5.115 ± 1.774, and severe: 7.250 ± 2.217). Statistically significant differences were observed in CD68 expression in tumor cells of various TNM stages ( p = 0.049), histopathological grades ( p = 0.045), and stromal degeneration ( p = 0.024). Likewise, lysozyme expression in tumor cells was also statistically significant in histopathological grades ( p = 0.004) and mean EK value ( p = 0.0119). Conclusion: The mean EK in OSCC increases with increasing histopathological grades, TNM stages, and stromal degeneration. CD68 and lysozyme can be used as markers of EK in OSCC.

Therapeutic effect of sunitinib on diabetes mellitus related ovarian injury: an experimental rat model study

The aim of our study is to investigate the effect of sunitinib on diabetes mellitus related-ovarian injury and fibrosis in rat models. An experimental diabetes mellitus model was created in 16 rats, and eight rats with normal blood glucose levels were included in control group (Group-1). The diabetic rats were divided into two groups:diabetic control group (water given) – Group-2 and sunitinib treatment group – Group-3. After four weeks, bilateral oophorectomy was performed and ovaries were examined histologically. The groups were compared by Student’s t-test, analysis of variance (ANOVA) and Mann–Whitney’s U-test. There was a significant increase in no-medication (water given) diabetic rat’s ovary (Group-2) in terms of follicular degeneration, stromal degeneration, stromal fibrosis and NF-kappaB immune-expression compared with control group normal rats’ ovary (Group-1) (p < 0.0001). Stromal degeneration (p = 0.04), stromal fibrosis (p = 0.01), follicular degeneration (p = 0.02), NF-kappaB immune-expression (p = 0.001) significantly decreased in sunitinib-treated diabetic rat’s ovary (Group-3) when compared with no-medication (water given) diabetic rat’s ovary (Group-2) (p < 0.05). When we used sunitinib in the treatment of diabetic rats, ovarian injury, fibrosis and NF-kappaB immunoexpression decreased significantly. The effects of sunitinib in rat models give hope to the improved treatment of premature ovarian failure due to diabetes mellitus in humans.

Warthin's tumor: an unknown pathogenesis: a neoplasm or a reactive hyperplasia?

To examine the probable role of angiogenesis and lymphangiogenesis in the pathogenesis of Warthin's tumor. Sixty-one patients with Warthin's tumor (n = 40), branchial cysts (n = 6), thymic cysts (n = 3), or tonsillar lymphoepithelial cysts (n = 12) were included. Forty Warthin's tumors were used as the lesion group, and 21 lymphoepithelial cysts were used as a control group. 29 lymph nodes around the Warthin's tumor, four of which showed salivary duct inclusions, were also evaluated. Blood vessel density was defined as an indicator of angiogenesis by examining CD31 and FVIII Ag expression, and lymphatic vascular density was defined as an indicator of lymphangiogenesis by evaluating LYVE-1 and podoplanin expression by immunohistochemical analysis. Data are expressed with descriptive statistics. Comparative analysis was performed using Shapiro-Wilks, Mann-Whitney U, and Kruskal-Wallis tests. A P < 0.005 was considered to indicate statistical significance. Statistical analysis was performed using the MedCalc ® v.10.3.0 software. The lesion group had higher mean values of age (58 vs. 11 years, P = 0.001), smoking rate (92.3% vs. 19%, P < 0.001), stromal degeneration (100% vs. 42.9%, P < 0.001), lymph node involvement around the lesion (87.9% vs. 12.1%, P < 0.001), salivary duct inclusion (25% vs. 0%, P = 0.0001), than those of lymphoepithelial cysts. Blood vessel density (51.92 ± 25.64 vs. 8 ± 5.35, number/5 high power fields (HPF), P < 0.001) and lymphatic vascular density (68.95 ± 21.32 vs. 21.10 ± 4.05 number/5 HPF, P < 0.001) were higher in Warthin's tumors than lymphoepithelial cysts. Warthin's tumors, and lymph nodes with inclusions had similar levels of blood and lymphatic vascular density, which was higher than those of lymph nodes (P < 0.0001). Warthin's tumor is a true neoplastic epithelial proliferation associated with increased angiogenesis and lymphangiogenesis and induces reactive lymph node hyperplasia.

Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3

ObjectiveThe aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. Materials and methodsAn experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-κB immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Müllerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann–Whitney U and χ2 tests. ResultsWe found statistically significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration, stromal fibrosis scores, and NF-κB immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. ConclusionThese findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-κB pathway with resveratrol. We thought that the NF-κB pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Müllerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further.

The Protective Effect of Granulocyte Colony-Stimulating Factor on Endometrium and Ovary in a Rat Model of Diabetes Mellitus

Aims: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the endometrium and ovaries in an experimental diabetes mellitus (DM) rat model. Methods: A total of 18 female Sprague-Dawley albino mature rats (8 weeks, 200-220 g) were used in this study. Diabetes was induced by intraperitoneal (i.p.) injection of streptozocin randomly in 12 rats. No drug was administered to the remainder of the rats (control group, group 1, n = 6). The other 12 rats were randomly divided into 2 groups; 1 ml/kg i.p. saline was given as vehicle to group 2 (diabetic nontreated control group, n = 6) and 100 µg/kg/day of i.p. G-CSF was given to group 3 (G-CSF-treated group, n = 6) for 4 weeks. After 4 weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Results: The mean endometrial gland degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Ovarian follicle degeneration, stromal degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Plasma TGF-β and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimüllerian hormone levels were significantly lower in group 2 compared with groups 1 and 3. Conclusion: Glucose toxicity occurred severely in the ovaries and endometrium of the DM rats. After G-CSF treatment, ovarian and endometrial injury and fibrosis scores decreased significantly. The effects of G-CSF in rat models give hope to improved treatment of human DM complications such as premature ovarian failure and endometrial dysfunction.

Blackish Pigmentation of the Aorta in Patient with Alkaptonuria and Heyde's Syndrome

Alkaptonuria is an autosomal recessive trait resulting in an error of aromatic amino acids metabolism. Heyde's syndrome is a condition clustering together aortic valve stenosis and gastrointestinal bleeding from colonic angiodysplasia. At present, there is no report describing the association of the latter two syndromes in the same patient. Here we present the case of a patient with severe aortic stenosis, alkaptonuria, and Heyde's syndrome. The patient underwent aortic valve replacement by means of a valvular bioprosthesis and the histological examination of the aortic cusps revealed calcific degeneration. This was associated with stromal degeneration characterized by extra-cellular deposition of granular, brownish-pigmented material along with macrophages and multiple foci of calfication showing the same brownish pigmentation. This configuration represents the typical pattern of homogentisic acid accumulation known as ochronosis. The postoperative course was uneventful and the echocardiographic follow-up at 6 months postoperatively showed good-functioning of the aortic valve bioprosthesis.

Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to that observed in human casualties. However, a better understanding of the temporal changes that occur during the biphasic SM injury is crucial to mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of pathogenesis of the chronic SM injury over eight weeks. We confirm that MGK onset exhibits a biphasic trajectory involving corneal surface regeneration over the first two weeks, followed by the rapid development and progressive degeneration of corneal structure. Preclinical markers of corneal dysfunction were identified, including destabilization of the basal corneal epithelium, basement membrane zone abnormalities and stromal deformation. Clinical sequelae of MGK appeared abruptly three weeks after exposure, and included profound anterior edema, recurring corneal erosions, basement membrane disorganization, basal cell necrosis and stromal degeneration. Unlike resolved corneas, MGK corneas exhibited frustrated corneal wound repair, with significantly elevated histopathology scores. Increased lacrimation, disruption of the basement membrane and accumulation of pro-inflammatory mediators in the aqueous humor provide several mechanisms for corneal degeneration. These data suggest that the chronic injury is fundamentally distinct from the acute lesion, involving injury mechanisms that operate on different time scales and in different corneal tissues. Corneal edema appears to be the principal pathology of MGK, in part resulting from persistent necrosis of the basal corneal epithelium and deterioration of the basement membrane. The findings also provide a potential explanation as to why administration of anti-inflammatories transiently delays, but does not prevent, the development of MGK sequelae.

Cobblestone Lissencephaly in Schinzel-Giedion Syndrome

The brain of a 5-year-old boy with Schinzel-Giedion syndrome displayed a cobblestone appearance of orbital and lateral aspects of frontal lobes due to widespread glioneuronal meningeal heterotopia. Meningeal heterotopia consisted of scattered neurons, neurofilament positive axons, and myelinated fibers accompanied by striking astrocytic gliosis. The underlying cortex showed gaps in the pial basal lamina, distorted neuronal layering, and focal polymicrogyria. The number of capillaries appeared increased throughout the brain. Mild hydrocephalus was associated with a slight atrophy of corpus callosum as well as villous hyperplasia and marked stromal degeneration of the choroid plexus. Our findings suggest that Schinzel-Giedion syndrome may represent One more entity within enlarging spectrum of lissencephalic cortical dysplasia syndromes.

Pathological study of mycobacterium abscessus keratitis

To characterize the cytopathology, histopathology, immunohistochemistry and ultrastructural organization features of Mycobacterium abscessus keratitis. This retrospective case report included six cases with the lesions tissues scraped from acute phase of mycobacterium abscessus keratitis after corneal foreign body removal. Among the 6 scrapings, 4 were tested for Ziehl-Neelsen acid-fast staining and 3 were examined by transmission electron microscopy (TEM). The corneal tissues of 2 cases in chronic phase of the disease were collected during keratoplasty and were examined by pathological examination including hematoxylin-eosin (HE) staining, acid-fast staining, immunohistostaining and TEM. A single or fascicular red bacilli were observed after acid-fast staining in the four cases of corneal scrapings. The smear samples contained a large number of neutrophils and necrotic corneal epithelium and stroma tissue accompanying with a large number of mycobacteria that were positive for acid-fast staining scattered in and out of inflammatory cells. The corneal buttons obtained at keratoplasty in the 2 patients demonstrated corneal epithelial hyperplasia, stroma degeneration, necrosis and exelcosis, neutrophil and lymphocyte infiltration, neovascularization and fibrous hyperplasia, but no positive mycobacteria by Ziehl-Neelsen acid-fast staining. There were no CD4(+) or CD8(+) cells from immunohistochemistry examination. TEM of the corneal scrapings of the 3 cases showed phagocytosis of mycobacterium abscessus in mononuclear macrophage or neutrophils, inclusion compounds of small vacuoles and metachromatic granules in the thallium. TEM of corneal buttons of 2 cases showed slender rod-shaped mycobacteria with several to dozens of finely ground particles with high electron-dense, but no cell wall (L-form) or inclusion compounds. Mycobacterium abscessus keratitis presents acute purulent inflammatory changes in early stage and advances to chronic and non-specificity inflammation changes in late stage. L-formed mycobacterium abscessus make the disease protraction.

Unilateral Corneal Endothelial Dystrophy and Anterior Keratoconus

To describe a case of keratoconus and Fuchs' corneal endothelial dystrophy in the left eye with no corneal disease in the right eye. A 64-year-old woman presented with visual impairment in her left eye; computer-assisted topographic analysis and specular microscopy were performed in both eyes and left cornea was histopathologically examined. Keratoconus was diagnosed by slit-lamp examination, keratometry, and computer-assisted topographic analysis. Corneal endothelial dystrophy was diagnosed on the basis of clinical examination and specular microscopy. Histopathologic examination revealed a stromal degeneration typical of keratoconus and a non-guttae form of endothelial dystrophy. This is a rare case of unilateral corneal endothelial dystrophy and keratoconus.

Aggressive Natural Killer Cell Leukemia: Report of a Chinese Series and Review of the Literature

Aggressive natural killer cell leukemia (ANKL) is a rare Epstein-Barr virus (EBV)-associated fulminating disease that is widely disseminated at diagnosis. Because of its typically extranodal presentation, differing degrees of NK cell involvement, and varying bone marrow pathology, ANKL can be confused with a reactive process. These features, coupled with a rapidly fatal course, have hampered systematic study of the pathogenesis of ANKL. Nine cases of ANKL were diagnosed and characterized by a single laboratory over a 2-year period. Constant features at presentation included disseminated disease, high fever, bone marrow involvement, and a high lactate dehydrogenase index. All cases were positive for EBV early region protein and negative for latent membrane protein 1, and all had a germline T-cell receptor gene configuration. Peripheral blood counts were variable, with severe thrombocytopenia being the most frequently encountered abnormality (7 of 9 cases). Hematophagocytosis, dyserythropoiesis, and stromal degeneration were the most frequent findings in the bone marrow. Neoplastic cells in the bone marrow were consistently CD2+, CD56+, CD45+, CD34-, CD117-, CD4-, and surface CD3-. Most cases were HLA-DR+ (8/9) and CD8- (8/9). Complex clonal cytogenetic abnormalities were found in 8 of 9 cases. Because of its aggressive course, rapid and accurate diagnosis of ANKL is essential for a better understanding of the etiology, pathogenesis, and treatment of the disease.

“Steel Wool Keratopathy”

To introduce into the clinical nomenclature a sign frequently observed in our patients with persistent corneal inflammation associated with herpetic stromal keratitis. Case reports and review of the literature. Four representative patients with herpesvirus stromal keratitis are presented. Herpes simplex virus-1 (HSV-1) was confirmed by culture in 1 case and by polymerase chain reaction in a second case. In the remaining 2 cases, the diagnosis was made based on characteristic clinical findings for herpes simplex virus and varicella zoster virus (VZV). On clinical examination, all 4 representative cases of stromal keratitis revealed a well-defined, localized region of intertwined, metallic-like, polychromatic material in the corneal stroma, a sign we have termed steel wool keratopathy. We have only rarely observed this finding in patients with stromal keratitis not caused by a herpesvirus. Steel wool keratopathy seems to represent a focal region of stromal degeneration or deposition associated with chronic inflammation. Although we most often observe this finding in patients with stromal keratitis secondary to HSV or VZV, we cannot exclude the possibility that this sign represents the sequelae of chronic/recurrent inflammation rather than a specific pathologic response to herpetic antigens.

Chronic exposure to benzene results in a unique form of dysplasia

Hematotoxicity following chronic benzene exposure has been recognized for over a century, although the mechanism remains unknown. We describe a novel form of bone marrow dysplasia in 23 workers exposed to high concentrations of benzene. Distinguishing features of benzene-induced dysplasia include: marked dyserythropoiesis, eosinophilic dysplasia and abnormal cytoplasmic granulation of neutrophilic precursors. Hematophagocytosis, stromal degeneration and bone marrow hypoplasia are also seen. Severe bone marrow dysplasia is frequently accompanied by clonal T cell expansion and alterations in T lymphocyte subsets. No clonal cytogenetic abnormalities were observed. These results suggest that autoimmune-mediated bone marrow injury is an early or predisposing event in the pathogenesis of benzene-induced persistent hematopoietic disease.