Cutaneous Malignant Melanoma Presenting as an Isolated Splenic Metastasis: An Update.

Although the spleen is a highly vascularized organ, metastatic deposits from non-hematolymphoid solid malignancies are rare. This is reasoned to the inherent resistance of the splenic parenchyma to harbor metastases. The splenic capsule, lack of afferent lymphatics, contractile properties of the spleen, and the angular and gyroid course of the splenic artery form several barriers against the metastatic spread of malignant tumors. Moreover, the immune cells in the white and red pulps of the spleen have strong defensive ability against the tumor cells. Metastasis from solid tumors to the spleen often occurs only during widespread distant spread. Malignant melanoma is a rare but fatal malignancy. Isolated splenic metastasis from malignant melanoma is exceptionally rare. Studies that addressed the splenic metastasis from cutaneous malignant melanoma are scarce. This minireview was performed to address this subject. Here we present an overview of the clinicopathologic features of isolated splenic metastatic melanoma. The diagnostic biochemical markers in melanoma are also discussed.

An Unusual Solitary Fibrous Tumor of the Ischiorectal Region.

Solitary fibrous tumors (SFTs) are rare fibroblastic/myofibroblastic proliferations that occur in a wide range of anatomical sites. These tumors have nonspecific clinical presentations often with unpredictable biological behavior. SFTs can be slow growing low-risk tumors or rapidly growing high-risk tumors. They show a wide variety of histological features and typically are characterized by NAB2-STAT6 fusion. SFTs of the ischiorectal fossa are rare, with few studies reported in the literature to date. Here, we report a 90-year-old male who had a road traffic accident in October 2018. A pelvic computed tomography (CT) revealed a mass measuring 3.5 × 2.5 cm in the right ischiorectal fossa. Histopathology of the CT-guided biopsies confirmed the diagnosis of low-grade SFT. No surgical intervention was needed since the patient was asymptomatic. In January 2022, a follow-up CT showed a gradual increase in tumor size (5 × 3.5 × 3 cm), but not infiltrating the surrounding structures. However, the patient complained of constipation, which warranted a surgical excision of the mass. Subsequently, immunohistological examination reconfirmed the diagnosis of low-risk SFT. Here, we discussed the clinicopathological features of the case and the relevant literature about pelvic SFTs. In conclusion, SFTs should be considered in the differential diagnosis of any ischiorectal mass. It is recommended that tissue samples be obtained, and immunohistology should be performed.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

BACKGROUND: The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. AIMS: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. MATERIALS AND METHODS: Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). RESULTS: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). CONCLUSIONS: The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Primary Basidiobolomycosis of the Cecum in Immunocompetent Patients: Two Case Reports.

Colonic basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Primary cecal basidiobolomycosis is an exceptionally rare condition. The study describes two cases of primary basidiobolomycosis of the cecum in immunocompetent male and female patients (one each). The patients presented with fever, abdominal pain, weight loss, eosinophilia, and high erythrocyte sedimentation rates. Computed tomography revealed wall thickening and mass lesions involving the cecum, suggesting malignancy. Right hemicolectomies were performed to relieve the intestinal obstruction. On microscopy, there were destructive, transmural eosinophil-rich pyogranulomatous reactions with thin-walled, pauci-septated fungal elements surrounded by Splendore-Hoeppli bodies. The patients received antifungal drugs, with no evidence of dissemination or recurrence on follow-up. Primary cecal basidiobolomycosis in immunocompetent hosts is a rare occurrence. It oftentimes clinically masquerades malignant neoplasms and therefore its identification mandates its inclusion in the differential diagnosis of a colonic mass, equally both on the part of the clinicians and pathologists.

Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity.

The histopathologic diagnosis of prostate cancer (PCa) from biopsies is a current challenge if double or triple staining is needed. Therefore, there is an urgent need for development of a new reliable biomarker to diagnose PCa patients. We aimed to explore and compare the expression of TMTC4 in PCa cells and tissue specimens and evaluate its sensitivity and specificity. The expression of TMTC4 in PCa and normal prostate epithelial cells was determined by real-time PCR and Western blot analyses. Immunohistochemical (IHC) staining of TMTC4 was performed on tissues collected from PCa and benign prostatic hyperplasia (BPH). Our results show a high expression of TMTC4 on mRNA and protein levels in PCa versus BPH1 and normal cells (p < 0.05). IHC results show strong cytoplasmic expressions in PCa cases (p < 0.001) as compared to BPH cases. The overall accuracy as measured by the AUC was 1.0 (p < 0.001). The sensitivity and specificity of the protein were 100% and 96.6%, respectively. Taken together, we report a high TMTC4 expression in PCa cells and tissues and its ability to differentiate between PCa and BPH with high sensitivity and specificity. This finding can be carried over to clinical practice after its confirmation by further studies.

Incidence of Gastrointestinal Neuroendocrine Tumor: Case Series, Armed Forces Hospital Southern Region, Hospital-Based Tumor Board Registry.

Neuroendocrine tumors are aggressive and rare tumors which can occur almost everywhere in the body. The annual incidence of neuroendocrine tumors is 2.5-5 per 100000. We report seven cases of gastrointestinal neuroendocrine tumors which were diagnosed and treated at our hospital from the time period of 2016-2018 knowing that the total number of our hospital tumor board cases registry during the same period was 444 cases.

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.

In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H+ , K+ -ATPase ß-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.

Gastric metastases from invasive primary mucosal epithelioid malignant melanoma of the hard palate: report of the first case in the English literature.

Melanocytes arise from the neural crest and migrate to the epidermis, meninges, uveal tract and ectodermal mucosa. Normal gastric mucosa lacks melanocytes. A 64-year-old woman presented to us with nausea and vomiting. She had a past history of invasive primary mucosal epithelioid malignant melanoma of the hard palate 21 months ago, treated by a wide surgical excision. Gastroscopy revealed multiple punched out ulcers involving the stomach and the first part of duodenum. Immunohistology and clinicopathologic correlation established the diagnosis of metastatic gastric malignant melanoma. To our knowledge, this is the first report in the English literature about gastric metastases arising from primary palatal mucosal melanoma.

Assessment of malignancy rate in thyroid nodules according to the Bethesda system of fine-needle aspiration. Report from a tertiary center in the Southwestern region of Saudi Arabia.

OBJECTIVE: To determine the rates of malignancy of thyroid nodules in each standard cytologic diagnostic category of the Bethesda system. METHODS: In a retrospective cohort study from October 1998 to April 2007 at the Department of Pathology, Aseer Central Hospital, Southwestern region of Saudi Arabia, all cases of thyroid nodules that underwent preoperative cytologic examination by fine-needle aspiration (FNA) and concurrent postoperative histopathologic examination were included. All FNA diagnoses were reclassified using the thyroid FNA Bethesda reporting system, including non-diagnostic (insufficient), benign, atypical follicular lesion of undetermined significance (AFLUS), neoplasm, suspicious of malignancy, and malignant groups. The rate of malignancy based on final histopathologic evaluation was analyzed for each of these cytologic groups. RESULTS: A total of 323 thyroid fine needle aspiration cytology (FNAC) diagnoses were reclassified into non-diagnostic 6.2%, benign 57.3%, AFLUS 13.6%, follicular and Hurthle cell neoplasms 16.1%, suspicious of malignancy 1.5%, and malignant 5.3% groups. The corresponding rate of malignancy on histopathologic examination was as follows: 35% in the non-diagnostic group, 10.3% in the benign group, 15.9% in AFLUS group, 32.7% in follicular and Hurthle cell neoplasms, 60% in the suspicious of malignancy group, and 94% in the malignant group. CONCLUSION: Applying a standard terminology reporting system for thyroid FNA may enhance the communication between pathologists and clinicians, assists them to find out the rate of malignancy in each cytologic group, and facilitating a more consistent approach for patients' management.

Alterations of p53 and Bcl-2 protein expression in the recurrent laryngeal and pharyngeal squamous cell carcinoma.

BACKGROUND: Identification of molecular events of the recurrent squamous cell carcinoma (SCC) of the larynx and pharynx may aid in refining treatment strategies and improving outcome. The underlying molecular events of these recurrent tumors involve alterations in the tumor suppressor genes (p53) and protooncogenes (Bcl-2). We hypothesize that the development of these recurrent tumors involves alterations of the p53 and Bcl-2 proteins. METHODS: To test this hypothesis, 15 laryngeal and pharyngeal biopsy specimens obtained from 15 patients with recurrent laryngeal or pharyngeal SCC with different grades (II-IV) were immunostained for p53 and Bcl-2 protein expression. RESULTS: Examination of the percentage of positive cells in the normal mucosa and SCC, respectively, showed significant up-regulation of p53 (0.0 ± 0.0 vs 51.8 ± 5.9, P = .00) and Bcl-2 protein expression (36.5 ± 3.5 vs 74.6 ± 1.9, P = .00). CONCLUSIONS: Alterations of the p53 and Bcl-2 proteins occur during the development of recurrent SCC. Additional studies are needed to confirm and extend our results.

Microvillous inclusion disease: a clinicopathologic study of 17 cases from the UK.

BACKGROUND: Microvillous inclusion disease (MVID) is a rare congenital disease producing intractable secretory diarrhea in early infancy. It is characterized by diffuse intestinal villous atrophy with no inflammatory reaction. Ultrastructural identification of apical microvillous inclusions in the surface enterocytes is diagnostic. However, there is difficulty in the diagnosis of MVID due to the existence of variants (e.g., microvillous dystrophy), possible disease resolution, and tissue orientation for electron microscopy (EM). The authors analyzed materials from 4 patients with MVID from a single institution. The morphologic features, distribution of lesions, biomarkers, and complementary ultrastructural characteristics were studied. DESIGN: Materials of MVID cases were collected from 6 different hospitals in the United Kingdom between 1990 and 2008. Epidemiological data, including age range, median, mode, sex ratios, and follow-up, were retrieved. All intestinal biopsy specimens were analyzed histologically, histochemically (for PAS, n = 17), immunohistochemically (for CD10, n = 2 and polyclonal CEA, n = 4), and ultrastructurally (n = 9). RESULTS: Ultrastructurally, apical microvillous inclusions in surface enterocytes in duodenal biopsies were identified in all cases, while 1 case had variant morphology (microvillous dystrophy and very occasionally atypical microvillous inclusions). Tissue orientation for EM was supportive for identification of inclusions in apical enterocytes. Morphologically, a bubbly vacuolated appearance of the apical cytoplasm with extensive or patchy absence of the brush border with occasional cytoplasm inclusions was observed in the enterocytes. Some of these changes vaguely resembled gastric mucin cell metaplasia. Architecturally, villous blunting with either crypt hypoplasia or hyperplasia and absence of inflammation were common findings. The epithelial changes were also found in colon biopsies. PAS, CD10, and p-CEA showed a bright apical cytoplasmic blush/staining, which correlated ultrastructurally with apical granules with inclusions of variable electron density in all cases. These stains also highlighted the targetoid inclusions. CONCLUSION: Besides electron microscopy identification of inclusions, the light microscopic morphological features together with the biomarker studies highlighting the apical cytoplasmic blush are quite unique and diagnostic of MVID. Furthermore, it is the opinion of the authors that a diagnosis of MVID can be made without electron microscopy.

Primary meningioma of the nasal septum: a case report and review of literature.

Extracranial meningiomas are rare tumors that usually represent extensions from intracranial lesions. Here, we report a case of primary meningioma of the nasal septum. A 60-year-old man presented with nasal obstruction and postnasal drip. On examination he had a mass in the nasal cavity. Computed tomography studies revealed absence of intracranial extensions. The mass was successfully excised and the histologic diagnosis of meningioma was established. This report documents what we believe to be the first case (in English medical literature) of an extracranial meningioma, involving the nasal septum. The clinicopathologic features and pathogenesis of the primary nasal meningioma is briefly discussed.

Pulmonary renal syndrome associated with Wegener's granulomatosis: a case report and review of literature.

Pulmonary renal syndromes are rare but serious complications of systemic vasculitis. The majority of these cases are related to ANCA-associated vasculitis. These syndromes represent a combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. Here we report a case of 21-year-old female with a clinical picture of community-acquired pneumonia that rapidly evolved to pulmonary hemorrhage and acute renal failure. Combined pulse steroid treatment, immunosuppressive treatment, and plasmapheresis were instituted and resulted in the improvement of the patient. The diagnosis of Wegener's granulomatosis was established based on the clinical and serological findings (positive cANCA). Here we review the relevant literature on pulmonary renal syndromes associated with Wegener's granulomatosis and discuss their diverse clinicopathologic features.

Primary peritoneal malignant mixed mesodermal (Müllerian) tumor.

AIMS AND BACKGROUND: Malignant mixed mesodermal tumor (MMMT) is a biphasic neoplasm (carcinosarcoma) composed of both epithelial and mesenchymal elements. Extragenital MMMT, including primary peritoneal MMMT, is an extremely rare tumor with features consistent with its origin from the secondary Müllerian system. The neoplastic elements of extragenital MMMT presumably arise directly from the mesothelium or submesothelial stroma and hence parallel the biphasic pattern of the genital (uterine or ovarian) counterpart. METHODS AND STUDY DESIGN: Here we report on the clinical, pathological, and immunohistochemical features of a case of peritoneal MMMT in a 65-year-old woman. The patient presented with abdominal fullness and pain. Gynecological examination revealed a huge pelvic abdominal mass. On histology, the tumor consisted of poorly differentiated carcinomatous and sarcomatous (rhabdomyosarcoma) components. Further immunohistochemical analysis revealed positive reactivity for both epithelial (cytokeratin and epithelial membrane antigen) and mesenchymal (vimentin, S-100, and desmin) markers. The patient refused treatment and died of the disease three months later. RESULTS AND CONCLUSIONS: Based on the present case and on previous studies, primary peritoneal MMMT seems to be a rare but highly malignant neoplasm with an aggressive behavior and poor prognosis. Its exact origin, histogenesis and molecular alterations are poorly understood.

Juvenile pleomorphic adenoma of the cheek: a case report and review of literature.

Pleomorphic adenoma, also called benign mixed tumor, is the most common tumor of the salivary glands. About 90% of these tumors occur in the parotid gland and 10% in the minor salivary glands. The most common sites of pleomorphic adenoma of the minor salivary glands are the palates followed by lips and cheeks. Other rare sites include the throat, floor of the mouth, tongue, tonsil, pharynx, retromolar area and nasal cavity. In children, intraoral pleomorphic adenomas of the cheek are extremely rare with only three cases reported to date. Here we report a case of pleomorphic adenoma of minor salivary glands of the cheek in a 17-year-old girl. The mass was removed by wide local excision with adequate margins, and after a follow-up period of three years there were no recurrences. To conclude, pleomorphic adenoma should be considered in the differential diagnosis of cheek masses in youngsters. Wide local excision is to be recommended as the treatment of choice. A close follow-up is necessary postoperatively.

Analysis of p53, BCL-2 and epidermal growth factor receptor protein expression in the partial and complete hydatidiform moles.

BACKGROUND: Hydatidiform moles are gestational trophoblastic neoplasms that include both partial and complete moles. Apoptosis plays important roles in the normal placental morphogenesis and in the pathogenesis of the gestational trophoblastic neoplasia. TP53 is a tumor suppressor gene (pro-apoptotic molecule) that maintains genomic stability either by inducing cell-cycle arrest or apoptosis. BCL-2 is a proto-oncogene (a pro-survival molecule) that enhances growth and survival of cells. Epidermal growth factor receptor (EGF-R) is a transmembrane glycoprotein, which can bind and be activated by various ligands. It stimulates cell division and differentiation. OBJECTIVES: The study examined the expression pattern of p53, BCL-2 and EGF-R proteins in the hydatidiform moles. MATERIALS AND METHODS: Immunoperoxidase-staining methods and specific monoclonal antibodies were used to examine the expression of p53, BCL-2 and EGF-R in partial and complete moles (10 cases each). Trophoblastic tissue from first trimester terminations of pregnancy (non-molar tissue, 20 specimens) served as a control group. The data were evaluated to determine variations in the expression pattern among the molar and non-molar tissues. RESULTS: The expression patterns of these proteins varied between first trimester pregnancy terminations and molar placentas. Chorionic villi from first trimester pregnancy terminations showed strong expression of BCL-2 and EGF-R protein. In molar chorionic villi, there was a moderate expression of BCL-2 and EGF-R proteins. p53 protein expression was absent in first trimester pregnancy terminations and a partial mole whereas moderate nuclear positivity was found in the complete mole. There was a significant positive correlation between BCL-2 and EGF-R protein expression whereas inverse correlation exists between p53 and BCL-2/EGF-R protein expression. CONCLUSIONS: The prominent expression of both EGF-R and BCL-2 (indicators of cell proliferation/survival) in the molar trophoblast suggests their involvement in the development of these tumors. The lack of significant p53 protein overexpression suggests the lack of underlying p53 mutations in hydatidiform moles.

Decidual immune cell infiltrate in hydatidiform mole.

BACKGROUND: Hydatidiform mole is a gestational trophoblastic disease characterized by proliferation of the pregnancy-associated trophoblastic tissue. Complete hydatidiform mole is an entirely paternally derived lesion, and therefore, represents complete intrauterine allografts that can induce an altered maternal immune response Hypothesis: Here, we hypothesize that "the development of hydatidiform moles is associated with numeric alterations of the decidual immune cell infiltrate." MATERIALS AND METHODS: A total of 30 specimens (decidual tissue), entailing normal first trimester pregnancy terminations and complete hydatidiform moles (15 cases, each), were evaluated for immune cell infiltrate using immunohistological methods and monoclonal antibodies (CD20, CD68, and CD3 for B cells, histiocytes/dendritic cells, and T cells, respectively). RESULTS: Groups of immune cells were seen in the decidual tissue of first trimester normal pregnancy terminations and hydatidiform moles. Compared to the decidual tissue of first trimester normal pregnancy terminations, the mean counts of the immune cells were statistically significantly higher (p< 0.05) in the decidual tissue of the hydatidiform moles (0.33 +/- 0.21 vs. 1.66 +/- 0.21 for CD20(+)B cells; 9.80 +/- 1.57 vs. 13.14 +/- 1.16 for CD68(+) cells; and 12.92 +/- 3.46 vs. 23.85 +/- 1.22 for CD3(+) cells for decidual tissue without and with molar changes, respectively). CONCLUSIONS: Hydatidiform moles are associated with numeric alterations of immune cell infiltrate. The numeric dominance of immune cells in the hydatidiform moles may reflect either non-specific or specific immunological processes. The possible pathogenetic and prognostic ramifications of our findings are open for further investigations.

Mucocutaneous Splendore-Hoeppli phenomenon.

Splendore-Hoeppli phenomenon (asteroid bodies) is the in vivo formation of intensely eosinophilic material (radiate, star-like, asteroid or club-shaped configurations) around microorganisms (fungi, bacteria and parasites) or biologically inert substances. This study presents a literature review concerning Splendore-Hoeppli reaction in the mucocutaneous diseases. It examines the histopathological features, nature and differential diagnosis of this reaction. It also discusses the mucocutaneous infections and the non-infective diseases associated with it. Available studies indicate that several mucocutaneous infections can generate Splendore-Hoeppli reaction. The fungal infections include sporotrichosis, pityrosporum folliculitis, zygomycosis, candidiasis, aspergillosis and blastomycosis. The bacterial infections include botryomycosis, nocardiosis and actinomycosis. The parasitic conditions include orbital pythiosis, strongyloidiasis, schistosomiasis and cutaneous larva migrans. In addition, Splendore-Hoeppli reaction may be seen with non-infective pathology such as hypereosinophilic syndrome and allergic conjunctival granulomas. The Splendore-Hoeppli reaction material comprises antigen-antibody complex, tissue debris and fibrin. Although the exact nature of this reaction is unknown, it is thought to be a localized immunological response to an antigen-antibody precipitate related to fungi, parasites, bacteria or inert materials. The characteristic formation of the peribacterial or perifungal Splendore-Hoeppli reaction probably prevents phagocytosis and intracellular killing of the insulting agent leading to chronicity of infection. To conclude, Splendore-Hoeppli reaction is a tell tale of a spectrum of infections and reactive conditions. The molecular pathways involved in the development of this reaction are open for future investigations.

Melatonin and roentgen irradiation-induced acute radiation enteritis in Albino rats: an animal model.

BACKGROUND: Roentgen irradiation can affect normal cells, especially the rapidly growing ones such as the mucosal epithelial cells of the small intestine. The small intestine is the most radiosensitive gastrointestinal organ and patients receiving radiotherapy directed to the abdomen or pelvis may develop radiation enteritis. Although roentgen rays are widely used for both imaging and therapeutic purposes, our knowledge about the morphological changes associated with radiation enteritis is lacking. HYPOTHESIS: This study tries to tests the hypothesis that "the intake of melatonin can minimize the morphological features of cell damage associated with radiation enteritis". OBJECTIVES AND METHODS: We performed this investigation to test our hypothesis and to examine the possible radioprotective effects of melatonin in acute radiation enteritis. To achieve these goals, an animal model consisting of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (X-ray irradiation, 8 Grays); Group 3, X-ray irradiated-pretreated with solvent (ethanol and phosphate buffered saline); Group 4, non-irradiated-group treated with melatonin, and Group 5, X-ray irradiated-pretreated with melatonin. The small intestines were evaluated for gross (macroscopic), histological, morphometric (light microscopy), and ultrastructural changes (transmission electron microscopy). RESULTS: We found morphological variations among the non-irradiated-group, X-ray irradiated-group and X-ray irradiated-intestines of the animals pretreated with melatonin. The development of acute radiation enteritis in X-ray irradiated-group (Groups 2 and 3) was associated with symptoms of enteritis (diarrhea and abdominal distention) and histological features of mucosal injury (mucosal ulceration, necrosis of the epithelial cells). There was a significant reduction of the morphometric parameters (villous count, villous height, crypt height and villous/crypt height ratio). Moreover, the ultrastructural features of cell damage were evident including: apoptosis, lack of parallel arrangement of the microvilli, loss of the covering glycocalyx, desquamation of the microvilli, vacuolation of the apical parts of the cells, dilatation of the rough endoplasmic reticulum, and damage of the mitochondrial cristae. In the non-irradiated-group and in X-ray irradiated-intestines of the animals pretreated with melatonin (Group 5), these changes were absent and the intestinal mucosal structure was preserved. CONCLUSION: Administration of melatonin prior to irradiation can protect the intestine against X-rays destructive effects, i.e. radiation enteritis. The clinical applications of these observations await further studies.

Extracutaneous malignant melanomas.

Extracutaneous malignant melanomas are rare tumors with vexing clinical presentation and grim prognosis. Only 4%-5% of all primary melanomas do not arise from the skin. These tumors are almost uniformly fatal, even in 2006. Although a fairly good number of these lesions were reported in the literature, the lack of a side-by-side analysis of these studies has resulted in tentative conclusions that merely offer a first glimpse at the clinicopathologic diversity of these lesions. To remedy this issue, this article took an aim at presenting a literature review concerning extracutaneous malignant melanomas. It also reports several cases of extracutaneous melanomas, which I came across in my 15 years of surgical and molecular pathology practice. The study raises several notions. Extracutaneous malignant melanomas are rare but extremely aggressive lesions with a grim outcome. They include ocular, metastatic, anorectal, mucosal, nail beds, conjunctival, vaginal, urogenital, orbital, esophageal, and leptomeningial malignant melanomas. The development of these lesions lacks an association with sun damage, family history, or precursor nevi. These lesions cause considerable diagnostic consternation and their distinction from other types of tumors (such as undifferentiated carcinomas, high-grade sarcomas, and lymphomas) is critical both from a diagnostic and prognostic point of view. In the proper clinical, histological, and cytological context, immunopositivity for S100 protein, HMB45, and vimentin allows the distinction of these malignant melanomas from other histologically similar malignancies. To conclude, extracutaneous melanoma should be considered while undifferentiated neoplasms, especially those displaying prominent eosinophilic nucleoli, and the coexistence of epithelioid and spindle cells. Special staining and immunohistochemistry should be resorted to establish the diagnosis.