Evaluation of microsatellite instability in routine examinations of surgical samples.

CONTEXT: Approximately 20%-30% of colon cancer cases have a hereditary basis. The genetic defect may involve mismatch repair (MMR) genes, which results in microsatellite instability (MSI). MMR-deficient colorectal cancer may occur due to germline mutation (Lynch syndrome) or be a sporadic one. A tumor's histological features, supported by a panel of immunohistochemistry stains, enables pathologists to assess the MMR status, which in turn has beneficial effects on clinical management. AIMS: We aimed to show the relations between histopathological features identified during routine examinations and MMR genes' mutations. METHODS AND MATERIAL: We reviewed retrospectively the material of the Department of Pathology fulfilling the revised Bethesda Guidelines. STATISTICAL ANALYSIS USED: We used Chi-square test, Spearman test, and epidemiological analysis. RESULTS: For the PMS2 gene, the positive predictive value (PPV) indicates that 91% of cases neither present any histological lesions nor have genetic abnormalities. The negative predictive value (NPV) indicates that only 50% of cases have both histological and genetic changes. For the MSH6 gene, the PPV indicates that 85% of tumors without specific histological features do not have genetic abnormalities. CONCLUSIONS: We advise universal staining for MLH1, MSH2, MSH6, and PMS2 in every newly diagnosed colon cancer, but due to costly analyses we suggest a protocol for the selection of cases for MMR examinations.

Histopathological Examination may be Useful for Assessment of Fibrosis and Lipomatosis of Pancreas Allograft Prior to Solid Organ Transplantation.

BACKGROUND: The results of pancreas transplantation depend in a large degree on appropriate pancreas allograft donor selection. Several risk factors of early surgical complications or pancreas allograft loss following transplantation have been identified, but the final decision on pancreas harvesting for transplantation belongs to the surgeon. In the present study we aimed to assess whether histopathological examination may be utilized for detection of fibrosis and lipomatosis in tissue from a potential pancreas allograft. Additionally, we aimed to test whether presence of pancreatic fibrosis and lipomatosis may be explained solely by donor age and/or body mass index (BMI). MATERIAL AND METHODS: Pancreata retrieved from 50 deceased organ donors referred to our institution and not transplanted between 2010 and 2013 were used for the present study. Tissue samples were excised from pancreata, fixed in formalin, and embedded in paraffin. Presence and intensity of pancreatic fibrosis and lipomatosis were assessed semi-quantitatively. RESULTS: Fibrosis was found in the majority of study samples (72%), but it was usually mild or moderate. Lipomatosis was present in 34% of the study cases. Presence of fibrosis was more frequent in older donors, but was still not rare in donors under 40 years old. Presence of lipomatosis did not seem to be significantly related to donor age. Neither pancreatic fibrosis nor lipomatosis was related to donor BMI. CONCLUSIONS: There is no clear relationship between histological parenchymal changes in potential pancreas allograft and donor age and BMI. Histopathological assessment of pancreatic fibrosis and/or lipomatosis can potentially facilitate decision making on pancreas allograft acceptance for solid organ transplantation.

Clear cell carcinoma derived from an endometriosis focus in a scar after a caesarean section--a case report and literature review.

Endometriosis is defined as the occurrence of endometrial glands and endometrial stromal cells outside their typical localization within the uterus. Malignant transformation of endometriosis foci in a scar after a caesarean section (cc) is very rare--until 2013 (in a span of 40 years), about 40 such cases have been described. In our article, we describe a case of a 42-year-old woman with a tumour localized in a scar after a caesarean section. The tumour was diagnosed as clear cell carcinoma derived from an endometriosis focus. The long time interval--17 years in average (from 3 to 39 years) between the surgery (cesarean section in most cases) and the tumor diagnosis is characteristic. In the case we describe, the patient was diagnosed 16 years after the endometriosis focus in the scar had arised. Even though endometriosis is a benign lesion, it has many features distinctive for invasive carcinoma; it may itself undergo a malignant transformation as well as increase the risk of endometrial carcinoma or clear cell ovarian carcinoma. Maybe in future, more exhaustive studies will allow establishing a therapeutic protocol in patients with extra-ovarian malignant transformation of endometriosis foci.

Inflammatory myofibroblastic tumor of the bladder - an unexpected case coexisting with an ovarian teratoma.

Inflammatory myofibroblastic tumors (IMTs) mainly occur in children and young adults, usually in the first two decades of life. IMT-type tumors belong to neoplasms of an intermediate biologic potential with considerable rate of local recurrence and in some cases that able to create metastases. Presented case is the first IMT coexisting with the other neoplasm. In our paper we are going to present a peculiar case of an IMT of the bladder coexisting with an ovarian teratoma, and to discuss its pathogenesis, histological picture and differential diagnosis. A 19-year-old female was admitted to the Gynecological Department and during the surgery, two independent, non-adjacent tumors were found. To settle the diagnosis, a FISH examination with the ALK1 break apart probe was carried out. It confirmed the rearrangement of the chromosome 2p23. Morphologic and immunophenotypic similarities between an IMT and other malignant tumors of the bladder may lead to diagnostic errors and an unnecessary radical cystectomy as a result. The therapy of choice is only total excision of the tumor. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1937487606122622.

"Mistletoe sign": probably a new dermoscopic descriptor for melanoma in situ and melanocytic junctional nevus in the inflammatory stage.

Melanomas in situ (MIS) are difficult to diagnose as they lack well-established, dermoscopic descriptors. In numerous clinical cases, there are no definitive differentiating criteria between atypical nevus and melanoma in situ. So far, no digital dermoscopic criteria have been developed which can clearly distinguish atypical naevi from MIS. It is necessary to search for predictors of MIS and clinically suspected skin lesions in dermoscopy. We present 2 patients diagnosed with and treated for melanoma in situ and junctional nevus in its inflammatory stage. This includes a new morphological structure in dermoscopy known as the "mistletoe sign". Below, we have described dermoscopic pictures, with appropriate histopathology, for patients with the "mistletoe sign". Dermoscopy in two cases revealed multiple, well-circumscribed areas, consisting of non-uniform, sometimes pseudo-dichotomously branched structures, mimicking pseudopods, which were not reticular, arising from overall reticular or homogenous patterns resembling the mistletoe. Due to the fact that this is one of the several reports of its kind, further research and observation are still necessary. The "mistletoe sign" may be a descriptor of the melanocytic nevus in the inflammatory stage and the melanoma in situ; however, further studies are necessary.

An atypical leiomyoadenomatoid tumor of the uterus--a case report and literature review.

UNLABELLED: In this study, we describe morphological and immunohistochemical features of a mixed tumor (atypical leiomyoadenomatoid tumor - LMAT) localized in the body of the uterus. AIM OF STUDY: LMAT-type tumors are very rare and only 5 cases have been described in the literature so far therefore this case report seems particularly noteworthy. MATERIALS AND METHODS: A 57-year-old patient was admitted to the Gynecology and Obstetrics Unit, Brothers of Mercy Hospital in Katowice for hysterectomy with bilateral salpingo-oophorectomy due to uterine myomata. The macroscopic examination of the surgical material revealed a polycystic tumor 5 cm in diameter with gelatinous contents and grey fibrous areas. The patient was discharged on postoperative day 4, in good general condition. A histological diagnosis of an atypical leiomyoadenomatoid tumor was established on the basis of the tissue material.

Reduction of post-traumatic neuroma and epineural scar formation in rat sciatic nerve by application of microcrystallic chitosan.

Injury of peripheral nerve is associated with the development of post-traumatic neuroma at the end of the proximal stump, often being the origin of neuropathic pain. This type of pain is therapy-resistant and therefore extremely nagging for patients. We examined the influence of the microcrystallic chitosan gel applied to the proximal stump of totally transected sciatic nerve on the neuroma formation and neuropathic pain development in rats. In 14 rats, right sciatic nerve was transected and the distal stump was removed to avoid spontaneous rejoining. In the chitosan (experimental) group (n = 7), the proximal stump was covered with a thin layer of the microcrystallic chitosan gel. In control animals (n = 7), the cut nerve was left unsecured. Autotomy, an animal model of neuropathic pain, was monitored daily for 20 weeks following surgery. Then, the animals were perfused transcardially and the proximal stumps of sciatic nerves were dissected and subjected to histologic evaluation. The presence, size, and characteristics of neuromas as well as extraneural fibrosis were examined. In chitosan group, the incidence and the size of the neuroma were markedly reduced, as compared with the control group; however, there was no difference in autotomy behavior between groups. In addition, extraneural fibrosis was significantly reduced in chitosan group when compared to the control group. The results demonstrate beneficial influence of microcrystallic chitosan applied to the site of nerve transection on the development of post-traumatic neuroma and reduction of extraneural fibrosis, however without reduction of neuropathic pain.

Primary pituitary lymphoma.

Primary CNS lymphoma (PCNSL) is now thought to constitute 3% of all intracranial neoplasms. PCNSL occurrence in the sella turcica region is an extremely rare finding. We present a 37-year-old male with primary pituitary lymphoma treated in our department. The patient, who had had no previous illnesses, was admitted to the hospital because of bilateral blurred vision. Findings on physical examination were normal except for temporal parts of field of vision deficit. No abnormalities were found in his bilateral ocular movement, facial sensory function or motor function. His blood count and biochemical profile were normal. Basic hormonal studies revealed no symptoms of panhypopituitarism. MRI demonstrated a large intrasellar mass with supra- and parasellar extension. MRS revealed decrease in NAA/tCr proportion and increase in Cho/NAA and Cho/tCr proportions. Endoscopic surgery was performed using the transsphenoidal approach. Histopathological examination demonstrated a large B-cell lymphoma. The patient received 6 cycles of CHOP chemotherapy. He was also irradiated with 6 MV photons to the whole brain to a total dose of 40 Gy and then there was a boost to the tumour to a total dose of 50 Gy. Next he was reoperated on with the fronto-temporo-sphenoidal craniotomy approach and subtotal resection of the tumour was performed. After the treatment the visual disturbances significantly decreased. Control MRI revealed a stable remnant of the tumour. Nowadays the patient has 52 months' follow-up and he has only a stable, slight visual field deficit on the upper temporal side of the right eye.

Papillary pineocytoma in child: a case report.

BACKGROUND: Papillary pineocytoma is an extremely rare tumor usually with a poor outcome. CASE REPORT: We report a case of a 10-year-old-girl with pineal gland tumor and obstructive hydrocephalus diagnosed using MRI. The child was successful treated by insertion of a ventriculoperitoneal shunt and consecutive tumor resection by supracerebellar-infratentorial approach. Histopathological examination showed a papillary structure of the pineocytoma. As such, tumors are considered to be aggressive the child was subjected to radio- and chemotherapy. CONCLUSION: At six year follow-up after surgery, the patient is symptom-free and the MRI shows no tumor recurrence.

Atypical features of dementia in a patient with Creutzfeldt-Jakob disease.

BACKGROUND: This article describes a Polish patient (female, right-handed, age 68 at onset) diagnosed with the Heidenhain variant of Creutzfeldt-Jakob Disease (HvCJD), characterized clinically by isolated visual disturbances with no ocular dysfunction prior to the development of myoclonus and other symptoms of CJD. CASE REPORT: Nothing in the history pointed to iatrogenic or acquired CJD, and genetic testing ruled out familial CJD. The neuroradiological picture (MRI) showed non-specific features of cerebral atrophy (cortical and subcortical). An EEG revealed periodic triphasic sharp waves, particularly in the occipital lobes, and myoclonus occurring synchronically with generalized periodic epileptiform discharges. Comprehensive neuropsychological testing documented rapidly progressive dementia, with dysgraphia and aphasia deteriorating to organic mutism. Post-mortem neuropathological examination confirmed spongiform encephalopathy, especially in occipital cortex, with amyloid plaques but without neurofibrillary tangles. CONCLUSIONS: Over the crucial 6-week period the patient went from "Mild Cognitive Impairment" to a status resembling the final stages of Alzheimer's disease, without any evidence of a CVA. The only aspect of this case that does not fit the usual criteria for the Heidenhain variant is the fact that the patient survived over a year in a persistent vegetative state. Ophthalmologists and family physicians should be aware of the possibility of HvCJD in any patient over 60 presenting with otherwise inexplicable visual disturbances in the absence of significant ocular pathology, even when other symptoms of dementia may not be immediately noticeable.

Aneurysmal bone cyst of the orbit.

We report the case of an aneurysmal bone cyst of the left orbital roof in a 12-year-old boy who presented proptosis of the left eye and painless swelling of the left orbital rim. A 3-cm-large tumor developed in less than 3 months, with first visible signs about 2 months after a minor head injury. Radiologically, the lesion was osteolytic and multicystic. The cyst, filled with hematic fluid, was surgically removed via left frontal craniotomy and a simple curettage with high-speed bur. The patient recovered well and has been in good health throughout 14 months of follow-up.

Use of monoclonal anti-EGFR antibody in the radioimmunotherapy of malignant gliomas in the context of EGFR expression in grade III and IV tumors.

We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

Prevention of painful neuromas by oblique transection of peripheral nerves.

OBJECT: Neuroma formation often occurs at the proximal stump of the transected nerve, complicating the healing process after gap injuries or nerve biopsies. Most such neuromas cause therapy-resistant neuropathic pain. The purpose of this study was to determine whether oblique transection of the proximal stump of the sciatic nerve can prevent neuroma formation. METHODS: The sciatic nerves of 10 rats were transected unilaterally at an angle of 30 degrees, and the peripheral segments of the nerves were removed. In 10 control animals the sciatic nerves were transected at a perpendicular angle. Twenty weeks after surgery the nerves were reexposed and collected. The presence of neuromas was determined by two board certified pathologists on the basis of histopathological evaluations. CONCLUSIONS: The oblique transection of peripheral nerves, contrary to perpendicularly transected nerves, is rarely followed by classic neuroma development. Moreover, neuropathic pain is significantly reduced compared with that following the traditional method of nerve transection.

Non-neoplastic, degenerative brain pathologies and fibroses diagnosed on the basis of ultra-small samples obtained by stereotactic biopsy.

Brain biopsy and other stereotactic procedures have evolved over the last decades. Recently, the morbidity and mortality decreased radically along with an increase in the number of successful histopathological diagnoses. Therefore, applications of appropriate treatments in neoplastic brain pathologies are now possible, especially of those located in deep regions. Stereotactic biopsy may also be used as a diagnostic method followed by appropriate management in conditions where a non-neoplastic pathology is suspected. Between December 2000 and February 2004, we performed 116 stereotactic procedures based on the system of stereotactic planning and Brain-Lab treatment, which was equipped with automatic CT/MR image fusion software. In this report, we have focused on 10 cases of non-neoplastic brain pathologies diagnosed on the basis of ultra-small samples obtained from stereotactic biopsy. Among them there were 4 cases of gliosis, 3 cases of brain degenerative disorders, 2 cases of hippocampal fibroses, and 1 case of normal brain tissue. We have presented all these cases in detail by discussing their histology, clinical manifestations, localisation, management and follow-up.

Correlation of facial nerve paresis and histopathological type of vestibular schwannoma.

The objective of the study was to evaluate the dependence of facial nerve paresis, as a symptom of cerebellopontine angle tumour, on the histopathological subtype of vestibular schwannoma, diagnosed from a post-operative histopathological examination. We retrospectively analysed 91 surgically treated patients with vestibular schwannoma. We studied the histopathological subtype and the preoperative condition of the facial nerve. The following WHO 2000 subtypes were distinguished: neurinoma cellular (51 cases), neurinoma conventional (23 cases), neurinoma ancient (11 cases), (other types: 2 neurofibroma and 2 ganglioneuroma). We analysed the dependence of facial nerve paresis on the histological subtype of tumours and their sizes. The analysis was based on the traditional classification: Antoni A (11 cases), Antoni B (12 cases) Antoni A/B (23 cases) and Antoni B/A (40 cases). 30 patients (30%) in the analysed group had paresis of the facial nerve preoperatively. Preoperative facial paresis occurred frequently in subtypes "cellular" and Antoni B, and rarely in subtypes conventional and Antoni A and B/A. In the small tumour cases (up to 20 mm), facial nerve paresis occurred frequently in subtypes cellular and conventional, as well as in Antoni A and A/B.

Stereotactic methods in interdisciplinary diagnosis and treatment of posterior fossa tumours.

For over 2 years, we have had access to latest generation apparatus and software for planning and stereotactic treatment as well as for x-rays treatment. Until now, we have carried out over 100 procedures. These included 52 stereotactic biopsies of neoplasms, some of them located within the structures of the posterior fossa. In this report, we have discussed the possibilities and effectiveness of diagnosis and treatment of tumours located in different structures, including posterior cave. In the study, we used stereotactic methods. We have described biopsies of the following tumours: cerebellar hemisphere tumour (diagnosed as "metastatic atypic planoepitheliale carcinoma" in a patient with coexisting orbit lymphoma), a bifocal lesion (located in cerebellar hemisphere and cerebellar peduncle, diagnosed as pilocytic astrocytoma of WHO malignancy grade II/III), and lesion (located in the pons, diagnosed as pilocytic astrocytoma WHO grade II).