5th European Conference on Clinical and Medical Case Reports September 07-08, 2017 Paris, France

Brian Zeman is a medical specialist in Rehabilitation Medicine practising in Sydney. He completed his medical degree at UNSW and then specialist training with the ACRM becoming one of the first four graduates. The ACRM later became a Faculty in the RACP. He has presented papers overseas on various subjects and is involved in medical student teaching as Lecturer. As well he is Clinical Supervisor for specialist training in rehabiliation medicine. He has interests in neurological rehabilitation, burns rehabilitation and medicolegal reports.

Ms M is a 42 year old woman with cerebral palsy affecting her mobility and speech. She was independent in the community and\r\nworking. She also had unrelated chronic asthma and after an exacerbation was prescribed prednisone. She then developed\r\npsychosis gradually over four weeks. The prednisone was stopped and she was prescribed an antipsychotic. She then developed\r\nextrapyramidal reaction causing torticollis and limb spasm. The antipyschotic was ceased and she was prescribed Benztropine.\r\nShe did not improve and remained hospitalised. She had Botulinum toxin injections to the neck and later leg as well as extensive\r\nphysiotherapy with gradual improvement. There was some improvement but not to previous mobility levels. About two monhts later,\r\nshe again gradually developed psychosis with auditory and visual hallucinations. She had extensive investigations but there were no\r\nobvious causes. Management of the psychosis with medications has been difficult and she required admission to psychiatric unit to\r\nhave these monitored. Was the psychosis due to triggered by prednisone, related to her CP and immature brain or was it spontaneous\r\nand unrelated?

Faria Khan has done his M.B.,B.S. from University Of Health Sciences in 2011 at the age of 24. Now she is doing her post graduate residency from Chughtai Lab.\r\nin Histopathology

Primary neuroendocrine tumors of testis are less common accounting for <1% of all testicular neoplasms and even rare when arise\r\nin testicular teratomas. Herein, we present a case of neuroendocrine tumor arising in postpubertal teratoma in 32 year old male\r\nwho presented with complaints of abdominal swelling associated with history of undesended left testis. His serum levels of beta-\r\nHCG, AFP and LDH were slightly elevated. Later, left orchidectomy was performed. Macroscopically, a grey white well circumscribed\r\ntumor of 2.5x2.0x1.8cm within testicular parenchyma is identified. Histological examination of entirely submitted tumor reveals a\r\nneoplasm showing organoid arrangement of round blue cells with salt and pepper chromatin, rosettes formation and occasional\r\nmitosis. Features of mature teratoma were seen in background. No other germ cell component (choriocarcinoma, seminoma, yolk\r\nsac tumor and embryonal carcinoma) was noted. Immunohistochemistry reveal positivity for Synaptophysin and Chromogranin-A\r\nwith Ki-67 index of 3-20% which confirmed a well differentiated neuroendocrine tumor (Grade 2) arising in postpubertal teratoma.\r\nPrognosis of these malignant transformation depend upon stage of tumor, as teratoma with malignant transformation carry excellent\r\nprognosis following radical orchidectomy if confined to testis (Stage 1). Postpubertal teratomas are considered itself malignant with\r\nthe chances of metastasis at time of presentation, so close follow-up is advised so that earliest possible interventions could be done\r\nprior to advanced stage/metastasis for better prognosis and long term survival.

Fatima Rooman did her MBBS from University of Health Sciences in 2012. Currently, she is persuing her post graduate residency from Chughtai Lab in Histopathology.

Squamous cell carcinoma of cervix is the most common gynecological malignancy caused by human papilloma virus (HPV) infection. Squamous cell carcinomas account for about 70% cases of cervical cancers. Invasive cervical cancer is ranked as the third most common cancer worldwide. Extension of cervical squamous cell carcinoma in situ or invasive tumor into the endometrium without myometrial invasion is an extremely rare phenomenon. We present a case of 65 years old female clinically presented with cervical discharge and lower abdominal pain. Clinical diagnosis of pyometra was made followed by total abdominal hysterectomy and bilateral salpingo-opherectomy. Histopathological examination revealed full thickness dysplasia in the lining epithelium of cervix extending superficially to endometrium without any myometrial involvement. No evidence of invasive tumor was seen in entirely examined cervix and endomyometrium. Sections from bilateral adnexae were unremarkable. Hence, the diagnosis of cervical squamous cell carcinoma in situ extending superficially to the endometrium was rendered. This lesion has not yet been included in The International Federation of Gynaecology and Obstetrics staging or in The World Health Organization classification. The prognostic significance and management guidelines for such unusual type of spread of cervical cancer are also not clear. It is hoped that increase in reporting of such rare cases will help in recognition of this as a separate entity with pathogenesis and formulation of management guidelines.

Sameen Afzal did her M.B.,B.S. from University Of Health Sciences in 2013 at the age of 24. Now she is doing her post graduate residency from Chughtai Lab in Histopathology

Mature cystic teratoma (MCT) is the most common type of ovarian germ cell tumor occurring in females of reproductive age. It is typically benign, but rare malignant transformation has been reported in 1-2% of the cases. Among a wide variety of malignancies arising in MCTs, high grade lymphomas are among the least common malignancies. We present a case of a 45 years old female with a unilateral adnexal mass. Gross examination revealed a unilocular cyst with a smooth and intact capsule. The lumen of the cyst was filled with sebaceous material and hair. Except for a 5.0cm Rokitansky nodule, no other nodule or papillary structures were identified. Microscopic examination revealed an array of mature tissues arising from different germ cell layers and foci of diffuse sheets of large atypical lymphoid cells. These were positive for CD-20 immunohistochemical marker, confirming their B lymphoid series cell origin. A final diagnosis of a High Grade B- Cell Non Hodgkin’s Lymphoma arising in an ovarian mature cystic teratoma was made. Such cases have been known to be associated with a very poor prognosis and there are no established criteria for their pre-operative diagnosis. Risk factors for malignant transformation in a MCT are thus analyzed routinely to make a presumptive diagnosis. Some of these factors include; tumor size, post menopausal status and serum tumor markers. These coupled with extensive gross sampling of the tumor specimens and a diligent histopathological examination may aid in an accurate diagnosis of a malignant neoplasm arising in MCTs.

Fatima S did her MBBS from University of Health Sciences 2010. Currently, she is perusing her post graduate residency from Chughtai Lab. in Histopathology.

Schwannomas are benign peripheral nerve tumors, occurring in third to fifth decade of life and presenting as solitary tumor mostly in head and neck region followed by upper and lower extremities. They account for 8% of the tumors of soft tissue and are composed entirely of schwann cells. Various variants of schwanomma have been described as; cellular, plexiform, ancient and psammomatouse. Plexiform schwanomma (PS) is an unusual and rare varient of schwanomma. About 5% of schwannomas grow in plexiform or multinodular pattrern which may or may not be apparent macroscopically. They usually occur in skin and frequently in deep sites. Like classic schwannomas they are encapsulated, but as a group, are more cellular and therefore qualifies also as cellular schwannomas. It is important to be aware of this fact because there is a risk of misinterpreting a lesion as a sarcoma arising in a plexiform neurofibroma. It may occur in patients of neurofibromatosis 2 (NF-2) and schwanomatosis and can easily be confused and mis diagnosed as neurofibromas. We present a case of PS ocuring in a 15 years old male as recurrent index finger mass with no syndromic history. We recieved multiple whitish tissue fragments with grossly nodular cut surface. Histological examination revealed multiple well encapsulated nodules with classic picture of schwannoma having hypercellular (Antoni A) and hypocellular (Antoni B) areas with prominant verocay bodies. S-100 immunohistochemical stain showed diffuse positivity. Surgical excision and tumor removal is the usual mode of treatment of PS. The prognosis is excellent, if the tumor is removed completely without damaging the underlying nerve. Most schwannomas are benign and do not recur when completely excised.

Sihem Darouich, MD, is a Fetopathologist at the University Hospital Habib Bougatfa of Bizerte and Professor at the Department of Histology and Embryology, Faculty of Medicine of Tunis, Tunisia. Over the last several years, she has focused on fetal genetic syndromes, especially syndromic multicystic renal dysplasia and skeletal dysplasias. She is a member of the French Society of Fetopathology (SoFFoet) and of an editorial board of a reputed international journal.

Hypophosphatasia is a rare skeletal dysplasia, related to inactivating mutations in the TNSALP gene encoding the tissue-non-specific alkaline phosphatase. This enzyme deficiency mainly results in disorders of bone and teeth mineralization. The phenotypic spectrum ranges from perinatal lethal to mild form diagnosed in adulthood. We describe the lethal form in three affected fetuses, one female and two males. Antenatal ultrasound detected micromelia and generalized demineralization. Termination of pregnancy was performed at 18, 22 and 25 weeks of amenorrhea. Skeletal radiographs showed irregular ossification in all cases, that was very poor with only few mineralized bones in two cases, and associated with bowing of the long bones and large, irregular metaphyses in one case. Macroscopic examination showed micromelia, bowing of the limbs and a characteristic craniofacial dysmorphism including relative macrocrania, hypertelorism, small nose with anteverted nostrils, long philtrum, thin lips, miroretrognathia and low-set ears. Bilateral tibial or tibio-peroneal spurs were observed in two cases. The histology disclosed the presence of columns of hypertrophic chondrocytes invading the diaphysis. In conclusion, perinatal hypophosphatasia is characterized by severe micromelia and major deficit or complete absence of the bone mineralization. It is often confused with osteogenesis imperfecta on prenatal ultrasound. However, the 3D ultrasound can detect the characteristic bone spurs in the early second trimester and strongly orient the diagnosis towards lethal hypophosphatasia. The diagnosis is confirmed by detailed fetopathological examination including skeletal radiography, macroscopic examination and histological study of longs bones. Genetic counseling can be offered with genetic testing to parents.

Sihem Darouich, MD, is a Fetopathologist at the University Hospital Habib Bougatfa of Bizerte and Professor at the Department of Histology and Embryology, Faculty of Medicine of Tunis, Tunisia. Over the last several years, she has focused on fetal genetic syndromes, especially syndromic multicystic renal dysplasia and skeletal dysplasias. She is a member of the French Society of Fetopathology (SoFFoet) and of an editorial board of a reputed international journal.

Blomstrand chondrodysplasia is a very rare lethal skeletal dysplasia due to loss-of-function mutations in the gene encoding the type 1 parathyroid hormone receptor (PTHr). It is associated with resistance to the PTH that results in acceleration of endochondral ossification and bone remodeling deficiency. Our aim is to discuss the clinico-pathological characteristics of Blomstrand chondrodysplasia in a 21-week male fetus and the usefulness of the fetopathological examination in the diagnosis of this condition. Antenatal ultrasound showed severe tetramicromelia and hydrops fetalis, leading to the termination of pregnancy. Postmortem radiographs showed increased bone density, accelerated bone maturation (presence of points of ossification in pubis and calcaneum), irregular short ribs, short tubular bones with wide metaphyses and ossification of the hyoid bone and laryngeal cartilages. Macroscopic examination confirmed the fetal hydrops and the extreme tetramicromelia, and demonstrated characteristic craniofacial dysmorphism including mild exophthalmos, hypoplastic nose, protrusion of the tongue, micrognathia, low-set and badly-hemmed ears. Besides, short and wide neck, markedly narrow thorax, prominent abdomen, broad and short hands and feet, and pulmonary hypoplasia were also noted. On microscopy, the hyaline cartilage exhibited a compact and dense appearance and ectopic points of ossification without obvious primary ossification center. Additionally, the growth plate was often completely absent with presence of few columns of hypertrophic chondrocytes, lack of a readily identifiable proliferative zone, very irregular ossification line, thick layers of endochondral bone matrix and decreased size of the marrow spaces.

Sihem Darouich, MD, is a Fetopathologist at the University Hospital Habib Bougatfa of Bizerte and Professor at the Department of Histology and Embryology, Faculty of Medicine of Tunis, Tunisia. Over the last several years, she has focused on fetal genetic syndromes, especially syndromic multicystic renal dysplasia and skeletal dysplasias. She is a member of the French Society of Fetopathology (SoFFoet) and of an editorial board of a reputed international journal.

Type III lissencephaly is reported as a lethal familial disorder (OMIM 601160). It is a syndromic entity that comprises intrauterine growth retardation (IUGR), fetal akinesia deformation sequence (FADS), severe microcephaly, agyria, spino-pontocerebellar atrophy and diffuse neurodegeneration. We report a 22-week male fetus who achieved typical features of type III lissencephaly, which led to termination of pregnancy. Ultrasonography showed IUGR, polyhydramnios, microcephaly, hydrocephaly, cerebellar hypoplasia and limb deformities. The fetus was born to nonconsanguinous parents with a healthy child. Array CGH didn’t detect genomic imbalances. Detailed fetopathological examination was carried out after parental consent. It confirmed the IUGR and revealed multiple anomalies including craniofacial dysmorphism, short and wide neck, FADS, genital hypoplasia, severe four-limb amyoplasia, thoracic scoliosis, pulmonary hypoplasia, cardiac hypotrophy, adrenal hypoplasia, common mesentery and single umbilical artery. The neuropathological examination showed external hydrocephalus with enlarged subarachnoid spaces, hydranencephaly, severe spino-pontocerebellar hypoplasia and corpus callosum agenesis. Histology revealed a decrease of the testicular Leydig cells and confirmed the clinical impression of neurogenic muscular atrophy. It disclosed a diffuse neurodegeneration involving the grey and white matter as well as atrophy of the corticospinal tracts and vermian agenesis. Additionally, degeneration of motor neurons in the spinal anterior horns was noted. Microcalcifications were found in the cerebal hemispheres and brainstem. In conclusion, the type III lissencephaly is a central nervous system neurodegenerative disease with early prenatal onset. It’s a very challenging condition because its molecular basis is not yet been elucidated. Thus, an adequate genetic counselling cannot be given to the parents.