Calretinin Staining in Anorectal Line Biopsies Accurately Distinguished Hirschsprung Disease in a Retrospective Study.

INTRODUCTION: The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. METHODS: Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis. RESULTS: Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm. CONCLUSIONS: Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

Congenital granular cell epulis: 24 new cases with more differences than similarities to granular cell tumor.

Congenital granular cell epulis (CGCE) is a rare tumor of gingiva that is exclusive to newborns, has marked female predominance, and is rarely associated with other abnormalities. Although benign in behavior, CGCE can be lethal by obstruction of respiration and/or deglutition and can require a multidisciplinary team of specialist at birth for survival of an otherwise normal infant. Histologically, CGCE resembles granular cell tumor (GCT), but unlike GCT, which is Schwannian-derived, derivation of CGCE remains an enigma, largely because of its low prevalence. This study presents 24 new cases of CGCE, the largest series since the original description 150 years ago and permits detailed study of homogeneity of cases diagnosed as CGCE as well as detailed comparisons of CGCE with GCT by clinical, morphological, immunohistochemical, and ultrastructural studies. The data show homogeneity within the CGCE cases, more differences than similarities between CGCE and GCT, and no immunohistochemical staining for common placental proteins/hormones in CGCE. The findings support a primitive mesenchymal cell origin, and a progressive degenerative process in CGCE, rather than neoplasia. Prenatal detection of this lesion is important to facilitate adequate preparations for support of these infants during labor and delivery.

Desmoplastic Small Round Cell Tumor of the Kidney: Report of a Case, Literature Review, and Comprehensive Discussion of the Distinctive Morphologic, Immunohistochemical, and Molecular Features in the Differential Diagnosis of Small Round Cell Tumors Affecting the Kidney.

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive neoplasm typically presenting with widespread involvement of the abdominopelvic peritoneum of adolescent males, usually without organ-based primary. Although it is believed to originate from the serous (mainly peritoneal) membranes, intracranial, sinonasal, intraosseous, and other soft tissue sites are also documented. A chromosomal translocation t(11:22)(p13;q12) signature that fuses EWSR1 and WT1 genes results in the production of a chimeric protein with transcriptional regulatory activity that drives oncogenesis. Integration of clinical, morphologic, immunohistochemical, and genetic data is necessary to arrive at the correct diagnosis, especially when the tumor arises in an atypical site. A 15-year-old male presented with hematuria and was found to have a large renal tumor associated with adrenal, liver, lung, and bone metastases. Histopathologic and immunophenotypic features were distinctive for DSRCT. This diagnosis was confirmed by means of fluorescence in situ hybridization and cytogenetic analysis, which documented the pathognomonic t(11;22) translocation, and by reverse transcription polymerase chain reaction on snap-frozen tissue, which revealed the EWSR1/WT1-specific chimeric transcript. Despite high-dose chemotherapy and radiation therapy targeted to a single T11 vertebral metastasis, the disease progressed, and the patient died 4 years after the diagnosis. A search of electronic databases for DSRCT yielded 16 cases of well-documented renal primaries out of around 1570 cases from all sites gathered from the global literature. Desmoplastic small round blue cell tumor and other primary renal tumors considered in the differential diagnosis with DSRCT are discussed.

Metastatic Basal Cell Carcinoma of the Skin: A Comprehensive Literature Review, Including Advances in Molecular Therapeutics.

Basal cell carcinoma (BCC) of the skin is the most common type of malignant human tumor. In Europe, the incidence of BCC ranges from 44.6 to 128 cases per 100,000 inhabitants annually, whereas in the United States, the yearly incidence rate ranges between 500 and 1500. The global incidence has been calculated to be as high as 10 million cases of BCC per year. There are 2 main clinical patterns of BCC-the familial BCC in basal cell nevus syndrome and sporadic BCC. The etiology of cutaneous BCC is usually the result of the interaction between solar ultraviolet radiation and genetic factors. Somatic or germline mutations in the effector components of the hedgehog signaling pathway (ie, PTCH1, PTCH2, SMO or SUFU genes) are responsible for ∼90% of the cases of both sporadic and familial BCC, all causing a constitutive activation of the hedgehog pathway. Cutaneous BCC very rarely metastasizes, and diagnosis in metastatic sites can be very difficult. Metastatic BCC has weakly effective therapeutic options with a poor prognosis until few years ago. In 2012, small-molecule therapies, involving inactivation of the hedgehog signaling pathway, and capable of reducing tumor growth and progression have been introduced into clinical practice for advanced (locally advanced or metastatic) BCC. We performed a comprehensive literature review on metastatic BCC and found at least 915 cases reported to date. In addition, we extensively discussed the differential diagnosis of metastatic BCC, and outlined the advances in clinical therapeutics involving these small molecules.

Phosphaturic Mesenchymal Tumor of Soft Tissue of the Foot: Report of a Case With Review of the Literature.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm that ectopically secretes fibroblast growth factor 23, a bone cell-derived protein that regulates phosphate homeostasis. The overproduction of fibroblast growth factor 23 causes a paraneoplastic syndrome characterized by hyperphosphaturia, hypophosphatemia, hypovitaminosis D, and vitamin D refractory rickets/osteomalacia, effects that disappear with tumor removal. The PMT may occur in several anatomic regions, mainly in the limbs, usually involving both soft tissue and bone. Acral locations occur in 10% to 15% of the cases, mostly in the feet, with 95 cases reported in this anatomic region to date. We report a case of a PMT in a young adult male who presented in 2007 with the classic constellation of signs and symptoms. A small soft-tissue tumor was detected in his right heel, 3 years after exhaustively seeking for it by various imaging techniques performed at different institutions. Before the tumor was detected, attempts to manage this patient's osteomalacia with phosphate and vitamin D (both calcitriol and ergocalciferol) supplementation were unsuccessful. Following surgical resection, the patient experienced prompt correction of the phosphaturia and gradual reconstitution of his bone mineralization. The pathologic diagnosis was (benign) PMT, mixed connective tissue type. In 2019, 12 years after resection, the patient is asymptomatic, and his bone mineral homeostasis has been restored.

Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene.

Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient's peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as "hemangioblastoma-only VHLD", 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case. In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but - for the first time - also in 3 sporadic ones, two of which with novel mutations.

Solitary Fibrous Tumors in Pediatric Patients: A Rare and Potentially Overdiagnosed Neoplasm, Confirmed by STAT6 Immunohistochemistry.

Pathological diagnosis of solitary fibrous tumor (SFT) in the pediatric population is challenging, as it occurs uncommonly in this age-group and resembles other spindle cell neoplasms. SFT contains a NAB2-STAT6 fusion gene, which can be reliably detected using STAT6 immunohistochemistry. Positive staining is highly sensitive and specific. We sought to investigate the utility of STAT6 immunohistochemistry, to show how commonly SFT was historically recognized at 3 academic pediatric institutions, to reclassify them when appropriate, and to demonstrate features of major mimics of SFT. Our series included cases with a previous diagnosis of SFT or for which SFT was among key considerations, from 3 major academic pediatric hospitals seen over the past 30 years. Of 18 tumors identified, only 3 tumors from 2 patients demonstrated positive STAT6 staining as well as the typical histology and immunophenotype seen in SFT. The remaining 15 tumors were reclassified based on morphology, additional immunohistochemistry and fluorescence in situ hybridization as desmoid-type fibromatosis (3 tumors), nerve sheath/neural tumors (3 tumors), low-grade fibromyxoid sarcoma, medallion-like dermal fibroma, poorly differentiated Sertoli cell tumor, nodular/proliferative fasciitis, calcifying fibrous tumor, aneurysmal bone cyst of soft tissue, STAT6-negative SFT with adipocytic differentiation, undifferentiated small round blue cell tumor, and scar (1 tumor each). Our study confirms that SFT is rare in the pediatric population and that it is potentially overdiagnosed. STAT6 immunohistochemistry is recommended to confirm the diagnosis of SFT in the pediatric population.

Extraneuraxial Hemangioblastoma: Clinicopathologic Features and Review of the Literature.

Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD). The world literature on the topic of extraneuraxial hemangioblastomas has been comprehensively reviewed with ∼200 cases reported to date: up to 140 paraneuraxial, mostly of proximal spinal nerve roots, and 65 peripheral, 15 of soft tissue, 6 peripheral nerve, 5 bone, and 39 of internal viscera, including 26 renal and 13 nonrenal. A handful of possible yet uncertain cases from older literature are not included in this review. The clinicopathologic features of extraneuraxial hemangioblastoma are selectively presented by anatomic site of origin, and the differential diagnosis is emphasized in these subsets. Reference is made also to 10 of the authors' personal cases of extraneuraxial hemangioblastomas, which include 4 paraneuraxial and 6 peripheral (2 soft tissue hemangioblastoma and 4 renal).

Selected case from the Arkadi M. Rywlin International Pathology Slide Club: carcinoma of the transverse colon in a young girl.

We report a case of a 14-year-old female with primary adenocarcinoma of the transverse colon. She was hospitalized after presenting with abdominal pain and signs of intestinal obstruction. There was no health antecedent or family history of neoplasia. Physical examination revealed a distended abdomen. Tenderness was elicited to palpation of the right lower quadrant. Magnetic resonance imaging of the abdomen revealed obstructive signs, with a constricting lesion in the mid-transverse colon of probable neoplastic nature. Laparoscopic segmental resection of the colon was followed by standard right hemicolectomy. A circumferential mid-transverse tumor was diagnosed as primary colorectal carcinoma (CRC) of signet-ring cell type, AJCC stage IIIC, Dukes' C stage. On the basis of immunohistochemistry and clinical data, hereditary nonpolyposis and hamartomatous colorectal cancer syndromes were excluded. Involvement of either the p53, BRAF, or K-RAS genes was ruled out by immunohistochemistry profiling and genetic testing. The neoplasm was categorized as sporadic. The possibility of activation of the Wnt signaling pathway was suspected, because of a defective turnover of the ß-catenin protein. Postoperatively, the patient was treated with both systemic and intra-abdominal adjuvant chemotherapy, including oxaliplatin. Between 18 and 24 months after diagnosis, intra-abdominal tumor recurrences were detected. The patient underwent bilateral oophorectomies for Krukenberg tumors and received salvage chemotherapy. Recently, additional recurrent metastatic retroperitoneal disease caused hydronephrosis. The retroperitoneal mass was debulked and a ureteric stent was placed. At the time of this writing, 43 months after diagnosis, the patient is receiving FOLFOX chemotherapy combined with panitumumab. CRC of childhood is exceedingly rare, generally develops in the setting of unrecognized genetic predisposing factors to cancer, presents with advanced disease, is high grade, and tends to have dismal prognosis.

Selected case from the Arkadi M. Rywlin International Pathology Slide Series: Asymmetric, segmental glomerulocystic kidney in an infant with tuberous sclerosis complex.

A Hispanic newborn male, the product of nonconsanguineous parents, exhibited major and minor signs of tuberous sclerosis complex (TSC). MRI of the abdomen disclosed a discrete unilateral, cystic, right upper pole renal mass that prompted a nephrectomy. Histologic examination showed a polycystic renal mass that involved all segments of the nephron, with a preponderantly glomerulocystic pattern. The cysts were rounded, uniform, and small, most measuring 2 to 3 mm in diameter. The lining of the cysts was hyperplastic, made up of tall epithelial cells with eosinophilic granular cytoplasm and large nuclei, and focally formed mounds and papillary tufts. DNA analysis detected a constitutional deletion of exon 1 in the TSC2 gene on chromosome 16p13.3. Cystogenesis in TSC2 is manifested because of alteration or dysfunction of the primary cilium, where polycystin, the gene product of PKD1 gene, is localized. Renal cysts are often seen in TSC, varying in number from a few to innumerable, involving all segments of the nephron, including Bowman spaces, and are currently considered as one of the minor diagnostic features. A glomerulocystic pattern is a rare form of kidney involvement in TSC that aptly describes the innumerable cystically dilated Bowman spaces. Glomerulocystic kidney associated with the aforementioned hyperplastic epithelial lining (TSC epithelium) is sufficiently characteristic that could conceivably serve as a major TSC feature in the future.

A 14-year old girl with reversible hypoglycemic episodes: the role of ASVS.

We present the case of a 14-year-old female who experienced several episodes of reversible altered mental status triggered by hypoglycemia. Following endocrine investigation, she was diagnosed with insulinoma. Insulinoma, a rare, differentiated, and functioning neuroendocrine tumor of the pancreas overproduces insulin, thus leading to hypoglycemic episodes. Conventional imaging failed to detect the lesion; therefore, arterial calcium stimulation with venous sampling (ASVS) was used for preoperative localization. The patient recovered without complications after surgical enucleation of the tumor. The ASVS is a useful method for localizing insulinomas when conventional imaging techniques fail, and can help reduce morbidities associated with surgical excision.

Selected case from the Arkadi M. Rywlin International Pathology Slide Series: Mitochondrial myopathy presenting with chronic progressive external ophthalmoplegia (CPEO): a case report.

A 43-year-old female patient diagnosed with chronic progressive external ophthalmoplegia (CPEO) because of mitochondrial myopathy documented by muscle biopsy is presented. The chief complaints were represented by blepharoptosis and ophthalmoplegia. The muscle biopsy was evaluated by histology, using the appropriate histochemical and histoenzimological stains. Ragged red fibers with Gomori trichrome stain were seen, which showed cytochrome c oxydase deficiency and abnormal succinate dehydrogenase staining in around 20% of muscle fibres. Electron microscopy was also performed which demonstrated abnormal, hyperplastic, pleomorphic, and hypertrophic mitochondria, characterized by paracrystalline inclusions arranged in parallel rows ("parking-lot" inclusions), consisting of rectangular arrays of mitochondrial membranes in a linear or grid-like pattern. In conclusion, mitochondrial myopathy was definitely diagnosed. Although molecular analysis, which was subsequently carried out, failed to reveal mutations in the mitochondrial DNA or in selected nuclear genes, the pathologic diagnosis was not changed. The differential diagnosis of CPEO with other forms of ocular myopathies as well as the possible association of CPEO with systemic syndromes is discussed. Ophtalmologists and medical internists should always suspect CPEO when dealing with patients affected by ocular myopathy, either in its pure form or in association with other myopathic or systemic signs.

Selected case from the Arkadi M. Rywlin international pathology slide series: lymphangiomatosis of the spleen associated with ipsilateral abdominopelvic and lower extremity venolymphatic malformations: a case report and review of the literature.

Herein, we report a 26-year-old patient with lymphangiomatosis of the spleen associated with multiple lymphatic and venous malformations. This patient underwent excision of a large lymphatic malformation of the left abdominal wall during childhood. A venous malformation of her left lower limb was excised during adolescence. Additional lymphatic malformations were found in the soft tissue of her left thigh at the age of 20. During hospitalization for a huge vulvar hemangioma at the age of 26, she was incidentally found to have asymptomatic splenomegaly, for which she underwent splenectomy. Examination of the spleen revealed diffuse involvement by a lymphatic anomaly predominantly forming small cystic spaces. Lymphangiomatosis of the spleen is rare and is classically separated into an isolated or pure form and a generalized form when it is associated with involvement of other viscera and/or multiple soft-tissue planes. This patient was affected by a borderline form of splenic lymphangiomatosis with limited somatic involvement of the superficial soft tissues and blood vessels. Notably, all the additional vascular malformations in this patient were left sided, and at this time there was no additional involvement of internal organ. No hereditary or known syndrome was identified.

Selected case from the Arkadi M. Rywlin International Pathology Slide Series: Leiomyomatosis peritonealis disseminata: report of 3 cases with extensive review of the literature.

We present the clinicopathologic features of 3 cases of leiomyomatosis peritonealis disseminata (LPD). The patients were 33, 34, and 41 years old at the time of diagnoses. The 3 women had undergone laparoscopic removal of multiple uterine leiomyomas between 1 and 6 years before the diagnoses of LPD. Laparoscopic uterine leiomyomectomies were performed on 3 occasions in patient 1, and once in patients 2 and 3 by the time a diagnosis of LPD was made. In patients 2 and 3, one of the multiple uterine leiomyomas had been qualified as mitotically active. Patients 1 and 2 received hormonal treatment before LPD was diagnosed. Malignancy was clinically and/or pathologically suspected in all the 3 cases. Patients 1 and 2 were managed conservatively. Patient 3 underwent radical hysterectomy with bilateral adnexectomy and omentectomy. Patients 1 and 2 belong to a rare subset of LPD that have fewer tumor nodules larger (5 to 10 cm) than typically seen. Patient 3 was classic in that she exhibited innumerable nodules measuring between a few millimeters and 1.5 cm, intraoperatively mimicking peritoneal carcinomatosis. Histopathologically, patients 1 and 2 were diagnosed as pure LPD, whereas patient 3 was diagnosed as LPD associated with endometriosis (adenomyosis type). Patients 1 and 3 had incipient foci of leiomyomatous changes in the blood vessel walls, at the site of the LPD tumors, supporting the hypothesis that these are de novo lesions arising locally and not migrated or disseminated from the previously excised or concurrent uterine smooth muscle tumors, usually seen in this context. Conceivably, laparoscopic leiomyomectomy with morcellation may play a role in the pathogenesis of this rare condition, at least in hormonally susceptible patients. Alternatively, LPD may derive from metaplastic submesothelial cells, a condition analogous to gliomatosis peritonei.

Epilepsy surgery for early infantile epileptic encephalopathy (ohtahara syndrome).

Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.

Solitary fibrous tumor of the central nervous system: a 15-year literature survey of 220 cases (August 1996-July 2011).

We reviewed the world literature on solitary fibrous tumors of the central nervous system from August 1996 to July 2011, focusing on both clinicopathological features and diagnostic findings. The anatomical distribution of the 220 cases reported so far reveals that most are intracranial and just over one-fifth are intraspinal. In decreasing frequency, intracranial tumors involve the supratentorial and infratentorial compartments, the pontocerebellar angle, the sellar and parasellar regions, and the cranial nerves. Intraspinal tumors are mainly located in the thoracic and cervical segments. Although most solitary fibrous tumors of the central nervous system are dural based, a small subset presents as subpial, intraparenchymal, intraventricular, or as tumors involving the nerve rootlets with no dural connection. Preoperative imaging and intraoperative findings suggest meningioma, schwannoma or neurofibroma, hemangiopericytoma, or pituitary tumors. Immunohistochemistry is critical to establish a definitive histopathological diagnosis. Vimentin, CD34, BCL2, and CD99 are the most consistently positive markers. The usual histologic type generally behaves in a benign manner if complete removal is achieved. Recurrence is anticipated when resection is subtotal or when the tumor exhibits atypical histology. The proliferative index as assessed by MIB1 labeling is of prognostic significance. Occasionally, tumors featuring conventional morphology may recur, perhaps because of minimal residual disease left behind during surgical extirpation. Rare extracranial metastases and tumor-related deaths are on record. Surgery is the treatment of choice. Stereotactic and external beam radiation therapy may be indicated for postsurgical tumor remnants and for unresectable recurrences. Long-term active surveillance of the patients is mandatory.

Erythroblastic sarcoma presenting as bilateral ovarian masses in an infant with pure erythroid leukemia.

Pure erythroid leukemia is a rare subtype of acute erythroid leukemia that is characterized by a predominant erythroid population, and erythroblastic sarcoma has not yet been described in the English literature. Here, we report a first case of erythroblastic sarcoma that presented as bilateral ovarian masses in a 3 ½-month-old infant girl with pure erythroid leukemia. Bone marrow aspirate and biopsy showed that the marrow was completely replaced by large-sized blasts consistent with erythroblasts. Immunophenotypically, both the tumor cells from the ovarian mass and bone marrow blasts were positive for CD117, glycophorin A, and hemoglobin A, demonstrating erythroid differentiation. Reverse transcriptase polymerase chain reaction showed that the tumor cells from ovarian mass expressed hemoglobin F and α1 spectrin, confirming their erythroid lineage. Conventional karyotype of the bone marrow aspirates revealed del(6)(q23q25) and trisomy 7 in all 21 cells examined. Fluorescence in situ hybridization of the ovarian mass demonstrated loss of c-myeloblastosis viral oncogene (C-MYB) at 6q23 locus in 41% of the cells, and deletion of chromosome 7 and 7q in 37% and 66% of cells, respectively. Taken together, we showed, for the first time, that pure erythroid leukemia presented as a myeloid sarcoma in the form of ovarian masses.

Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma--a report from the International Pleuropulmonary Blastoma Registry.

BACKGROUND AND AIMS: Ciliary body medulloepithelioma (CBME) is a rare embryonal ocular tumour of children under age 10 years. Pleuropulmonary blastoma (PPB) is a rare embryonal lung tumour in young children and the sentinel disease of the PPB Family Tumour and Dysplasia Syndrome, a distinctive predisposition leading to unusual dysontogenetic-dysplastic and neoplastic conditions in PPB patients and their relatives. Germline mutations of DICER1 gene, a key regulator of gene silencing, underlie this syndrome. CBME occurs with PPB. The authors' aim was to identify CBME cases associated with PPB. METHODS: The authors evaluated International PPB Registry and literature PPB cases for CBME, including review of pathologic specimens. RESULTS: Four CBME were observed among 550-600 PPB cases; three in patients and one in a parent. One CBME was clinically diagnosed; three were confirmed pathologically (one benign teratoid CBME; one benign non-teratoid CBME; one case, details not available). CONCLUSIONS: These observations suggest that CBME is a manifestation of the tumour predisposition associated with PPB. Paediatric oncologists and ophthalmologists should be aware that CBME can occur in PPB patients or their relatives and that CBME may indicate a hereditable tumour predisposition for a child or family.