Pleuropulmonary blastoma masquerading as pneumothorax in a patient with a ventricular septal defect.

Pleuropulmonary blastoma is a rare pediatric primary lung tumor. We report a case of a child with Down syndrome and a large ventricular septal defect presenting with pleuropulmonary blastoma initially misdiagnosed as spontaneous pneumothorax. Following tube thoracostomy drainage of the pneumothorax, the child underwent surgical closure of the ventricular septal defect. However, the postoperative period was complicated by recurrent left pleural collection requiring prolonged intercostal tube drainage and two thoracotomies to evacuate the necrotic pleural material. The biopsy of the necrotic material was suggestive of type III pleuropulmonary blastoma. In view of the high propensity of metastasis associated with this variant of a tumor, the patient was started on chemotherapy. This case report highlights the possibility of pleuropulmonary blastoma presenting as pneumothorax and emphasizes the need to consider the etiology, before intervening in a child presenting with spontaneous pneumothorax.

Complete Tracheal Ring Deformity, Recurrent Pneumothoraces and Pleuropulmonary Blastoma in a Child: Coincidence or Common Genetic Cause?

Complete tracheal ring deformity (CTRD) is a rare abnormality of unknown etiology characterized by circumferentially continuous cartilaginous tracheal rings leading to variable degrees of tracheal stenosis with or without additional heart and lung malformations. Pleuropulmonary blastomas (PPB) are rare malignant mesenchymal tumors, which occur almost exclusively in young children. Pathogenic germline DICER1 variants are associated with PPB but also with other tumors like rhabdomyosarcoma or syndromic diseases like GLOW (Global developmental delay, lung cysts, overgrowth and Wilms tumor) syndrome. Here, we report a case with CTRD and recurrent pneumothoraces who additionally developed PPB on the genetic background of a pathogenic DICER1 variant.

DICER1-associated hepatic cystic neoplasm with pleuropulmonary blastoma-like features: a novel clinicopathologic diagnosis.

This report documents a unique multicystic neoplasm of the liver in an 8-month-old boy with a heterozygous germline pathogenic DICER1 variant. This neoplasm, initially considered most likely a mesenchymal hamartoma based on imaging, demonstrated the characteristic histologic pattern of embryonal rhabdomyosarcoma residing in the subepithelial or cambium layer-like zone of the epithelial-lined cysts. Thus, although the differential diagnosis includes mesenchymal hamartoma, a young child with a multicystic mass lesion in the liver, lung, or kidney should both raise the possibility of a germline pathogenic DICER1 variant and also not be mistaken for one of the other hepatic neoplasms of childhood.

DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma.

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.

Pulmonary Blastoma in an Adult Presenting With Hemoptysis and Hemothorax.

Pulmonary blastoma is a rare, aggressive neoplasm accounting for less than 1% of lung cancers in adults. Reported is a case of pulmonary blastoma in an adult with the unusual presentation of hemoptysis followed by large hemothorax. The patient received a lobectomy. Pathologic examination showed clear resection margins without nodal involvement. However, the patient developed recurrence 4 months postoperatively and died shortly thereafter. The clinical characteristics of pulmonary blastoma are discussed.

A 34-Year-Old Pregnant Woman With Cough, Chest Pain, and a Left Upper Lobe Mass.

A 34-year-old white woman who was 30 weeks' pregnant initially presented to her primary care physician with a cough for which she was given antibiotics, but she had persistent symptoms. These were followed by chest pain, as a result of which she was referred to our department. She had a past medical history of hypertension, and currently was in her sixth pregnancy, with no reported complications in the previous pregnancies. Review of systems was otherwise negative. She had a three-pack-year smoking history, but denied smoking during her current pregnancy.

A Rare Case of Childhood Stiff Person Syndrome Associated With Pleuropulmonary Blastoma.

INTRODUCTION: Stiff person syndrome is a rare autoimmune, neurological disorder characterized by progressive rigidity and episodic painful spasms, predominantly affecting the proximal limbs and axial muscles, and leading to progressive disability. We report the case of a child who developed symptoms compatible with stiff person syndrome during treatment for pleuropulmonary blastoma. PATIENT DESCRIPTION: A 3-year, 5-month-old girl was admitted for gradually worsening postural tremor, painful spasms, and generalized stiffness. Since the age of 3 years, she had been on adjuvant chemotherapy for pleuropulmonary blastoma before surgical resection. Brain magnetic resonance imaging and electroencephalographic findings were normal. Although serologic tests for autoimmune disease, including paraneoplastic antibodies and antiglutamic acid decarboxylase antibodies, were unremarkable, her findings were attributed to a paraneoplastic syndrome based on her clinical features and medical history. However, following the planned pulmonary lobectomy, her symptoms were paradoxically aggravated, with continuous motor unit potential at rest on electromyography, which occurs in stiff person syndrome. She gradually improved during postadjuvant chemotherapy with simultaneous immunotherapy including intravenous immunoglobulins and methylprednisolone, and she had recovered completely when evaluated at the 22-month follow-up visit after completion of her treatment for pleuropulmonary blastoma. CONCLUSION: We present the first documented child with stiff person syndrome associated with pleuropulmonary blastoma. The marked clinical improvement following chemotherapy for pleuropulmonary blastoma was yet more proof of the pleuropulmonary blastoma-related stiff person syndrome. In children with a malignancy and stiff person syndrome, a paraneoplastic syndrome should be considered and the treatment for the malignancy must be undertaken.

Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry.

BACKGROUND: Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases. METHODS: Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing. RESULTS: There were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P = .0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P = .0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome. CONCLUSIONS: Cystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes.

Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder.

Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition disorder. Original pathologic materials from individuals with a PPB, PPB-associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1. Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6-21 years). NCMH developed 4.5-13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0-16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n = 2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations. Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms.

Type III pleuropulmonary blastoma in a 7-month-old female baby with impending respiratory failure: a case report.

INTRODUCTION: Pleuropulmonary blastoma is a very rare, aggressive, embryonal pulmonary neoplasm which mostly affects children under the age of 5. According to the histopathological features, three subtypes of pleuropulmonary blastoma have been recognized: type I (purely cystic), type II (grossly visible cystic and solid elements) and type III (purely solid). Characteristics of type I and type II blastoma allow an earlier diagnosis compared with type III. Here we present a case report of an unusual presentation of type III pleuropulmonary blastoma. CASE PRESENTATION: We describe the case of a 7-month-old female baby of Italian mother and Kurdish father who was diagnosed with type III pleuropulmonary blastoma, which entirely occupied her right hemithorax. CONCLUSIONS: The reported case is an unusual presentation because type III pleuropulmonary blastoma typically occurs in older children. The complete re-expansion of her residual, previously totally compressed, right lung observed immediately after the resection of the lesion suggests an atypical rapid growth of this embryonal tumor in the late phase of gestation or after delivery. This case report suggests that, in addition to other childhood tumors, type III pleuropulmonary blastoma should be included in the differential diagnosis of solid nonhomogeneous thoracic large masses, compressing the mediastinal and chest wall structures in infants. This is an original case report of interest for several specialities such us pediatrics, radiology, surgery and oncology.

Discoid lupus and pulmonary blastoma in an elderly patient.

Discoid lupus is an autosomal disease that has not been found to predispose to cancer. Pulmonary blastoma is a rare primary lung tumor with a poor prognosis, which commonly presents at a younger age than non-small-cell lung carcinoma. We report a rare case of pulmonary blastoma in a 62-year-old man with discoid lupus who presented with chronic cough and pleuritic pain. The 5.3-cm tumor was located in the left upper lobe, invaded the visceral pleura, and adhered to the parietal pleura. The patient underwent a left upper lobectomy and chest wall excision, with adjuvant chemotherapy and radiotherapy.

An unusual manifestation of a rare pleuropulmonary blastoma presenting with spinal cord compression and its neurosurgical implications.

Pleuropulmonary blastomas (PPB) are rare and biologically aggressive paediatric tumours. Although central nervous system metastatic dissemination is a recognised complication of PPB, to our knowledge, spinal cord compression has been described only in six patients. We report a 5-year-old boy with a diagnosis of recurrent type III PPB that was initially thought to be an empyema, who developed features of thoracic spinal cord compression secondary to local tumour infiltration. Although PPB demonstrate significant biologically aggressive behaviour, aggressive surgical resections together with adjuvant chemotherapy can help limit disease progression without impacting on the quality of life. Spinal metastatic disease should also be treated vigorously. In this paper we discuss the treatment strategies available in the management of PPB.

Follicular thyroid carcinoma arising after hematopoietic stem cell transplantation in a child with pleuropulmonary blastoma.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm that is associated with other dysplastic or neoplastic conditions. The prognosis, especially of type II (cystic and solid) and type III (solid) PPB, is poor. High-dose chemotherapy (HDC) and hematopoietic stem cell transplantation (HSCT) have been attempted to improve survival rates. We report the development of follicular thyroid carcinoma in a girl who was treated at a young age for PPB. SUMMARY: A 23-month-old girl was evaluated for a clinical diagnosis of pneumonia and was found to have a mass in the left lung that grew rapidly. It was removed and diagnosed as a PPB. At the age of two, she was referred to our hospital for further treatment. She received adjuvant chemotherapy for 6 months but developed a recurred mass in her back at 4.3 years of age. After removal of the mass, she was given a salvage chemotherapy followed by HDC and HSCT but not radiation treatment between 4.4 and 4.9 years of age. At the age of seven, after 2 years without treatment, she presented with multiple thyroid nodules in both lobes that steadily grew over the next 2 years. At the age of nine, she underwent total thyroidectomy, which revealed an invasive follicular carcinoma. She remained without clinical evidence of thyroid cancer for one year since the surgery. Radiation therapy was not administered because of the concerns of causing another malignancy. A literature search combined with the present case indicated that, of the five living patients who had been treated with HDC and HSCT, three developed a follicular thyroid carcinoma. CONCLUSIONS: The high prevalence (3/5, 60%) of follicular thyroid carcinoma in patients with PPB who were treated with HDC and HSCT is striking. This suggests that, in patients with PPB, either HDC or HSCT contributes to the development of thyroid cancer. Clinicians should be advised of the high risk of thyroid carcinoma occurrence when HDC and HSCT are being contemplated in children with PPB.

Translocation t(12;17)(q24.1;q21) as the sole anomaly in a nasal chondromesenchymal hamartoma arising in a patient with pleuropulmonary blastoma.

The identification of recurrent chromosomal abnormalities in benign and malignant mesenchymal neoplasms has provided important pathogenetic insight as well as powerful diagnostic adjuncts. Nasal chondromesenchymal hamartoma (NCMH), an extremely rare benign tumor arising in the sinonasal tract of infants and children, has not been previously subjected to cytogenetic analysis. Histopathologically composed of mixed mesenchymal elements, NCMH exhibits a relatively wide differential diagnosis to include chondromyxoid fibroma, chondroblastoma, aneurysmal bone cyst, fibrous dysplasia, and osteochondromyxoma. An interesting association with pleuropulmonary blastoma has been reported in a small subset of NCMH patients. In the current study, cytogenetic analysis of a NCMH arising in an 11-year-old boy with a past medical history of pleuropulmonary blastoma revealed a novel 12;17 translocation, t(12;17)(q24.1;q21), as the sole anomaly.

Classic pulmonary blastoma: a subtype of biphasic pulmonary blastoma.

We report a rare case of classic pulmonary blastema (CPB) without recurrence for 3 years after the operation. A 70-year-old man presented with cough and sputum for a month. Chest computed tomography (CT) showed a 5cm-sized mass in the right middle lobe. Bronchoscopic examination was performed, and the mass was suspected as adenocarcinoma of the lung. Right middle lobectomy and lymph node dissection were performed. The pathologic histology diagnosis was classic pulmonary blastoma, a subtype of biphasic pulmonary blastoma.

Pleuropulmonary blastoma as characteristic cause of pneumothorax.

BACKGROUND: Pleuropulmonary blastoma (PPB) is the most common lung neoplasms in childhood. Usually presents as recurrent respiratory infections and in some cases as pneumothorax. CASE REPORT: We report the case of a 2-year-old patient that was diagnosed with PPB, that first manifested as recurrent pneumothorax. Three chest computed tomography were necessary for the diagnosis. The first 2 tomographies showed no abnormalities suggestive of malignancy. The patient had a family history of both PPB and leukemia. Three years and a half after completion of treatment, the patient is in complete remission. CONCLUSIONS: PPB is an uncommon disease but is the most common pulmonary neoplasms in childhood. We must suspect it in patients with a suggestive family history and recurrent pneumothorax in the same location.