Breast cancer management in a case of hemihypertrophy/lymphedema.

Breast cancer can occur in women affected by congenital disorders because of its very high incidence. The circumstances of the underlying disease may affect the treatment plan for the cancer. In our case, breast cancer occurred in a 43-year-old woman with congenital hemihypertrophy and lymphedematous features of the overgrowth. These conditions are described in the article while questions about the best practice for the cancer surgery are mentioned.

Commonest overgrowth syndromes.

Overgrowth syndromes, although rare, are diagnosed more frequently lately. Major progress, such as the identification of genetic causes, has recently enhanced the delineation of the characteristic and noncharacteristic manifestations, phenotype-genotype correlations and knowledge of the underlying pathophysiologic mechanisms. This review provides a summary of the most important overgrowth syndromes aiming to familiarize the treating physician with the cardinal clinical features involved in these syndromes that encompass overgrowth, but also have a variety of other clinical manifestations (neurologic, musculoskeletal, skin, and accompanying tumors).

Early surgical treatment in unilateral coronoid hyperplasia and facial asymmetry.

Unilateral coronoid hyperplasia is a rare condition in the pediatric age. It may be an unrecognized cause of restricted mouth opening in children.The limited jaw movement is due to the enlargement of the coronoid process of the mandible that impinges on the zygomatic arch during mouth opening. This pathologic condition is still unknown and often misdiagnosed.Although in the past the term osteochondroma has been used to describe most of the unilateral and a few of the bilateral cases, there is no histologic evidence that the process has a neoplastic origin.Microscopic examination of the removed coronoid process has revealed hyperplastic compact bone covered with a thin layer of normal cartilage.There are multiple causes of mandibular hypomobility, each of them associated with different anatomic structures and etiologies, and a large number of cases, mostly bilateral, are idiopathic in nature.Several theories of pathogenesis have been proposed: temporomandibular joint dysfunctions, mandibular hypomobility, temporalis hyperactivity, hormonal stimulus, persistent cartilage growth center, genetic inheritance, and family factors.Unilateral coronoid hyperplasia is usually due to a trauma or a pathologic condition and is associated with facial asymmetry, being more frequently seen in women with histologic chondromatous or neoplastic changes. A thorough clinical history should include information about the onset and progression of pain and other subjective symptoms.In this study, we present a case of unilateral hyperplasia of the coronoid process in a 3 year-old female who, to the best of our knowledge, is the youngest patient so far reported with such anomaly.Our findings support the recommendation that early surgical treatment and aggressive postoperative physical therapy should be taken into account to allow for recovery of morphology and growth function in children.

Atypical goblet cell hyperplasia occurs in CPAM 1, 2, and 3, and is a probable precursor lesion for childhood adenocarcinoma.

Congenital pulmonary airway malformation (CPAM) is a developmental disorder. Types 1-2-3 are the more common ones. Atypical goblet cell hyperplasia (AGCH) in CPAM might be a precursor lesion for pulmonary adenocarcinomas. In nine out of 33 CPAM cases, types 1-3 showed foci of goblet cell proliferations. As these cells completely replace normal epithelium, we prefer to name these proliferations AGCH. In 5 cases, adenocarcinomas were seen (AC). All cases were analyzed for proteins possibly being associated with CPAM development: fibroblast growth factor 10 (FGF10) and receptor 2 (FGFR2), forkhead box A1 (FOXA1) and A2 (FOXA2), MUC protein 5AC (MUC5AC), human epidermal growth factor receptor 2 (erbB2, HER2/neu), hepatocyte nuclear factor 4α (HNF4α), SOX2, and Ying Yang protein 1 (YY1). By next generation sequencing, AGCH and adenocarcinomas were evaluated for driver mutations. Expression for FGF10, FGFR2, FOXA1, and FOXA2 was seen in CPAM epithelium and stroma, but not differently in AGCH and AC. SOX2 was positive in CPAM epithelium and AGCH, however weakly in AC. YY1 and MUC5AC showed more intense staining in AGCH and AC than in CPAM epithelium. HER2 was intensely expressed in AC and less intensely in AGCH, but not in CPAM epithelium. KRAS mutation in exon 2 was detected in all AGCH and AC, but was absent in CPAM epithelia. AGCH can arise in CPAM types 1-3. Oncogenic KRAS mutation seems to be the oncogenic driver already in AGCH, proving its role as a precursor lesion for adenocarcinoma. It might upregulate HER2 at the protein level. YY1 seems to be involved in carcinogenesis.

Carpal Tunnel Syndrome in Aberrant Muscle Syndrome: A Case Report and Review of the Literature.

Aberrant Muscle Syndrome (AMS) is a rare congenital hand difference that is characterised by unilateral non-progressive muscular hyperplasia. The aetiology of aberrant muscle syndrome is not known, but a recently published case has shown a somatic PIK3CA activating mutation in a patient with AMS. Carpal tunnel syndrome (CTS) in children is rare. The most common causes are the mucopolysaccaridoses but space-occupying lesions have also been reported to cause CTS in children. We report the first case of CTS in a child with AMS successfully treated with open carpal tunnel release and excision of aberrant muscles.

Androstenedione and its conversion to plasma testosterone in congenital adrenal hyperplasia.

The plasma concentration, production rate, and conversion ratio of androstenedione and testosterone were studied in seven children with congenital adrenal hyperplasia (CAH) of the 21-hydroxylase type. Plasma androstenedione and testosterone measured by double isotope derivative assay and estimated blood production rates were manyfold increased in the untreated state, markedly suppressed with glucocorticoid, and increased after the administration of ACTH. The metabolic clearance rate when corrected for body size and the conversion ratio of androstenedione to testosterone were similar to previously determined values in normal adults. Consideration of the androgen concentrations and conversion ratios indicates that in children with CAH, 76% of the plasma testosterone in prepubertal females and 36% in males are derived from peripheral conversion of blood androstenedione. The calculated amount of testosterone unaccounted for by peripheral conversion is similar to normal prepubertal values. This approach indicates that virilization in these children results from increased levels of testosterone but that the major source in CAH of this potent androgen is androstenedione secreted by the adrenal cortex.

Plasma progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia.

Plasma 17-hydroxyprogesterone (17-OHP) concentrations in normal men averaged 0.094 mug/100 ml. Studies using suppressive doses of androgens and glucocorticoids showed that 90% of the 17-OHP originated from the Leydig cell. The 17-OHP production rate was 1.8 mg/24 hr. Plasma 17-OHP has a marked circadian variation, the 8 p.m. values being only 40% of the 8 a.m. values. Plasma luteinizing hormone measured in the same samples did not vary. The adrenal cortex has the capacity to synthesize and secrete 17-OHP and progesterone since adrenocorticotrophic hormone (ACTH) caused a fourfold increase in these plasma steroids. In children with congenital adrenal hyperplasia, plasma 17-OHP levels were 50-200 times those of normal men and plasma progesterone was increased 6- to 10-fold over normal men.

New non-renal congenital disorders associated with medullary sponge kidney (MSK) support the pathogenic role of GDNF and point to the diagnosis of MSK in recurrent stone formers.

Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers.

A novel FOXF1 mutation associated with alveolar capillary dysplasia and coexisting colobomas and hemihyperplasia.

Alveolar capillary dysplasia (ACD) is a rare and lethal cause of hypoxic respiratory failure in the neonate. Here we describe a term neonate with ACD that was found with a previously unreported p.Arg86Pro mutation in the FOXF1 (Forkhead Box-F1) gene and coexisting congenital anomalies, including colobomas of the iris and hemihyperplasia. This unique clinical presentation may indicate a novel, yet unconfirmed disease association for mutations in the FOXF1 gene. Rapid mutation analysis in FOXF1 may provide noninvasive early confirmation of ACD in neonates with respiratory failure and can aid in clinical decision making.

Congenital interstitial cell of cajal hyperplasia with neuronal intestinal dysplasia.

Interstitial cells of Cajal (ICCs) are intestinal pacemaker cells that initiate peristalsis in the stomach and intestine, and are considered to be precursors of gastrointestinal stromal tumors (GISTs). We report a 2-year-old girl who suffered from scanty stool passage since birth. On barium enema, the distal colon was rigid with narrow lumen, whereas the proximal colon was dilated and atonic. She received right hemicolectomy and ileostomy. Histopathologically, there was continuous proliferation of spindle cells located between the layers of the muscularis propria throughout the right colon. These spindle cells were positive for c-kit and CD34 but negative for myogenic or neurogenic markers, indicating they are ICCs. No germline or somatic mutation of the juxtamembrane domain of c-kit gene was detected. In addition, the changes of the submucosal plexus fulfilled the histologic criteria of neuronal intestinal dysplasia type B. To our knowledge, this is the first reported case of congenital ICC hyperplasia. Further studies of ICC development may contribute to better understanding of the pathogenesis of this congenital malformation and the tumorigenesis of GIST.

Persistent hyperplastic primary vitreous (PHPV): role of computed tomography and magnetic resonance.

The diagnosis of PHPV is often made difficult by its extremely broad array of clinical manifestations, its etiologic heterogeneity, and frequently opaque ocular media. The CT and MR findings are discussed in terms of how they can be of use in the differential diagnosis of PHPV. The strengths and weaknesses of each of these diagnostic methods is detailed in regard to patients who present with unilateral leucocoria, microphthalmos, lens opacity, and retinal detachment.

Epidermal nevus syndrome with maxillary involvement.

A female patient with epidermal nevus syndrome is reported. There were linear epidermal nevi, hemihyperplasia of the limbs and tongue, macrocephaly, several ophthalmic malformations, and multiple radiolucent lesions in the limbs and sacroiliac region. At age 14 years, she developed a giant cell granuloma of the maxilla.

Cholesteatoma of the external auditory canal in hemifacial hypertrophy (hyperplasia).

Congenital hemifacial hypertrophy is an extremely rare condition. At the time of writing this article, there have been 37 cases reported in the literature. Of these, only two have appeared in the otolaryngologic literature. Cholesteatoma of the external auditory canal (EAC) in hemifacial hypertrophy has not been reported before. This article reports one such case, and discusses the classification of hemihypertrophies. A review of the literature is included in the discussion. Management of cholesteatomas of the external auditory canal is also touched upon. A new theory for the peculiar site selection of cholesteatomas of the external auditory canal is postulated.

[Congenital unilateral muscular hyperplasia of the hand - a rare malformation]. / Die kongenitale unilaterale Muskelhyperplasie der Hand - eine seltene Fehlbildung.

This is a report on eight cases of a rare congenital malformation in the upper extremity, consisting of a unilateral muscular hyperplasia. In addition to the hand, all segments of the upper extremity may be affected. The hyperplasia is always unilateral, preferably on the right hand side, in combination with accessory muscles. Hereditary dependence or association with other malformations has not been observed. Six of eight patients were male. Shoulder and arm function were normal in all cases. Ulnar drift of the fingers in the metacarpophalangeal joints (six of eight patients), flexion contractures of the metacarpophalangeal joints (six of eight patients) and extension contractures of the wrist (three of eight patients) to various degrees were seen. A prominence of the second and third metacarpal head with an enlarged space between them gave the affected hands a very typical appearance (six of eight patients). Deformities and functional limitations requiring surgical treatment were present in six patients. In all cases, accessory muscles were found intraoperatively and resected. The macroscopic and microscopic appearance of the muscle specimen did not differ from normal muscular tissue. In all cases, additional procedures were necessary to improve the overall function. Nevertheless, the reconstructive efforts did not lead to an entirely normal hand function or appearance. The malformation we describe can clearly be distinguished from other malformations such as arthrogryposis multiplex congenita, Freeman-Sheldon syndrome or macrodactyly. Up to now, only two other reports were found in the literature showing characteristics similar to those in our own cases. Four similar cases were observed by Benatar. From a pathomechanical point of view, a disturbance in the muscular balance seems to cause the deformities and functional limitations. This imbalance could be related to accessory muscles which are not opposed by defined antagonists or to an unbalanced hyperplasia of normally developed musculature. Surgical intervention should begin early to prevent joint stiffness. Splinting and hand therapy should precede surgical intervention. Surgical treatment should aim to restore the muscular balance by resection of accessory and hyperplastic musculature. In some cases, muscle transpositions and joint releases may have to be performed. Postoperative splinting and intensive hand therapy are mandatory to preserve the results.

Persistent hyperplastic primary vitreous in male twins.

Persistent hyperplastic primary vitreous (PHPV) occurs sporadically and few familial occurrences have been reported. The authors report PHPV unassociated with other congenital anomalies in male twins. One underwent a lensectomy for the management of angle-closure glaucoma and the other was treated for amblyopia. These cases provide further evidence to suggest autosomal recessive inheritance, though the possibility of developmental error cannot be excluded.

[Congenital homolateral epidermal hyperplasia and hypoplastic hemidysplasia (splitting of the Solomon's syndrome) (author's transl)]. / Hyperplasie épidermoque et Hémidysplasie corporelle hypoplasique congénitales homolatérales (Démembrement du syndrome de Solomon).

The observation of a 16-year-old girl born with an ectromelia and an ipsilateral inflammatory verrucous epidermal nevus led us to a synthetic study of 17 similar cases already published since 1927: all these cases concern female patients and are characterized by a unilateral hypoplastic dysplasia, most often of limbs, and inflammatory epidermal hyperplastic lesions described as ichthyosiform, psoriasiform or verrucous, usually distributed on the same side on the skin overlying the dysplastic body areas. The skin lesions may be partly regressive after birth and their histological features are suggestive of inflammatory linear verrucous epidermal nevus (I. L. V. E. N.). These associations may be representative of a special form of Solomon's syndrome whose heterogeneity has be recently emphasized. We propose to subdivide it in 3 forms: the epidermal nevus syndrome (Solomon's syndrome)--the organoid nevus syndrome (Schimmelpenning's syndrome)--the I. L. V. E. N. syndrome, probably X-linked dominant inherited (lethal for hemizygous males), associated with ipsilateral hypoplastic body lesions and, however less frequently than in the epidermal nevus syndrome, with ocular and nervous abnormalities. The distribution of cutaneous lesions has some similarities with the pattern of skin symptoms of X-linked dominant traits such as chondrodysplasia punctata, focal dermal hypoplasia or incontinentia pigmenti. The most typical feature of this syndrome is the strong inflammatory aspect of the epidermal nevus erroneously described in previous cases as unilateral psoriasis or ichthyosiform erythroderma.

Congenital diffuse hyperplastic goiter associated with perinatal mortality in 11 captive-born bottlenose dolphins (Tursiops truncatus).

Diffuse hyperplastic goiter was diagnosed by histopathology in 11 perinatal bottlenose dolphins (Tursiops truncatus) that died at four separate zoos and aquaria. Thyroid morphology of these animals was compared with the histologically normal thyroids of two stranded wild bottlenose dolphin calves, a neonate and a 2-mo-old calf. Histologic changes included reduced follicular luminal diameter, markedly reduced or absent luminal colloid, hypertrophy of follicular epithelium, and follicular dysplasia. The etiology of the thyroid gland lesion was not identified. Cause of death was not determined for most of these animals, but they were presumed to have died from metabolic derangements associated with the thyroid lesion, drowning, or dystocia.

Carpal tunnel syndrome in patient with hemihypertrophy: case report.

Carpal tunnel syndrome is a common condition; however, it has not been previously reported in patients with hemihypertrophy. A 67-year-old woman with left-sided hemihypertrophy presented with carpal tunnel syndrome of the left hand. Magnetic resonance imaging showed enlargement of the median nerve proximal to the transverse carpal ligament. Carpal tunnel decompression was performed, and pain was immediately relieved by decompression of the carpal tunnel. At the six-month follow-up examination, the patient experienced relief from numbness and improvement in thenar muscle atrophy was noted.