Seizure outcome and prognostic factors for surgical management of hypothalamic hamartomas in children.

PURPOSE: Hypothalamic hamartomas (HH) are rare benign lesions frequently associated with gelastic seizures early in life. Epilepsy can progress to multiple seizure types with cognitive impairment and behavioural disturbance, leading in some cases to epileptic encephalopathy. METHODS: We reviewed a retrospective series of 112 children treated in a single center, between 1998 and 2017. RESULTS: According to Delalande's HH classification, type1 was found in 2 patients, type 2 in 67, type 3 in 31, and type 4 in 12 patients. Stereotactic endoscopic disconnection was performed in 92 % of the procedures. Median age at diagnosis was 40 months and 7.6 years at surgery. Median time between diagnosis and surgery was 31 months and median follow up 4.1 years. For all HH types, 77.6 % of the patients had a favourable outcome (Engel I + II outcome score) with 57.1 % seizure-free (Engel I). The best outcome was obtained in patients with type 2 HH, (68.7 % Engel I and 85.1 % Engel I + II). The overall complication rate was 8.3 %, which is in line with previous series. Patients with isolated gelastic seizures had a better outcome (Engel I + II in 90 %), as compared to those with other seizure types (p = 0.07). A short delay between hamartoma diagnosis and surgery was a statistically significant factor for a good outcome (p = 0.03). CONCLUSION: Patients with HH and drug-resistant epilepsy should be early identified in order to propose surgical treatment without delay. Endoscopic disconnection is a safe and efficacious surgical option with good seizure outcome and immediate treatment results.

An Adult Case of Nasal Chondromesenchymal Hamartoma: Imaging Characteristics Including Diffusion-Weighted Images.

Nasal chondromesenchymal hamartoma (NCMH), a rare, benign, nasal cavity tumor, typically occurs in children. Differential diagnosis is difficult because NCMH often presents with non-specific findings, including cystic components and invasion of the surrounding area on T2-weighted magnetic resonance images. Here, we present a rare adult case of NCMH, with no clear hyperintensity on diffusion-weighted images (DWI), and bone remodeling on the tumor margins on computed tomography. To the best of our knowledge, this is the first report of DWI on NCMH, and these findings, which suggest benign disease, may be useful in diagnosing NCMH.

Loss of succinate dehydrogenase B immunohistochemical expression distinguishes pulmonary chondromas from hamartomas.

AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.

NOVEL CLASSIFICATION SYSTEM FOR COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.

PURPOSE: To develop an anatomical classification scheme for combined hamartoma of the retina and retinal pigment epithelium (RPE) and specify recommendations for follow-up interval. METHODS: Retrospective review of patients with combined hamartoma of the retina and RPE examined during a 7-year period (2008-2015). The clinical presentation, fundus examination, and optical coherence tomography were analyzed. RESULTS: Lesions were classified based on location, fundus features, and optical coherence tomography findings. Lesion location: macular/peripapillary-Zone 1; mid-periphery-Zone 2; and far periphery-Zone 3. Associated fundus findings: no retinal traction-Stage 1; retinal traction and/or retinoschisis-Stage 2; and retinal detachment-Stage 3. Optical coherence tomography findings: epiretinal component only-A; partial retinal involvement-B; and complete retinal and RPE involvement-C. Complete ophthalmologic evaluation is recommended at least every 6 months for patients younger than 12 years, with more frequent follow-up in patients with: lesions in the macula/peripapillary (Zone 1) or with retinal traction, retinoschisis, or retinal detachment (Stage 2 and 3). Surgical intervention is recommended in patients with vision loss secondary to macular traction or retinal detachment. CONCLUSION: A new clinical classification system is proposed for evaluating and managing patients with combined hamartoma of the retina and RPE. The zone and stage of combined hamartoma of the retina and RPE lesion will assist in determining follow-up interval and surgical intervention. Application of a uniform classification scheme will facilitate assessment and comparison of findings across different studies.

Ectopic Hamartomatous Thymoma: A Review Of The Literature With Report Of New Cases And Proposal Of A New Name: Biphenotypic Branchioma.

Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm of the lower neck suggesting branchial origin. Despite use of the term thymoma in the nomenclature, there is no evidence of thymic origin or differentiation. It affects middle-aged adults with a remarkable male predominance. To date less than 80 cases have been reported in the English literature. We present here two additional cases of EHT. The first is a benign case in a 31-year-old man, showing typical histological features. The second is a malignant case in a 70-year-old woman, showing intraductal carcinoma arising in intimate association with an EHT. These cases are presented in the context of a review of cases reported in the English literature. The exact origin has not been identified, but is considered to be of branchial apparatus, creating a quandary about the best terminology. Recently, the designation "branchial anlage mixed tumor" or "thymic anlage tumor" were proposed, but do not quite reflect the true nature of the neoplasm. To avoid taxonomic confusion, international consensus on terminology is desired. As this entity is a neoplasm that shows dual mesoderm and endoderm derivation/differentiation, we propose a new name "biphenotypic branchioma."

RETINAL ASTROCYTIC HAMARTOMA: Optical Coherence Tomography Classification and Correlation With Tuberous Sclerosis Complex.

PURPOSE: To propose a classification of retinal astrocytic hamartoma based on spectral domain optical coherence tomography and correlate each class with systemic manifestations of tuberous sclerosis complex. METHODS: Retrospective chart review conducted at four international referral medical retina centers. There were 43 consecutive patients with an established diagnosis of tuberous sclerosis complex based on presence of at least 2 major or 1 major and 2 minor features of the diagnostic criteria. Clinical and spectral domain optical coherence tomography features regarding retinal astrocytic hamartoma were documented. RESULTS: The mean patient age at presentation was 16.2 years. The retinal astrocytic hamartoma was classified as Type I (n = 41), Type II (n = 25), Type III (n = 20), or Type IV (n = 12). Patients with Type II showed greater number of cutaneous fibrous plaques (odds ratio = 64.8; 92% confidence interval: 64.2-65; P < 0.001); those with Type III displayed higher incidence of subependymal giant-cell astrocytomas (odds ratio = 43.2; 95% confidence interval: 43.0-43.3; P < 0.001); and those with Type IV showed higher incidence of pulmonary lymphangiomyomatosis (odds ratio = 126; 95% confidence interval: 122-128; P < 0.001). CONCLUSION: Retinal astrocytic hamartoma can be classified into four morphologic groups, based on spectral domain optical coherence tomography. There are important systemic tuberous sclerosis complex correlations with each class.

Classification of cysts with follicular germinative differentiation.

BACKGROUND: Cysts are very common in the routine of dermatopathology but follicular germinative (trichoblastic) differentiation in cysts is seen rarely. The presence of follicular germinative differentiation in a cyst alerts to consider the possibility of a basal cell carcinoma (BCC) arising in a cyst. METHODS: Five cystic lesions with zones of follicular germinative differentiation were collected. Hematoxylin and eosin sections were reassessed for architecture, types of follicular differentiation and stromal characteristics; immunohistochemical studies with Ber-EP4 were analyzed. Articles about follicular germinative differentiation in cystic lesions were reviewed. RESULTS: Cystic lesions with follicular germinative differentiation have been described in the literature under various names including trichoblastic infundibular cyst, cystic trichoblastoma, cystic panfolliculoma (CPF), dermoid cyst with basaloid proliferations, folliculosebaceous cystic hamartoma and BCC occurring in infundibular cysts. The lesions presented by us could be classified as three cystic trichoblastomas, one CPF and one cystic hamartoma with follicular germinative differentiation. CONCLUSIONS: Histopathologically, cystic trichoblastomas can be separated from CPFs. Some lesions defy classification and may be regarded as cystic follicular hamartomas. The presence of follicular papillae and bulb-like structures, advanced follicular differentiation like that of inner and outer root sheath exclude the differential diagnosis of BCC arising in a cyst.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

Hamartoma mesenquimal rabdomiomatoso: um relato de caso / Rhabdomyomatous mesenchymal hamartoma: a case report

The rhabdomyomatous mesenchymal hamartoma (RMH) is a rare type of hamartoma, composed of randomly arranged striated muscle fibers in dermis and subcutaneous tissue, associated with normal mesenchymal elements. Our objective is to report a case of this rare entity that occurred in the nasal dorsum of a 4-year-old child...

O hamartoma mesenquimal rabdomiomatoso (HMR) representa um raro tipo de hamartoma composto por fibras musculares estriadas dispostas aleatoriamente em derme e tecido subcutâneo, associadas a elementos mesenquimais normais. O nosso objetivo é relatar um caso desta rara entidade que ocorreu no dorso nasal de uma criança de 4 anos...

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis.

Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed leiomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.

Classification of hypothalamic hamartoma and prognostic factors for surgical outcome.

OBJECTIVES: The main aims of this study were to classify patients with hypothalamic hamartoma (HH) based on neuroimaging features and describe the clinical manifestations of HH. MATERIALS AND METHODS: A retrospective review of 214 consecutive patients with HH treated in Beijing Tiantan Hospital was performed. RESULTS: HH were diagnosed and divided into Types I-IV based on MRI. Types I and II were defined as the HH attached to the floor of the third ventricle with narrow (Type I) or broad (Type II) interfaces. Type III ('straddling') was defined by the HH extending into the third ventricle and interpeduncular cistern. Type IV was defined as the HH located totally within the third ventricle. The percent distribution of patients was 35.9% Type I, 12.1% Type II, 40.7% Type III, and 11.2% Type IV. The percentage of patients with precocious puberty was highest in Type I (81.8%). The percentage of patients with gelastic seizures was highest in Type IV (91.7%). After surgery, 20% (1/5) of patients with Type II HH, 48.8% (20/42) with Type III, and 91.7% (11/12) with Type IV were free of epileptic seizures. Significant prognostic factors for surgical outcome were HH size, surgical approach, and resection level. CONCLUSIONS: The clinical manifestations of HH are correlated with the topology of the HH in relation to the hypothalamus. Our results suggest that patients with Type IV HH have the best outcome from surgery and neurosurgeons should be cautious about performing surgery on patients with Type II and Type III HH.

Optic pathway gliomas: neoplasms, not hamartomas.

IMPORTANCE: Optic pathway gliomas are an important neuro-ophthalmic cause of vision loss in children. Their management depends on whether they are considered neoplasms or hamartomas. OBJECTIVE: To outline the evidence that optic pathway gliomas are slowly growing neoplasms and not hamartomas. DESIGN: Review of relevant studies in the literature. SETTING: The authors are from a pediatric tertiary referral center. RESULTS: The growth patterns and histopathology of optic pathway gliomas are more consistent with those of neoplasms. Spontaneous regression, thought to be a characteristic of hamartomas, can be seen in neoplasms of other types as well as in optic pathway gliomas. Chemotherapy used in low-grade gliomas has been shown to halt or improve vision loss in optic pathway gliomas in many cases. CONCLUSIONS AND RELEVANCE: Optic pathway gliomas are not hamartomas but truly are neoplasms. Thus, patients should be followed up closely, and chemotherapies should be used when clinical progression occurs. Other more directed therapies will certainly be used in the future.

Subependymal glioneuronal hamartoma in the mesencephalic aqueduct of a giraffe.

A 1-day-old male giraffe calf (Giraffa camelopardalis) was submitted for necropsy examination after sustaining postnatal head trauma from the cow. In addition to the expected findings of severe cerebral edema and epidural and subarachnoid hemorrhage, there also was present an incidental finding of a subependymal glioneuronal aqueductal hamartoma. Reports of this type of congenital lesion are rare in the human literature, and the lesion has not, to the authors' knowledge, previously been reported in this or any other veterinary species.

Repeat surgery for hypothalamic hamartoma in refractory epilepsy.

OBJECT: Hypothalamic hamartomas (HHs) often cause pharmacoresistant epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Surgical intervention offers the patient the best opportunity of seizure resolution, which occurs in approximately 50%­60% of patients, and improvement in both cognitive and behavioral difficulties. For those in whom the initial operation has failed, further medical treatment options remain quite limited, whereas, in some cases, a second surgery may improve seizure outcome. The authors retrospectively reviewed their surgical cases to document the success rate and complications of reoperations in patients with HHs. METHODS: Data were obtained from the HH epilepsy surgery database at the Barrow Neurological Institute between 2003 and 2010. Surgical treatment consisted of open and endoscopic procedures, as well as radiosurgery. Demographic details, seizure history, presurgical evaluation, and postoperative follow-up data were evaluated. RESULTS: In the last 7 years, 21 (13%) of 157 patients underwent reoperation after an initial epilepsy operation. The initial surgical approach in the 21 patients included: endoscopic (8 patients [38%]), transcallosal (8 patients [38%]), orbitozygomatic (3 patients [14%]), and radiosurgery (2 patients [10%]). Of the 8 patients who initially underwent endoscopic resection, repeat procedures included: radiosurgery in 4 (50%), an orbitozygomatic approach in 2 (25%), repeat endoscopy in 1 (12.5%), and a transcallosal approach in 1 (12.5%). Repeat procedures after an initial transcallosal resection included: endoscopic resection in 2 (25%); radiosurgery in 1 (12%); an orbitozygomatic approach in 2 (25%), and repeat transcallosal surgery in 3 (38%). Predominant seizure types that recurred after the first surgery were gelastic seizures, complex partial seizures, and tonic-clonic seizures. Magnetic resonance imaging in all patients prior to reoperation demonstrated either residual HH and/or connection with the mammillary bodies. Review of patients with more than 6 months of follow-up since the last surgery showed greater than 90% reduction in seizures in 4 patients (19%) and by 50%­90% in 10 patients (48%). Two patients were seizure free, and in 5 patients (24%) there was no change in seizure frequency. Following reoperation, none of the patients had any worsened behavioral issues such as increased rage attacks or disruptive violent behavior. New postoperative complications after reoperation included hemiparesis, thalamic stroke (asymptomatic and symptomatic), hyperphagia, and panhypopituitarism. CONCLUSIONS: Reoperation should be considered in selected patients with HH in whom initial epilepsy surgery fails because more than half the patients have significant reductions in seizure.

Epidermal nevi.

Nevi or nests of cells may be made up of a variety of cell types. The cell types that live in the epidermis include epidermal cells or keratinocytes, sebaceous glands, hair follicles, apocrine and eccrine glands, and smooth muscle cells. This article discusses epidermal or keratinocyte nevi, nevus sebaceous, nevus comedonicus, smooth muscle hamartomas, and inflammatory linear verrucous epidermal nevi. Syndromes associated with epidermal nevi are also reviewed.

Canine mesenchymal hamartoma of the eyelid.

OBJECTIVE: Characterization of a benign disease syndrome involving the eyelids of dogs, describing the signalment, clinical appearance, anatomic location, and pathologic features. ANIMAL STUDIED: The records and submitted tissue of 10 dogs with mesenchymal hamartomatous lesions of the periocular connective tissues were retrieved from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database. PROCEDURE: The submitted tissue in each case was stained with hematoxilyn & eosin and Masson's Trichrome stain and examined histopathologically. Clinical information was collected from the submission requests. The clinical history, treatment, and follow-up are described in more detail for one of the 10 dogs. RESULTS: Seven different breeds, including four Golden Retrievers, were represented. The ages of affected dogs ranged from 6 to 11 years. Eight of 10 lesions were located at the temporal canthus, ranging in diameter from 0.6 to 3 cm. Clinically, the masses were subcutaneous, firm, lobular soft-tissue growths, which were in some cases adherent to the underlying orbital rim, and in others, freely palpable between the skin and conjunctiva of the eyelid. Histologically, all had distinct margins but were not encapsulated and contained normal appearing collagen-rich connective tissue with some adipose tissue. Five also contained fully differentiated skeletal muscle tissue arranged in poorly formed aggregates or as individual muscle fibers. CONCLUSION: Mesenchymal hamartoma of the eyelid has not been previously described. The mass has a predisposition to occur at the temporal canthus and should be included in the list of differential diagnoses of benign eyelid masses in dogs.

Giant and complicated variants of cystic bile duct hamartomas of the liver: MRI findings and pathological correlations.

PURPOSE: To describe a new category of liver cyst we propose calling "giant bile duct hamartoma (giant-BDH)" and to provide a more complete record of the magnetic resonance imaging (MRI) features of BDHs with potential for clinical impact. MATERIALS AND METHODS: This study was Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPPA)-compliant. Fifteen patients were identified with surgical liver pathology in keeping with complicated BDH and MRI findings of giant cysts. RESULTS: In all, 14/15 patients presented with pain that resolved in 14/14 with surgery. Imaging features common to pretreatment cysts included sharply defined, lobulated margins with thin, smooth rim-enhancement. Treated symptomatic cysts measured 9.8 cm on average and 21.6 cm maximum. The 14/15 patients had coexistent <2.0 cm BDH. Elevated T1 signal corresponded with hemorrhagic cyst content (10/15 patients); cyst-wall rim-enhancement corresponded with histological findings of inflammation (15/15), fibrocystic changes (12/15), and smaller BDH in the adjacent liver (13/15). Histology of giant-BDH cyst walls corresponded with complicated BDH in 15/15. The incidence of symptomatic-treated BDH at our institution was 0.4%. CONCLUSION: BDH is a benign hepatic cystic lesion that may undergo cystic enlargement, internal hemorrhage, and clinically present with abdominal pain treatable by minimally invasive laparoscopic fenestration. Complicated giant-BDH coexists with smaller BDH and the MRI features of giant-BDH are characteristic.

A revaluation of folliculosebaceous cystic hamartoma: the histopathological and immunohistochemical features.

The histogenesis of folliculosebaceous cystic hamartoma (FSCH), including the origin of the frequently associated adipocytes and other mesenchymal components, remains unclear. There are controversial problems regarding FSCH, such as the relationship between FSCH and trichofolliculoma (TF), and the exact concept of sebaceous TF. Fourteen FSCHs and 1 sebaceous TF were revaluated for the histopathology and studied for immunohistochemical profile of various cytokeratins, hair follicular stem cell markers, and others. The nestin expression was partly upregulated in the sebaceous duct structures and the proliferating spindle cells in the surrounding connective tissue in some lesions. S-100 protein staining clarified the presence of lipogenesis in these nestin-expressed lesions, and the nestin-positive spindle cells were also seen around the immature adipocytes. Some FSCHs showed the focal follicular differentiation, where no signs of catagen or telogen stage were seen. One peculiar case showed both FSCH and TF features equally. The possibility that the adipocytes and other mesenchymal components in FSCHs originated from the nestin-positive multipotent stem cells was suggested. It is not convincing that FSCH and TF represent a chronological change in the spectrum of the same condition. Each FSCH and TF is therefore considered to be a distinctive entity. They may develop under a similar pathogenesis differing from each other in the direction of fundamental differentiation. In contrast to the TF lesions, the unusual upregulation of nestin expression is occasionally seen in FSCH lesions, including their stromas, which may thus result in the production of various kinds of mesenchymal components in FSCHs.