[Subcutaneous and intramuscular heterotopic calcification of the neck 42 years after radiotherapy]. / Subcutan és intramuscularis heterotop kalcifikáció a nyakon 42 évvel a sugárkezelést követoen.

Radiotherapy-induced heterotopic tissue calcification is an exceedingly rare complication in the head and neck region. We report a patient with extensive, radiotherapy-induced, combined subcutaneous and intramuscular, heterotopic calcification of the neck. An 80-year-old male presented with a 2-month history of severe dysphagia and a painful ulcer on the neck 42 years after salvage total laryngectomy following radiotherapy (total dose: 80 Gy) for a T3N0M0 glottic squamous cell carcinoma. We excluded recurrence or secondary malignancy by biopsy and performed computed tomography, which revealed subcutaneous and intramuscular calcification in the area of the skin ulcer and close to the hypopharyngeal wall, moreover, total occlusion of the common carotid and vertebral arteries bilaterally. Surgical correction involved removing the calcified lesions and closure using fasciocutaneous flap transposition. The patient has been asymptomatic for the past 48 months. Radiotherapy plays an essential role in the treatment of patients with head and neck squamous cell carcinoma. Distorted postoperative anatomy, excessive scar formation, radiotherapy-induced fibrosis as well as skin and subcutaneous tissue calcification can present as atypical findings. Orv Hetil. 2023; 164(10): 383-387.

Adenocarcinoma arising in the multiple heterotopic submucosal glands of the intestine in a Satoyoshi syndrome patient: A case report.

Satoyoshi syndrome is a rare multisystemic disorder of unknown etiology characterized by progressive muscle spasms, alopecia and diarrhea. Multiple protruding lesions with cystic glands, namely gastroenterocolitis cystica polyposa, manifest in the gastrointestinal tract. Since the first report of these lesions in 1977, which was unique to Satoyoshi syndrome, few studies have focused on their role, and the associated clinicopathological features are not well understood. Here, we report a 64-year-old Japanese woman with Satoyoshi syndrome who presented with multiple polypoid lesions in the stomach, duodenum, jejunum, ileum and colon. Histologically, the polypoid lesions in the intestine comprised multiple heterotopic submucosal glands containing cystically dilated glands and smooth muscle fibers in the lamina propria mucosa and/or submucosa. Additionally, we observed stromal changes, such as fibrosis, discontinuous and thinning muscularis mucosae, and diffuse neural fiber proliferation in the entire intestinal tract. Furthermore, multiple foci of adenocarcinomas were identified within several heterotopic submucosal glands. We hypothesized that multiple heterotopic submucosal glands in the present case corresponded to previously reported gastroenterocolitis cystica polyposa, suggesting that these lesions are essential in the histopathology and are a unique manifestation of Satoyoshi syndrome.

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

OBJECTIVES: To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS: Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS: Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4+CXC-motif chemokine receptor 5 (CXCR5)+programmed cell death protein 1 (PD1)+ICOS+ Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4+CD45RO+ICOS+PD1+ cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5+CD4+PD1+ICOS+Foxp3- Tfh-cells and a uniquely expanded population of CXCR5-CD4+PD1hiICOS+Foxp3- Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS: Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.

An Uncommon Focal Liver Lesion: Intrahepatic Splenosis.

Multiple focal liver lesions were incidentally detected in a patient screened by ultrasound for a recent diagnosis of lower limb deep vein thrombosis, for which anticoagulation had been initiated. Past medical history reported a post-traumatic splenectomy 15 years before. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) showed a subcapsular lesion in liver segment 5 consistent with focal nodular hyperplasia (FNH) and multiple other nodules, with a different pattern from the former, judged as probable hepatic adenomas by MRI but probable hemangiomas by CEUS (hyperenhancement in the late phase). Therefore, another MRI with gadoxetic acid was performed. The diagnosis of FNH was confirmed. The other lesions showed an hyperenhancing pattern in the arterial phase with progressive wash-out in the portal and late phase and marked hypointensity in the hepatobiliary phase. This pattern apparently confirmed the hypothesis of adenomas, with a potential risk of malignancy due to the hepatobiliary phase pattern and the recent occurrence of deep vein thrombosis. Due to the inherent risk of spontaneous bleeding from subcapsular adenomas increased by the ongoing anticoagulant therapy and the recommendation of international guidelines to resect adenomas in male subjects, the patient was directly offered surgery. Pathology of the resected specimens confirmed one FNH but demonstrated intrahepatic splenosis for all other lesions. This case suggests that in the setting of previous splenic trauma any discrepancy between MRI and CEUS findings should lead one to consider also the hypothesis of intrahepatic splenosis.

Development of a Meniscal Ossicle After a Meniscal Root Repair Augmented with Bone Marrow Aspirate Concentrate: A Case Report.

CASE: A 17-year-old boy had persistent knee pain 1 year after medial meniscal root repair augmented with bone marrow aspirate concentrate injection. Radiographs and magnetic resonance imaging (MRI) demonstrated an intrameniscal ossicle which was not present on MRI performed before 6 months. He underwent arthroscopic excision of the meniscal ossicle. At the 7-month follow-up, he had complete relief of his pain. CONCLUSIONS: It is possible that the meniscal ossicle developed because of osteoinductive cells and cytokines from the injected bone marrow or the drill hole for root repair and should be considered as a possible complication of this procedure.

Ectopic brown adipose tissue formation within skeletal muscle after brown adipose progenitor cell transplant augments energy expenditure.

Brown adipose tissue (BAT) thermogenesis increases energy expenditure (EE). Expanding the volume of active BAT via transplantation holds promise as a therapeutic strategy for morbid obesity and diabetes. Brown adipose progenitor cells (BAPCs) can be isolated and expanded to generate autologous brown adipocyte implants. However, the transplantation of brown adipocytes is currently impeded by poor efficiency of BAT tissue formation in vivo and undesirably short engraftment time. In this study, we demonstrated that transplanting BAPCs into limb skeletal muscles consistently led to the ectopic formation of uncoupling protein 1 (UCP1)+pos adipose tissue with long-term engraftment (>4 mo). Combining VEGF with the BAPC transplant further improved BAT formation in muscle. Ectopic engraftment of BAPC-derived BAT in skeletal muscle augmented the EE of recipient mice. Although UCP1 expression declined in long-term BAT grafts, this deterioration can be reversed by swimming exercise because of sympathetic activation. This study suggests that intramuscular transplantation of BAPCs represents a promising approach to deriving functional BAT engraftment, which may be applied to therapeutic BAT transplantation and tissue engineering.-Liu, Y., Fu, W., Seese, K., Yin, A., Yin, H. Ectopic brown adipose tissue formation within skeletal muscle after brown adipose progenitor cell transplant augments energy expenditure.

Urospermia indicating ectopic ureters in breeding dogs - 3 cases.

An Entlebucher Mountain Dog (57 months old, case 1), a Labrador Retriever (24 months, case 2) and an Irish Soft-Coated Wheaten Terrier (31 months old, case 3) were presented for breeding soundness evaluation to the clinic. During semen collection in all 3 dogs, the pre-secretion and the sperm-rich fraction showed normal consistency and colour, whereas the prostatic secretion (3 rd ejaculate fraction) appeared strikingly yellow. In cases 1 and 2, a severely decreased sperm motility (asthenozoospermia) and an increased amount of abnormal spermatozoa (teratozoospermia), and in case 3, a moderately decreased total sperm count (oligozoospermia) were detected. Sonographical examination revealed abnormal findings regarding the uretero-vesical junction and ectopic ureters. Therefore it is concluded that urine admixture to the 3 rd ejaculate fraction may indicate the presence of ectopic ureters and may cause impairment of semen quality and fertility. The present cases raise questions regarding urospermia concerning: 1. its incidence in dogs in general and in connection with ectopic ureters and 2. its relevance as a cause of deficient ejaculate quality and subfertility or infertility.

An ectopic adrenocortical adenoma in renal hilum presenting with Cushing's syndrome: A case report and literature review.

RATIONALE: Ectopic adrenal tissue is the adrenal rests along the path from gonads to adrenal glands during embryogenesis. Ectopic adrenocortical adenoma is a rare disease represented with over-production of cortisol by the ectopic adrenocortical tissue. PATIENT CONCERNS: An 18-year-old Chinese female patient was presented with weight-gain for 6 months. She had elevated plasma cortisol and a solitary mass was revealed using computed tomography scan in the left renal hilum. DIAGNOSIS: The tumor was removed and the immunohistochemical profile indicated an ectopic adrenocortical adenoma. INTERVENTIONS: After the tumor was removed, the patient was under glucocorticoid replacement therapy in 6-month. OUTCOMES: During 6-month of follow-up, the patient showed no signs of tumor recurrence. LESSONS: Ectopic adrenocortical adenoma is difficult to diagnose due to its low incidence, and the ectopic rests in renal hilum could be misdiagnosed as renal cell carcinoma. This case reminds clinicians to be aware of ectopic site in the diagnosis of adrenocorticotropic hormone (ACTH) independent Cushing's syndrome. Immunohistochemical stain may assist in evaluating the origin of the ectopic rests. A certain rate of local recurrence indicated the need of long-term follow-up.

Hydronephrosis Secondary to an Ectopic Decidual Reaction in the Urinary Bladder.

A 28-year-old pregnant woman at 19 weeks gestation presented with dysuria as well as lower abdominal and left flank pain. Imaging revealed left-sided hydronephrosis and a mass invading the posterior bladder wall. Management included placement of a left nephrostomy tube and transurethral resection of ~25% of the mass. Microscopy showed an ectopic decidual reaction within the muscularis propria. The patient improved symptomatically and continued prenatal care. Complete resolution of her ureteral obstruction was demonstrated during the postpartum period. Ectopic decidual reactions involving the urinary bladder are extremely rare, and ureteral obstruction secondary to this phenomenon has not yet been reported.

[Intrathyroidal location of parathyroid glands. Atypical presentation of multiple endocrine neoplasia type 1 syndrome]. / Localización intratiroidea de glándulas paratiroides. Presentación atípica del síndrome de neoplasia endocrina múltiple tipo 1.

BACKGROUND: The most common manifestation of MEN 1 syndrome is primary hyperparathyroidism (PHPT) with parathyroid multiglandular affectation. The intrathyroidal situation represents 3-4% of all glands, and it is the second most frequent location in the cervical ectopias. CLINICAL CASE: 11 year old patient, with a family history of MEN1 syndrome and carrier of this same mutation. Patient presents HPTP with osteopenia. The cervical ultrasound shows three compatible images with pathological parathyroid glands (bilateral lower and upper left). The Scan and MRI are normal. Bone densitometry displays data on osteopenia. The patient is surgically intervened, only the upper parathyroid glands are located and removed, after this implantation is performed on the forearm, to prevent the possible devascularization in the dissection of the other glands. However, osteopenia persists and an elevated PTH, therefore new diagnostic tests are held which seem to show two lower parathyroid glands with intrathyroidal location. The patient is reoperated. A subtotal parathyroidectomy of the lower right gland and the resection of the left gland is performed, with the use of intraoperative ultrasound and placement of harpoon. The intraoperative pathology study confirms parathyroid tissue in both cases. DISCUSSION: It is necessary to locate the parathyroid glands preoperatively in order to alert us of the existence of topographical and ectopia abnormalities, as well as their intrathyroidal location (0.5-3.6%). CONCLUSION: The intraoperative ultrasound can be a complement to the experience of the endocrine surgeon for the localization of the parathyroid glands and therefore can help determine the best surgical strategy for each clinical case.

Respiratory epithelial cysts of the orbit.

To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence.

Immunohistochemical Characterization of the Ectopic Epithelium Devoid of Goblet Cells From a Posttraumatic Iris Cyst Causing Mucogenic Glaucoma.

PURPOSE: Mucogenic glaucoma is an unusual form of secondary open-angle glaucoma caused by intracameral ectopic mucus-producing epithelium. To date, only 3 cases have been described in detail. Numerous goblet cells in the specimens indicated a possible conjunctival origin. We immunohistochemically characterized the implanted epithelium from an iris cyst responsible for mucogenic glaucoma. METHODS: A series of immunostaining analyses were performed on a sector-iridectomy specimen derived from an eye with mucogenic glaucoma and a history of limbal penetrating injury. An iris cyst was present in the inferonasal quadrant of the right eye of a 58-year-old man. The anterior chamber was filled with hazy, translucent material, and the chamber angle was gonioscopically open. The cyst was resected due to medically uncontrollable high intraocular pressure. RESULTS: The ectopic epithelium was mostly positive for CK19, a corneal and conjunctival epithelial marker. Negative staining for MUC5AC, a secretory mucin, and positive staining for MUC1, a membrane-bound mucin, corroborated the absence of goblet cells. Ectopic epithelial cells were abundantly positive for CK15, a limbal basal cell marker, but there was patchy immunostaining of CK13, a conjunctival epithelial marker, and sparse labeling with CK12, a corneal epithelial marker. Immunostaining patterns of CK15, CK13, and CK12 were nearly mutually exclusive. CONCLUSIONS: The ectopic epithelium of an iris cyst causing mucogenic glaucoma was most likely to originate from limbal basal cells, which showed dual direction of differentiation toward both the conjunctival and corneal epithelia. The membrane-bound mucin may have caused mucogenic glaucoma in the absence of goblet cells.

Onychoheterotopia Due to a Traumatically Transplanted Nail in a Child.

Onychoheterotopia is a rare condition characterized by ectopic nail tissue growth. It is a digital mass that is commonly misdiagnosed. We describe a 6-year-old girl who presented with onychoheterotopia after trauma to the digit. Her onychoheterotopia was incorrectly diagnosed as a common wart. It is important to include onychoheterotopia in the differential diagnosis of digital masses, especially in the setting of previous traumatic injury.

Long-Term Extensive Ectopic Hair Growth on the Spinal Cord of Mice from Transplanted Whisker Follicles.

We have previously demonstrated that hair follicles contain nestin-expressing pluripotent stem cells that can effect nerve and spinal cord repair upon transplantation. In the present study, isolated whisker follicles from nestin-driven green fluorescent protein (ND-GFP) mice were histocultured on Gelfoam for 3 weeks for the purpose of transplantation to the spinal cord to heal an induced injury. The hair shaft was cut off from Gelfoam-histocultured whisker follicles, and the remaining part of the whisker follicles containing GFP-nestin expressing pluripotent stem cells were transplanted into the injured spinal cord of nude mice, along with the Gelfoam. After 90 days, the mice were sacrificed and the spinal cord lesion was observed to have healed. ND-GFP expression was intense at the healed area of the spinal cord, as observed by fluorescence microscopy, demonstrating that the hair follicle stem cells were involved in healing the spinal cord. Unexpectedly, the transplanted whisker follicles sprouted out remarkably long hair shafts in the spinal cord during the 90 days after transplantation of Gelfoam whisker histocultures to the injured spine. The pigmented hair fibers, grown from the transplanted whisker histocultures, curved and enclosed the spinal cord. The unanticipated results demonstrate the great potential of hair growth after transplantation of Gelfoam hair follicle histocultures, even at an ectopic site.

Thoracic cord herniation and associated intra-operative nuances: a report.

BACKGROUND: Thoracic cord herniation is a well-established entity in the literature. Majority of the published literature deals with its surgical management in terms of "mere" detethering of cord. However, not much is written about the degree of herniation and ectopic cord tissue and its management. A 58-year-old male presented to us with progressive difficulty in walking. Imaging revealed a cord herniation at T7-8 level. Surgical detethering was planned. However, a significant amount of "ectopic" cord tissue was found outside the dural defect intra-operatively. Simple detethering and repositioning was difficult. Hence, the ectopic tissue was excised under neuro-physiologic monitoring and no major change was recorded intra-operatively/post-operatively. CONCLUSIONS: Thoracic cord herniation surgery may be more than simple detethering and cord repositioning. If encountered in similar situations intra-operatively, surgeons should be able to excise ectopic tissue without grave post-operative deficits. Neuronal plasticity probably plays an important role in the pathophysiology of long-standing cord herniation.

Causes and consequences of gray matter heterotopia.

The objective of this article is to review the pathophysiological bases of gray matter heterotopia and to appreciate their involvement in brain cortical development and functional consequences, namely epilepsy. The development of the cerebral cortex results from complex sequential processes including cell proliferation, cell migration, cortical organization, and formation of neuronal networks. Disruption of these steps yields different types of cortical malformations including gray matter heterotopia, characterized by the ectopic position of neurons along the ventricular walls or in the deep white matter. Cortical malformations are major causes of epilepsy, being responsible for up to 40% of drug-resistant epilepsy, and the cognitive level of affected patients varies from normal to severely impaired. This review reports data from human patients and animal models highlighting the genetic causes for these disorders affecting not only neuronal migration but also the proliferation of cortical progenitors. Therefore, gray matter heterotopias should not be considered as solely due to an abnormal neuronal migration and classifying them as such may be too restrictive. The review will also summarize literature data indicating that besides ectopic neurons, neighbor cortical areas also play a consistent role in epileptogenesis, supporting the notion that plastic changes secondary to the initial malformation are instrumental in the pathophysiology of epilepsy in affected patients.