ALK-Positive Histiocytosis: A Case Report and Literature Review.

ALK positive histiocytosis is a relatively new histiocytic proliferation disease with a characteristic gene translocation involving fusion of the ALK gene with different partners, mostly KIF5B. We report a case of ALK-positive histiocytosis with literature review. A 27-year-old male patient presented mainly with progressive lower limb weakness. Imaging studies showed an intradural extramedullary enhancing lesion at the L3 level. A 1.5 cm mass was excised from the sensory nerve root in the filum terminale at the level of L3. Histologic examination showed infiltration of the nerve by numerous histiocytes with moderate to abundant eosinophilic to clear-foamy and variably-vacuolated cytoplasm with irregular-to-smooth contoured nuclei. The histiocytes were positive for CD68 and ALK1 and negative for S100 and CD1a. KIF5B-ALK fusion was detected by real time-polymerase chain reaction. The patient is asymptomatic nine months after surgical excision. This is the first reported localized case occurring in the nerve root of an adult patient, thus expanding the clinical manifestations of this disease. An integrated histological, immunohistochemical and molecular approach is recommended for diagnosis. We recommend performing ALK1 immunohistochemical stain on all histiocytosis cases to increase awareness and detection of this newly described entity.

Line-field confocal optical coherence tomography of xanthogranuloma: Correlation with vertical and horizontal histopathology.

Line-field confocal optical coherence tomography (LC-OCT) is a new noninvasive technique for a real-time, vertical, and horizontal imaging of the skin at cellular resolution. A 47-year-old female presented with a 6-month history of an asymptomatic yellowish papule. LC-OCT evaluation was able to show the diagnostic microscopic features of xanthogranuloma and showed an excellent correlation with vertical and horizontal histopathological sections by revealing enlarged dermal papillae containing multiple, bright roundish giant cells, corresponding to foamy histiocytes, and giant cells characterized by a dark center surrounded by a highly hyper-refractile peripheral ring, corresponding to Touton cells. LC-OCT may represent a valid, noninvasive alternative to histopathological examination in clinically atypical cases of xanthogranuloma.

Local ALK-Positive Histiocytosis With Unusual Morphology and Novel TRIM33-ALK Gene Fusion.

ALK-positive histiocytosis was first described in 2008 as a systemic histiocytic disorder involving young infants and neonates. Subsequently, cases of local ALK-positive histiocytosis as well as clinical presentation in adult patients have been increasingly reported in the literature. The current case documented the hitherto largest local ALK-positive histiocytosis lesion involving the mesentery of a 20-year-old female patient, a clinical presentation that has not been previously reported in the medical literature. Of note was the presence of numerous lymphocytes, plasma cells, and eosinophils as well as the formation of lymphoid follicles in the lesion, mimicking an inflammatory myofibroblastic tumor. Other unique histologic aspects of the current case included the nested arrangement of the histiocytes, intravascular extension of the histiocytic proliferation into a large vein, and tumor necrosis. Notably, molecular studies revealed a novel TRIM33 (exon 12)-ALK (exon 20) gene fusion. Therefore, ALK-positive histiocytosis with TRIM33-ALK gene fusion expands the clinical, histologic, and molecular spectrum of local ALK-positive histiocytosis. Since ALK-positive histiocytosis associated with a significant inflammatory component can pose considerable diagnostic challenges, increased awareness of this peculiar variant of ALK-positive histiocytosis is essential to minimize the risk of misdiagnosis.

Hereditary Progressive Mucinous Histiocytosis: New Insights Into a Rare Disease.

Hereditary progressive mucinous histiocytosis is a rare, benign, skin-limited form of non-Langerhans cell histiocytosis. We report on a 5-year-old boy who presented in infancy with self-resolving dermal nodules but later developed persistent and progressive erythematous papules on the face and scalp. Histologic evaluation revealed dermal aggregates of S-100/CD1a-negative histiocytes with abundant mucin. We present this case to highlight the evolution of the lesional morphology in infancy and early childhood and to stress the importance of histology in confirming this rare disorder.

Transplantation in rare lymphoproliferative and histiocytic disorders.

BACKGROUND: Some uncommon lymphoproliferative and histiocytic disorders may present with an aggressive course and require hematopoietic stem cell transplantation (HSCT) as part of the therapeutic approach. METHODS: Published research on the use of HSCT for the treatment of these disorders was reviewed and summarized. RESULTS: Allogeneic HSCT may be indicated in patients with blastic plasmacytoid dendritic cell neoplasia, familial or secondary recurrent hemophagocytic lymphohistiocytosis, and resistant Langerhans cell histiocytosis. Autologous HSCT may be considered in patients with Castleman disease resistant to treatment. No role has been established for the use of HSCT for dendritic cell sarcoma. CONCLUSIONS: HSCT has an evolving role in the treatment of select aggressive lymphoproliferative and histiocytic disorders.

Effective surgical treatment of progressive nodular histiocytosis.

Progressive nodular histiocytosis (PNH) is a rare benign self-limiting histiocytic disorder of the skin that is characterised by the progressive appearance of widespread xanthomatous lesions with no spontaneous remission. We operated on a 13-year-old girl with PNH four times with a result that had stabilised the condition at 1 year.

Successful surgical treatment for pulmonary crystal-storing histiocytosis following the onset of gastric non-hodgkin lymphoma.

Crystal-storing histiocytosis is a rare clinical entity characterized by an increase in the number of abnormal histiocytes accompanied by accumulation of crystallized immunoglobulins. We describe the case of an 80-year-old man who presented with crystal-storing histiocytosis of the lung 13 years after receiving a diagnosis of gastric non-Hodgkin lymphoma (NHL ; clinical stage, Lugano IA). After wedge resection of the left upper lobe, the histological findings showed crystal-storing histiocytosis with CD68(+), some small to medium lymphoid cells with CD79a(+) with κ(+(weekly)) and λ(-), and some plasma cells with CD138(+), and rearrangement of the immunoglobulin heavy chain. Based on the nonrecurrent gastric NHL, small B-cell population, and failure to detect the same clone by polymerase chain reaction analysis, our case was classified as pulmonary localized crystal-storing histiocytosis without underlying lymphoproliferative or plasma cell disorder. The findings of minor B-cell populations harboring a heavy chain rearrangement with slight light-chain restriction (κ > λ) may be related to the pathogenesis of crystallogenesis and crystal-storing histiocytosis. Moreover, surgical treatment may be an effective therapeutic option for solitary crystal-storing histiocytosis.

Crystal-storing histiocytosis as a cause of symptomatic cardiac mass.

Crystal-storing histiocytosis is a rare disorder that is typically associated with low-grade B-cell lymphomas and monoclonal gammopathy. We present a 64-year-old man with a prior history of weakness and weight loss and hematologic evaluation that had revealed immunoglobulin G kappa monoclonal light chains in the serum and negative bone marrow biopsy. He presented with supraventricular tachyarrhythmia and a right atrial mass seen on echocardiogram and excised surgically. Histologically, the tumor was composed of sheets of macrophages infiltrating the atrial myocardium. The histiocytes were filled with multiple needle-shaped, periodic acid-Schiff-negative crystals. These cells and associated plasma cells failed to show clonal light chain restriction by in situ hybridization or immunohistochemistry, and there was no area of lymphoma in the tumor. Ultrastructural examination showed numerous stick-like, trapezoidal, or polygonal dense crystals in the cytoplasm of histiocytes corroborating the diagnosis of crystal-storing histiocytosis. Although rare, crystal-storing histiocytosis should be included in the differential diagnosis of heart masses in patients with hematologic conditions associated with monoclonal gammopathy.

Florid histiocytic hemophagocytosis following therapy with long acting G-CSF (pegfilgrastim).

We describe a case of histiocytic hemophagocytosis and increase in blasts in the bone marrow after administration of long acting G-CSF (pegfilgrastim) in a 71-year-old man with underlying myelodysplasia. Pegfilgrastim was discontinued, with resolution of the hemophagocytosis and marked decrease in blasts from 30 to 5%. We postulate that pegfilgrastim provided a continuous stimulation of the monocyte/macrophage system, resulting in histiocytic hemophagocytosis. We recommend caution in defining indications for the use of long acting preparations of G-CSF.

Intraocular histiocytosis in a 12-year-old girl without systemic disease.

Isolated intraocular histiocytosis is a rare disease that may manifest by recurrent uveitis and solid subretinal masses. The course, diagnosis and treatment of isolated intraocular histiocytosis in a 12-year-old girl are presented. As extensive diagnosis and therapy with corticosteroids and tuberculostatics failed to produce satisfactory results, diagnostic-therapeutic vitrectomy was performed. The intraoperatively obtained material was examined by the methods of histopathology, cytology and immunocytochemistry, along with herpes and cytomegalovirus polymerase chain reaction. The vitreous inflammatory exudate and subretinal masses were operatively removed. Analysis of the intraoperatively obtained material pointed to histiocytosis, whereas additional examinations revealed no systemic manifestations of the disease. Chronic uveitides that respond poorly to classic immunosuppressive therapy require multidisciplinary analysis of intraocular material. Pars plana vitrectomy is an appropriate diagnostic-therapeutic operative procedure.

Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with venous stasis.

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a recently proposed lipomatous entity. HFLL was originally suggested to be a benign reactive lesion arising due to an antecedent trauma. We report two patients with HFLL who also suffered from chronic vein insufficiency due to varicose involving deep veins of the low limbs. Both patients were middle-aged women with solitary, poorly circumscribed subcutaneous lesions on the lower extremities. Histopathological examination revealed typical features of HFLL. We think that the consistent clinical features such as advanced age, female sex predilection, and specific location along with distinctive histopathological features allow the suggestion that impaired blood circulation, to wit, venous stasis is involved in the pathogenesis of HFLL. We hypothesize that the proliferation of spindled fibroblastic and myofibroblastic cells and capillaries, erythrocyte extravasation, and hemosiderin deposition with lipomatous tissue of HFLL may simply represent an exaggerated tissue response to venous stasis in which elevated venous and capillary pressures, oxygen saturation, and edema stimulate the proliferation of the above mentioned elements and lead to erythrocyte extravasation. A similar histopathological pattern is seen in acroangiodermatitis of Mali and vascular transformation of lymph node sinuses, and these conditions are also associated with impaired blood circulation.

Isolated congenital histiocytosis in the palpebral conjunctiva in a newborn.

PURPOSE: To report a rare case of congenital histiocytosis in a newborn without skin involvement. DESIGN: Interventional case-report. METHODS: A full-term baby presented with a mass over the palpebral conjunctiva of his left upper lid. Ophthalmic examination was otherwise normal, and the baby was healthy. There were no skin lesions. RESULTS: The lesion was completely removed surgically. Pathologic examination demonstrated a cellular infiltrate composed of eosinophils and histiocytes. Immunohistochemistry disclosed positive stain for protein S-100 and CD1 antigenic determinant. Pediatric oncology evaluation was completely normal. Eighteen months after presentation, the patient remained healthy without recurrence of the lesion. CONCLUSIONS: Rare cases of congenital histiocytosis can present as a solitary lesion over the palpebral conjunctiva, without skin or systemic involvement.

Laparoscopy in the management of pediatric intraabdominal tumors.

BACKGROUND AND OBJECTIVES: Unresectable intraabdominal tumors pose a challenge to the pediatric oncology team. Tumor tissue is needed for diagnostic and prognostic analyses. Laparotomy is quite invasive and computerized tomography-guided needle biopsies, though less invasive, may not procure enough tissue for a complete analysis. This study aimed to evaluate our experience with laparoscopy in managing these tumors. METHODS: Nine children underwent laparoscopy: 6 for primary tumor biopsy, 2 for tumor resection, and 1 for tumor dissection followed by laparotomy for tumor resection. RESULTS: The study included 7 females and 2 males with a median age of 5 years (range, 3 to 15 years). Three patients had neuroblastoma, 2 had mature ovarian teratomas, 2 had rhabdomyosarcoma, 1 had erythrophagocytic histiocytosis, and 1 had T-cell hepatosplenic lymphoma. In each case, adequate tissue was procured for diagnostic and prognostic analyses. No perioperative complications occurred. Both patients with ovarian teratomas are well. Four patients continue to receive anti-cancer therapy. The patient with erythrophagocytic histiocytosis underwent a cord-blood stem cell transplant. One patient with neuroblastoma was lost to follow-up, and 1 patient with rhabdomyosarcoma died of progressive disease. CONCLUSIONS: Laparoscopy is a valuable technique in the management of pediatric intraabdominal tumors. It allows for tumor biopsy under direct vision, and adequate tissue is procured for all analyses. Moreover, it allows the surgeon to dissect the tumor and determine resectability.

Ocular involvement in a case of systemic indeterminate cell histiocytosis: a case report.

PURPOSE: To describe ocular involvement in a case of systemic indeterminate cell histiocytosis, a rare disease characterized by the proliferation of indistinct histiocytes. These histiocytes resemble Langerhans cells but lack Birbeck granules. The disease usually occurs in adults, with no predisposition for either sex. The clinical features include multiple asymptomatic nodules and cutaneous papules. There are no previous reported cases in the literature regarding ocular indeterminate cell histiocytosis and its treatment. METHODS: A patient with skin papules and hyperpigmentation associated with systemic involvement and corneal infiltration was diagnosed with systemic indeterminate cell histiocytosis after a skin biopsy. Immunohistochemical examination showed specific surface proteins of indeterminate cells, and electron microscopy showed Langerhans-like cells without typical Birbeck granules. Progressive and severe photophobia and corneal thickening made bilateral corneal transplant necessary. RESULTS: Visual acuity remained stable because of the use of systemic immunosuppressors, which decrease the recurrence of infiltration after a corneal transplant. CONCLUSION: Indeterminate cell histiocytosis is a rare disease and there is no previous description of ocular involvement. Infiltrating lesions must be treated with corneal transplant and systemic cyclosporin if they decrease visual acuity.

Tumour surgery of the upper cervical spine--a retrospective study of 13 cases.

A series of tumour cases of the upper cervical spine who we had treated was analysed retrospectively with respect to surgical complications, quality of life and survival, 13 patients (mean age 56 years, metastases 6, plasmocytomas 3, chordomas 2, histiocytosis 1, aneurysmal bone cyst 1) with tumours of the upper cervical spine (C2 n = 7, C2 and C3 n = 4, C3 n = 2) were treated during an 8-year period. A total of 16 operations were carried out with ten one-step procedures and three two step-procedures. Eight extra-oral, one transoral, three dorsal and, in one case, a combined dorsal and extra-oral tumour removal were performed. Four dorsal stabilisation's, four ventral platings and two combined ventral platings plus dorsal fixations and eight vertebral body replacements were carried out. The neurological status and the quality of life were analysed preoperatively and during the follow-up examinations. Flexionextension radiographs were taken during follow-up. There was no operative mortality. The transient morbidity was 8%. The operative intervention significantly improved the quality of life in all patients during the follow-up visits (mean: 20 months). No instability was seen. The average survival time of all patients was 23 months. Six patients died following the operation after a mean time of 28 (4-64) months. Tumour removal in the upper cervical spine using individually modified surgical strategies based on an approach combining tumour location, stabilisation and vertebral body replacement significantly increases the time of survival and quality of life with an acceptable surgical risk for complications.