Neurofibromas are tumors derived from Schwann cells, fibroblasts, and the supporting cells known as perineurial cells. They are benign but may be multiple. When multiple, one must consider the disease of Neurofibromatosis, an inherited disorder.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
DISEASE ASSOCIATIONS CHARACTERIZATION DYSPLASTIC NEVUS
- Dysplastic nevi with an underlying or juxtaposed neurofibroma: does a relationship exist?
Maize Center for Dermatopathology, Charleston, SC, USA.
- J Cutan Pathol. 2007 Nov;34(11):837-43. Abstract quote
Background: Neurofibromas and dysplastic nevi are both common skin disorders found in the general population. The cells in both of these neoplasms are derived from neural crest. There are no published reports of these two lesions occurring in juxtaposition.
Objective: We report, for the first time, three cases of dysplastic nevi in spatial association with a neurofibroma that occurred in unrelated individuals.
Methods and results: Three cases of dysplastic nevi occurring in association with solitary neurofibromas were selected prospectively from the routine accessions from August 1, 2003, to July 31, 2005. In none of the three cases, was a dysplastic nevus suspected by the clinician.
Conclusion: The finding of dysplastic nevi in a spatial relationship to a neurofibroma is not happenstance since they are both of neural crest cell origin and respond to the same growth factors. It is our belief that these lesions are related and may occur together more often than reported.
PATHOGENESIS CHARACTERIZATION APOLIPOPROTEIN D
- Apolipoprotein D is down-regulated during malignant transformation of neurofibromas.
Hunter S, Weiss S, Ou CY, Jaye D, Young A, Wilcox J, Arbiser JL, Monson D, Goldblum J, Nolen JD, Varma V.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hum Pathol. 2005 Sep;36(9):987-93 Abstract quote.
Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry.
Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma.
ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.
CLINICAL VARIANTS CHARACTERIZATION
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS ATYPICAL
Atypical neurofibroma of the skin and subcutaneous tissue: clinicopathologic analysis of 11 cases.
Jokinen CH, Argenyi ZB.
Department of Pathology, University of Washington, Seattle, WA USA.
J Cutan Pathol. 2009 Mar 24. Abstract quote
Background: Neurofibroma (NF) is a relatively common cutaneous tumor, which typically presents little diagnostic difficulty. Occasionally, however, pleomorphic cells may be present in NF raising consideration of other neoplasms like malignant peripheral nerve sheath tumor (MPNST).
Methods: This study examines the clinicopathologic and immunohistochemical features of 11 dermal and subcutaneous 'atypical' NF.
Results: 9/11 (82%) atypical NF were from females, aged 8-70 years. One patient had neurofibromatosis-1. Most presented on the extremities or trunk. The atypical cells had large hyperchromatic, irregular nuclei, and were arranged in a distinct lamellar or fibrillar pattern. Some tumors were hypercellular, but marked density characteristic of MPNST was not observed. All were nonplexiform. Mitoses were mostly absent. The pleomorphic cells expressed S-100 protein. All were negative for p53. MIB-1 was negative in 7/10 (70%) and stained only rare cells in 3 (30%). Epithelial membrane antigen (EMA) and p16 expression were variable. Of six patients with available follow-up, no tumor recurred and none developed malignancy (range 6-63, mean 33 months).
Conclusions: Superficial atypical NF, while morphologically unusual, has no apparent association with neurofibromatosis-1 or short-term risk of recurrence or malignant transformation. Awareness of this variant is important in order to avoid misdiagnosis of a more aggressive neoplasm.
King DT, Barr RJ.
J Cutan Pathol 1980 Feb;7(1):21-31 Abstract quote
Bizarre cutaneous neurofibroma is an uncommon benign neoplasm.
Microscopically, it is usually characterized by stellate and polyhedral cells embedded in a myxoid stroma, and less commonly by solid sheets of epithelioid cells. Cellular pleomorphism and mitotic figures are regular features and have resulted in erroneous diagnosis of malignancy. The mucinous material has the staining characteristics of a sulfated mucosubstance, probably chondroitin sulfate B.
Terms previously applied to this lesion include nerve sheath myxoma. Pacinian neurofibroma, myxoid neurofibroma, and neurotheceoma.
DENDRITIC CELL NEUROFIBROMA WITH PSEUDOROSETTES
- Dendritic Cell Neurofibroma with Pseudorosettes Lacks Mutations in Exons 1-15 of the Neurofibromatosis Type 2 Gene.
Kazakov DV, Vanecek T,
Sima R, Kutzner H, Michal M.
From *Sikl's Department of Pathology, Charles University, Medical Faculty
Czech Republic; and dagger
Dermatohistopathologische Gemeinschaftspraxis, Friedrichshafen, Germany.
Am J Dermatopathol. 2005 Aug;27(4):286-289. Abstract quote
Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a recently proposed variant of neurofibroma with a distinctive microscopic appearance that is produced by a pseudorosette pattern formed by small, dark, lymphocyte-like cells (Type I cells) arranged concentrically around larger cells, with pale-staining vesicular nuclei and copious faintly eosinophilic cytoplasm (Type II cells). Although DCNWPR appears not to be associated with neurofibromatosis (NF), 1 patient with DCNWPR has been described and suggested to have a form of NF because of multiple skin lesions, with 2 of them being DCNWPR as confirmed histologically.
The aim of this study was to find out whether the neurofibromatosis type 2 (NF2) gene is mutated in DCNWPR. Seven histologically proven cases of DCNWPR, from which a substantial amount of archival paraffin-embedded material was available, were selected for this study. Three cases have been previously reported, including the intraneural lesion, and 4 cases were newly identified. There were 3 female and 4 male patients, ranging in age from 30 to 61 years (median, 48 yrs). All patients clinically presented with a small solitary lesion that was clinically diagnosed as fibroma or neurofibroma, and none of the patients had signs of NF.
Follow-up was known for 6 patients (range, 1-5 yrs; median, 2.5 yrs) and was uneventful in each case. Microscopically, all lesions fulfilled the criteria for DCNWPR. Exons 1 to 15 of the NF2 gene were amplified by PCR using primers previously published. The amplified fragments were purified and sequenced. The obtained sequences were computer analyzed and compared with the data of the GenBank database. No mutation was identified in 5 analyzed samples from which suitable DNA had been extracted. DCNWPR appears to have no mutation in exons 1-15 of the NF2 gene.
Given the relatively small number of cases studied, it seems premature to declare that a mutation of the NF2 gene is not involved in DCNWPR, as the possibility cannot be excluded that mutations were present but remained undetected because they occurred in exons that were not examined.
Intraneural dendritic cell neurofibroma with pseudorosettes.
Kazakov DV, Mukensnabl P, Zamecnik M, Michal M.
Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, Pilsen, Czech Republic.
Am J Dermatopathol. 2004 Feb;26(1):72-5. Abstract quote
Dendritic cell neurofibroma with pseudorosettes (DCNWPR) is a recently proposed variant of neurofibroma. However, its peripheral nerve sheath origin has subsequently been questioned, and it has been suggested that the neoplasm could represent a hitherto undescribed variant of melanocytic nevus with neural differentiation.
Here we report a case of DCNWPR that arose almost exclusively within the confinement of the perineurium in the skin. This observation gives further evidence that this entity is a peripheral nerve sheath tumor and is unrelated to melanocytic neoplasms.
Dendritic Cell Neurofibroma With Pseudorosettes A Report of 18 Cases of a Distinct and Hitherto Unrecognized Neurofibroma Variant
Michal Michal, etal.
Am J Surg Pathol 2001;25:587-594 Abstract quote
The authors present 18 cases of a hitherto unrecognized variant of cutaneous neurofibroma.
The tumors presented in adults (10 occurred in men and eight occurred in women) as a solitary, well-circumscribed, superficial lesion located in the dermis measuring 3 to 17 mm (mean size, 6.2 mm).
The tumors formed oval-shaped masses that ran perpendicular to the epidermis. In the deep part of the tumor there was multinodular arrangement with two types of cells: Type I cells were small, dark, lymphocyte-like cells with a slightly irregular nucleus and inconspicuous cytoplasm. Type II cells were larger, with pale-staining vesicular nuclei, with frequent invaginations and intranuclear inclusions, and had copious clear eosinophilic cytoplasm that formed a stellate growth pattern, which was poorly visible on hematoxylin and eosin staining. Type I cells were grouped concentrically around type II cells and formed pseudorosettes.
Most of the type I and type II cells were S-100 protein and CD57 positive, and various proportions of both cell types were CD56 and PGP9.5 positive. All cells were chromogranin A, synaptophysin, glial fibrillary acidic protein, cytokeratins, CD1a, CD21, CD31, -smooth muscle actin, muscle-specific actin, desmin, and HMB-45 negative. CD34 stained intralesional fibroblasts. Antibody to epithelial membrane antigen stained only the perineurium around the tumor masses, suggesting that the tumors arose inside the nerve sheath. No signs of neurosecretory granules were present at ultrastructural level.
None of the lesions recurred and none metastasized over a mean follow-up of 8.1 years.
- Benign Epithelioid
Peripheral Nerve Sheath Tumors of the Soft
Tissues: Clinicopathologic Spectrum of 33 Cases.
Laskin WB, Fetsch JF, Lasota J, Miettinen M.
From the *Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL; and the daggerDepartment of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC.
Am J Surg Pathol. 2005 Jan;29(1):39-51. Abstract quote
Benign epithelioid peripheral nerve sheath tumors (BEPNSTs) have not been fully characterized, and their relationship to conventional schwannoma and neurofibroma has not been satisfactorily established.
Herein, we detail the clinicopathologic features of 33 examples of BEPNST. The study included 22 females and 11 males ranging in age from 2 to 68 years (median, 31.5 years). Only one patient probably has neurofibromatosis type 1. The tumors were predominantly dermal/subcutaneous in location (85%) and involved the lower limb (n = 15), upper limb (n = 11), trunk (n = 4), and head/neck (n = 3). The lesions ranged in size from 0.3 to 6.8 cm (median, 1.1 cm).
Microscopically, the tumors were generally well-circumscribed, uninodular, or multinodular masses. Twenty-six lesions were encapsulated. Tumors consisted of trabeculae, loosely arranged nodules, and cohesive nests of epithelioid tumor cells immersed in collagenous, myxohyaline, or chiefly myxoid stroma. A bland spindled cell component comprising 5% to 40% of the tumor was noted in 15 cases. Mitotic activity ranged from 0 to 6 mitoses/50 high power fields (mean, 1.5 mitoses/50 high power fields) with no abnormal division figures identified. Five lesions were considered atypical based on presence of focal nuclear/nucleolar enlargement and hyperchromasia. Immunohistochemical reactivity for Schwann cell-related markers in tumor cells included S-100 protein (20 of 20 cases), collagen type IV (10 of 10), laminin (8 of 8), nerve growth factor receptor, p75(7 of 8), CD57 (6 of 9), and glial fibrillary acidic protein (8 of 15). CD34-positive fibroblast-like cells were identified in all 12 neoplasms tested. Anti-epithelial membrane antigen highlighted perineurial cells in 9 of the 11 encapsulated tumors. Anti-neurofilament protein did not identify intralesional neuraxons in the 10 tumors evaluated. Eighteen tumors were subtyped as epithelioid neurofibromas. The remaining 15 cases showed some histologic features suggestive of schwannoma, but their uniform cellularity, absence of nuclear palisading, and presence of a significant CD34-positive spindled cell population in 5 cases led to their classification as "BEPNST of indeterminate histogenesis."
Evaluation for loss of heterozygosity in 2 cases demonstrated deletion of genetic material on chromosome 22q and 17q involving NF2 and NF1 loci. However, sequencing of NF2 coding sequences revealed no mutations. Follow-up for 18 patients (median interval, 13.5 years), including 4 patients with tumors exhibiting cytologic atypia, revealed a nondestructive recurrence or persistent disease in 3 patients whose tumors lacked atypia, but no evidence of metastatic spread or tumor-related death.
BEPNSTs are usually small neoplasms located in superficial soft tissue and have an excellent prognosis after complete local excision. Accurate subclassification of some of these lesions is difficult based on currently available techniques.
Am J Surg Pathol. 2006 Mar;30(3):337-44. Abstract quote
Benign nerve sheath tumors of soft tissue can occasionally adopt unusual or unfamiliar morphologic appearances that may introduce difficulties for diagnosis, such as multinucleation, bizarre nuclei, intranuclear vacuoles, and other degenerative changes. Tumor cells adopting a signet-ring or lipoblast-like configuration, however, are mostly associated with epithelial malignancies, liposarcoma and melanoma, and have been only rarely observed in spindle cell tumors of soft tissue.
We report 5 cases of benign nerve sheath neoplasms that displayed prominent signet-ring cells with lipoblast-like features. The cases presented as solitary soft tissue masses in the groin, thigh, retroperitoneum, and shoulder in 4 men and 1 woman between the ages of 31 to 57 years. Four tumors predominantly showed features of schwannoma and one of neurofibroma; however, intimately admixed with the spindle cell population, there were also numerous scattered mature adipocytes as well as lipoblast-like cells displaying a signet-ring cell appearance. Immunohistochemical studies showed strong S-100 protein positivity in the spindle cells as well as in the signet-ring lipoblast-like cells and the mature adipocytes.
The signet-ring cells were negative for mucin stains, cytokeratin, EMA, CEA, and several other differentiation markers. Ultrastructural examination was performed in 2 cases. The signet-ring cells contained large cytoplasmic lipid droplets that displaced the nuclei to the periphery, consistent with lipoblastic differentiation, whereas complex, interdigitating cytoplasmic processes covered by basal lamina material characteristic of nerve sheath differentiation could be identified in the spindle cells. Four patients for whom follow-up was available were alive and well with no evidence of recurrence over a period of 28 to 116 months (median follow-up, 50 months).
The presence of mature fat and signet-ring lipoblast-like cells within a nerve sheath neoplasm is quite rare and may signify a process of aberrant differentiation. Neurogenic tumors should be added in the differential diagnosis of spindle cell tumors capable of displaying prominent signet-ring cell features.
- Cutaneous lipomatous neurofibroma: characterization and frequency.
Val-Bernal JF, Gonzalez-Vela MC.
Department of Anatomical Pathology, Marques de Valdecilla University Hospital, University of Cantabria, Santander, Spain.
J Cutan Pathol. 2005 Apr;32(4):274-9. Abstract quote
Background: There are numerous variants of cutaneous neurofibroma reflecting its manner of growth and histologic composition. Lipomatous neurofibroma is the latest described variant with only eight cases reported.
Methods: A systematic study based on 320 consecutive specimens diagnosed of cutaneous neurofibroma was carried out. Conventional microscopy, immunohistochemistry, and statistical methods were used to determine the presence of fat cells, their amount, distribution, and frequency.
Results: Intratumoral fat was observed in 22 (6.9%) neurofibromas. All these were dermal neurofibromas. Intraneoplastic fat was divided into two groups: focal and diffuse (regularly interspersed). Eighteen tumors (5.6%) presented adipocytes focally intermingled with the spindle cells. There were four (1.3%) neurofibromas showing spindle cell proliferation with regularly scattered adipocytes. Lipomatous neurofibroma was more frequent located on head and neck than non-lipomatous neurofibroma ( p = 0.04). Neurofibromas without mature adipocytes were more frequently immunoreactive for CD34 compared with tumors showing intratumoral fat ( p = 0.02).
Conclusions: We suggest that both metaplasia and aberrant adipose differentiation from multipotential cells may result in lipomatous neurofibroma. Focal presence of adipose cells may be attributable to metaplasia as the pathogenic mechanism. The fatty tissue being intrinsic to the tumor structure in its diffuse form, the lesion represents a distinctive tumor of the peripheral nerve sheath.
Cutaneous Lipomatous Neurofibroma
J. Fernando Val-Bernal, M.D.; José de la Dehesa, M.D.; M. Francisca Garijo, M.D.; Daniel Val, M.D.
Am J Dermatopathol 2002; 24(3):246-250 Abstract quote
We report a cutaneous lipomatous neurofibroma on the skin of the left-side parietal area of approximately 9 months' duration in a 67-year-old woman. The regular distribution of adipose tissue throughout the lesion suggested that fat was an integral part of the tumor, not a metaplastic or degenerative process. To our knowledge, this type of lesion has not been documented.
The main differential diagnosis embraces neurocristic cutaneous hamartoma, lipoma and its variants, cutaneous meningioma, and neural nevus with fat replacement. We propose that lipomatous neurofibroma of the skin is caused by aberrant development of adipose tissue in a neurofibroma. The lesion originated as pluripotential neural crest cells after migration. This acquired lesion could arise from local stem cells. The old suggestion that neuroectoderm is capable of mesenchymal differentiation may be relevant to the histogenesis of this neoplasm.
Intratumoral fat in neurofibroma.
Ahn SK, Ahn HJ, Kim TH, Hwang SM, Choi EH, Lee SH.
Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea; and the Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea.
Am J Dermatopathol 2002 Aug;24(4):326-9 Abstract quote
Three cases of a solitary neurofibroma showing focal fatty changes are reported. Fatty changes in a neurofibroma are rarely observed and have not been reported, and also, the pathogenesis of neurofibroma has not been clarified.
We postulate that the fatty changes in a neurofibroma may be the result of so-called senescent change or chronic injury. The origin of adipose cells may be attributable to fatty infiltration from abutting tissues or to a metaplasia of tumor cells or resident fibroblasts.
OCCULT NEUROFIBROMA Occult neurofibroma and increased S-100 protein in the skin of patients with neurofibromatosis type I
Arch Dermatol 2000;136:1207-1209
Histologic examination of healthy looking skin revealed a small neurofibroma in 1/10 pts
In 4/10 pts, there was abundant S100 positive staining cells within the matrix surrounding hair follicles and 7/10 had increased fibroblasts around the hair follicles
Suggests that very early neurofibromas are predominately fibroblasts suggesting these cells mediate the initial response to trauma and contribute to the size of the mass
PIGMENTED Pigmented neurofibroma: review of Japanese patients with an analysis of melanogenesis demonstrating coexpression of c-met protooncogene and microphthalmia-associated transcription factor.
Motoi T, Ishida T, Kawato A, Motoi N, Fukayama M.
Department of Pathology, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
Hum Pathol. 2005 Aug;36(8):871-7. Abstract quote
Pigmented neurofibroma (PNF) is a rare variant of neurofibroma showing melanin production.
To clarify the clinicopathologic features of PNF and to characterize melanogenesis in PNF, 12 cases of PNF were examined in comparison with schwannoma (SCH, n = 16) and neurofibroma (NF, n = 26). The PNF patients were all Japanese including 7 men and 5 women, and patient age ranged from 11 to 71 years (median, 23.5 years). They showed strong a predisposition for neurofibromatosis type 1. Their tumor size was large, and tumors arose from various sites of skin.
Histologically, clusters of epithelioid, dendritic, and spindle melanin-producing cells with faint pigmentation had a tendency to locate in deep dermis and subcutis, which seems to be a characteristic pattern of melanogenesis. There was a transition between melanin-producing cells and Schwann cells.
Immunohistochemical examination included known melanogenic markers, microphthalmia-associated transcription factor (MITF), which is a key regulator of melanogenesis, and 2 tyrosine kinase receptors, c-Met and c-Kit, which regulate the development of melanocytes. In PNF, melanin-producing cells were S100 (+), MITF (+), Melan-A (+), tyrosinase (+/-), HMB45 (+/-), c-Met (+), and c-Kit (-). Schwann cells were S100 (+), MITF (-), Melan-A (-), tyrosinase (-), HMB45 (-), c-Met (-), and c-Kit (-), and intermediate spindle cells were S100 (+), MITF (+), Melan-A (+), tyrosinase (-), HMB45 (-), c-Met (+), and c-Kit (-). When compared with SCH and NF, MITF was weakly expressed in a part of tumor cells of SCH, whereas no definite staining was found in NF. c-Met expression was very weak in a scattered manner in SCH (10/15 cases) and NF (10/26 cases). These results suggest that PNF is a unique tumor that shows differentiation toward mature melanin production, but ability of melanin synthesis seems to be impaired.
There may be a close relationship between up-regulated MITF and c-Met and the peculiar melanogenic nature of PNF, and both of these are useful diagnostic tools for distinguishing PNFs with less melanin production from NFs.
Pigmented (Melanotic) Neurofibroma A Clinicopathologic and Immunohistochemical Analysis of 19 Lesions From 17 Patients
John F. Fetsch, M.D.; Michal Michal, M.D.; Markku Miettinen, M.D.
From the Department of Soft Tissue Pathology (J.F.F., M.M.), Armed Forces Institute of Pathology, Washington, DC; and the Department of Pathology (M. Michal), Faculty Hospital, Pilsen, Czech Republic.
Am J Surg Pathol 2000;24:331-343 Abstract quote
Neurofibromas with melanin-laden pigmented cells are rare, accounting for less than 1% of all neurofibromas accessioned to the Soft Tissue Registry of the Armed Forces Institute of Pathology between the years 1970 and 1996.
This study analyzes the clinicopathologic features associated with 19 specimens removed from 17 patients. Eleven males and six females, ranging in age from 2 to 61 years (median, 28 years), participated in the study. Nine of 15 patients whose race was provided were black. Eight patients (47%) are known to have neurofibromatosis, and two others (12%) are strongly suspected of having this disorder; two patients have similarly affected family members. Eight patients were noted to have multiple skin tumors, and in each of two cases, two pigmented neurofibromas were available for review. Two patients had hypertrichosis and cutaneous hyperpigmentation resembling a hairy nevus, and one had a café au lait spot directly overlying a pigmented neurofibroma. Tumors ranged in size from 1.7 to 50 cm in greatest dimension and involved the buttock or leg (n = 6), head or neck (n = 8), trunk (n = 2), wrist or hand (n = 2), and an unspecified site (n = 1).
The neurofibromas exhibited diffuse (n = 15), combined diffuse and plexiform (n = 2), combined diffuse and intraneural epithelioid (n = 1), and nonspecific (n = 1) growth patterns. The process involved the skin (n = 14), subcutis (n = 18), and/or skeletal muscle (n = 3). Wagner–Meissner-like bodies were identified in 11 tumors, and mitoses (average, less than one mitosis per 10 high-power fields) were present in three lesions. All examples contained scattered pigmented cells with dendritic, tadpole-shaped, spindled or epithelioid morphology.
These cells were positive with Fontana–Masson (nine of nine) and Warthin–Starry (pH, 3.2; four of four) stains, and were depigmented with a melanin bleach method (two of two). An iron stain was negative. The tumors had immunoreactivity for S-100 protein (11 of 11), HMB-45 (10 of 11), Melan-A (four of four), tyrosinase (four of four), and CD34 (four of four). Although recurrences are documented, none of the tumors are known to have undergone malignant transformation.
A pigmented neurofibroma can be confused with a pigmented dermatofibrosarcoma protuberans (Bednár tumor) because the melanin-laden cells of both processes are similar. However, the latter entity exhibits a more extensive storiform growth, has greater immunoreactivity for CD34, and lacks a diffuse proliferation of S-100 protein-positive Schwann cells.
J Cutan Pathol. 2006 Jan;33(1):47-50. Abstract quote
Background: Neurofibroma (NF) is a benign tumor of the nerve sheath. Several variants of NF have been described.
Purpose: We report a case of NF with sclerotic changes resembling sclerotic fibroma (SF).
Methods and Results: The patient was a 61-year-old man who had an asymptomatic cutaneous lesion on the right scapular region. Physical examination revealed a pedunculated, white-to-pinkish nodule that had a firm consistency, spherical morphology, and smooth surface. Microscopically, the nodule showed a well-circumscribed, nonencapsulated dermal tumor composed of scant cells and thick collagen bundles with prominent clefts. The tumor cells were immunoreactive for vimentin and S100 protein. The patient was diagnosed as having pure sclerotic NF. To our knowledge, only five cases of NF with SF-like pattern have been previously published, and in two this pattern was pure.
Conclusion: It is important to recognize this exceptional type of NF because it may be easily confused with SF, as well as with a wide variety of neoplasms or hamartomatous conditions containing similar sclerotic pattern.
- Vacuolated cells in neurofibroma: an immunohistochemical study.
Department of Pathology, Kariya General Hospital, Kariya, Aichi, Japan.
J Cutan Pathol. 2005 Feb;32(2):158-61. Abstract quote
Background: Vacuolated cells could be encountered in neurofibroma.
Objectives: Frequency and immunohistochemical feature of vacuolated cells in neurofibroma.
Methods: Sixty-two lesions of neurofibroma including five plexiform neurofibromas were re-evaluated for the search of vacuolated cells. Immunohistochemical analysis was performed for cases with vacuolated cells.
Results: In five cases of plexiform neurofibroma and four cases of sporadic neurofibroma with endoneurial component, presence of vacuolated cells in the endoneurial mucoid area was noted. They were immunoreactive both with S-100 protein and CD34, mostly negative for factor XIIIa and negative for epithelial membrane antigen. Vacuolated cells were found neither in the diffuse portion of plexiform neurofibroma nor in sporadic diffuse neurofibroma.
Conclusion: Presence of vacuolated cells is a highly characteristic feature of endoneurial portion of neurofibroma. Considering immunoreactivity both with S-100 protein and CD34 in the majority of vacuolated cells, they could be regarded as to represent endoneurial precursor cells in a certain stage of differentiation to Schwann cells.
CHARACTERIZATION Special stains S100 positive
DIFFERENTIAL DIAGNOSIS GANGLIONEUROMA
Primary cutaneous ganglioneuroma: a report of two cases and literature review.
Wallace CA, Hallman JR, Sangueza OP.
Am J Dermatopathol. 2003 Jun;25(3):239-42. Abstract quote
Primary cutaneous ganglioneuroma is a rare neoplasm first described by Collins et al. in 1972. Eight cases have been reported in the English literature to date.
We report two cases of solitary cutaneous ganglioneuroma, one constituting, to our knowledge, the first reported case of this entity occurring on the face. Clinically, both lesions were firm flesh-colored papules and asymptomatic, being removed primarily for cosmesis. Neither patient had any significant past medical history.
Histologically, both neoplasms consisted of relatively well-circumscribed spindle cell proliferations of axons and Schwann cells with interspersed mature ganglion cells. There was also focal myxoid change. The spindle cell component stained positively for S-100 protein, and the ganglion cells stained positively for glial fibrillary acidic protein and neurofilaments by routine immunohistochemistry.
PROGNOSIS AND TREATMENT CHARACTERIZATION
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