Differences and diversity of autoimmune encephalitis in 77 cases from a single tertiary care center.

BACKGROUND: The incidence of autoimmune encephalitis has risen globally. There are two general categories of disease-associated antibodies that can be tested for: neuronal surface and intracellular. However, testing both groups of autoantibodies are costly. This study aims to identify differences between groups by comparing clinical presentations, radiological findings and CSF profile of patients, and determine if any parameters are indicative of one group of autoantibodies over another. Additionally, we aim to report the local incidence of less common groups of disease-associated antibodies as well. METHODS: Seventy-seven records of autoimmune encephalitis/encephalomyelitis patients admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between October 2010 and February 2017 were reviewed. Patients with infections or those with classic central nervous system demyelinating features were excluded. RESULTS: Of 77 patients, 40% presented with neuronal surface antibodies and 33% had intracellular antibodies. The most common autoantibody detected in each group was anti-NMDAr antibody (25/31, 81%) and anti-Ri antibody (7/25, 28%) respectively. In the neuronal surface antibody group, behavioral change was the most common complaint (45%), followed by seizures (39%) and abnormal movements (29%). In the latter group, seizure was the most common presenting symptom (32%), followed by motor weakness (20%), behavioural change (16%) and abnormal movements (16%). Patients with neuronal surface antibodies were younger (35 vs 48 years old, p = 0.04) and more likely to present with behavioral change (45% vs 16%, p = 0.02). Mortality rate was higher in the intracellular group (16% vs 3.2%, p = 0.09). No differences were detected in magnetic resonance imaging (MRI) and CSF profile. CONCLUSIONS: In the early stages of the disease, both groups have comparable clinical outcomes. Although there were significant differences in age and percentage of patients with behavioral change, both groups of autoimmune encephalitis still shared many clinical features and could not be distinguished based on MRI and CSF profiles. Therefore, we recommend that patients with features of autoimmune encephalitis should be screened for both the neuronal surface and intracellular antibodies regardless of clinical presentation.

[Autoimmune encephalitis. Anti-NMDA receptor and new immunophenotypes]. / Encefalitis autoinmunes. Receptor anti-NMDA y nuevos inmunofenotipos.

Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

Encefalitis autoinmunes: Receptor anti-NMDA y nuevos inmunofenotipos / Autoimmune encephalitis. Anti-NMDA receptor and new immunophenotypes

Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

The association between thyroid echogenicity and thyroid function in pediatric and adolescent Hashimoto's thyroiditis.

In this study, we evaluated the association between thyroid echogenicity on ultrasonography (US) and thyroid function in pediatric and adolescent Hashimoto's thyroiditis (HT) patients.In 86 pediatric and adolescent HT patients, the association between echogenicity and thyroid function and microsomal autoantibody status was evaluated. Among patients with overt hypothyroidism, 89.2% (33/37) showed a US grade of 3 or 4. All of the patients at grade 4 presented with overt hypothyroidism. In contrast, 97.8% (44/49) of the patients with subclinical hypothyroidism or euthyroidism showed grades 1 or 2. Patients with increased thyroid-stimulating hormone titer also tended to have increased US grades (P < .001). In contrast, free thyroxine levels were significantly decreased with increasing US grade (P < .001).In conclusion, patients with higher US grades had decreased thyroid function (P < .001).

[Autoimmune encephalitis. A review]. / Encefalitis autoinmunes: criterios diagnósticos y pautas terapéuticas.

Autoimmune encephalitis are one of the emergent causes of subacute changes in the level of consciousness, behavior, cognitive impairment and seizures, mainly in young people. They are a consequence of inflammation or dysfunction of parts of the brain caused by antibodies against specific brain antigens, usually located in the limbic system, resulting in clinical presentation as a limbic encephalitis. The objectives of this article are to show the clinical presentation, complementary studies and treatment of this entity, considering that the patient's prognostic depends on a high level of clinical suspicion, and on an early initiation of immunosuppressive therapy. We did a nonsystematic review of the literature on autoimmune encephalitis between 2005 and 2017. We conclude that the prevalence of autoimmune encephalitis is increasing, even surpassing infectious causes of encephalitis in developed countries. Clinical presentation includes sub-acute cognitive and behavioral impairment, with or without alterations in consciousness and seizures. Fever and inflammation of the cerebrospinal fluid are less common than in the infectious causes but psychiatric symptoms are more frequent. There are specific clinical presentations according to the particular type of antigen/antibody present, which also determines the association with cancer, constituting a paraneoplastic syndrome only in some cases. Immunosuppressive therapy has been standardized in steps, and should be initiated early to improve prognosis.

Encefalitis autoinmunes: criterios diagnósticos y pautas terapéuticas / Autoimmune encephalitis. a review

Autoimmune encephalitis are one of the emergent causes of subacute changes in the level of consciousness, behavior, cognitive impairment and seizures, mainly in young people. They are a consequence of inflammation or dysfunction of parts of the brain caused by antibodies against specific brain antigens, usually located in the limbic system, resulting in clinical presentation as a limbic encephalitis. The objectives of this article are to show the clinical presentation, complementary studies and treatment of this entity, considering that the patient's prognostic depends on a high level of clinical suspicion, and on an early initiation of immunosuppressive therapy. We did a nonsystematic review of the literature on autoimmune encephalitis between 2005 and 2017. We conclude that the prevalence of autoimmune encephalitis is increasing, even surpassing infectious causes of encephalitis in developed countries. Clinical presentation includes sub-acute cognitive and behavioral impairment, with or without alterations in consciousness and seizures. Fever and inflammation of the cerebrospinal fluid are less common than in the infectious causes but psychiatric symptoms are more frequent. There are specific clinical presentations according to the particular type of antigen/antibody present, which also determines the association with cancer, constituting a paraneoplastic syndrome only in some cases. Immunosuppressive therapy has been standardized in steps, and should be initiated early to improve prognosis.

A Controversial New Approach to Address Hematological Parameters in Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common autoimmune disorder. Genetic, environmental, and immunological factors all play a role in the pathogenesis of HT, but the effects of lymphocytes and platelets on the pathophysiology of HT are still unknown. In this study, we evaluated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in HT groups and HT subgroups with low cardiovascular risks. METHODS: This study included 92 patients with HT and 38 control subjects. Among the HT patients, three subgroups were formed according to thyroid function: overt (n = 12), subclinical (n = 38), and euthyroid (normally functioning thyroid; n = 42). RESULTS: Age and gender distributions were similar between the patient and control groups. Body mass index was higher in the patient group than in the control group. The C reactive protein level was higher in patients than controls (p = 0.064). The thyroid stimulating hormone (TSH) level was higher and the mean free thyroxine level lower in the patient group than in the control group (p < 0.05). There were no differences between the groups with regard to leukocytes, neutrophils, platelets, or MPV (p > 0.05). The NLR and PLR were significantly different in one subgroup of HT patients relative to healthy subjects (p < 0.05). However, we did not find any statistical differences in the MPV among the three subgroups (p = 0.547). A positive correlation was found among the NLR, anti-thyroglobulin (TG) antibodies, and anti-thyroid peroxidase (TPO) antibodies (p < 0.01), although there was a negative correlation between the PLR, TSH, anti-TPO, and anti-TG (p < 0.001). CONCLUSIONS: A single marker or panel of biomarkers is not a consistent indicator of HT, but NLR combined with PLR testing may offer a more reliable diagnosis.

The diagnostic accuracy of fine-needle cytology of Hurthle cell lesions; A comprehensive cytological, clinical and ultrasonographic experience.

BACKGROUND: Fine-needle cytology (FNC) diagnosis and pre-operative classification of Hurthle cells (HC) lesions may be difficult. Rapid on-site evaluation (ROSE) enhances the efficiency of FNC, mainly when utilized in close combination to clinical and ultrasound (US) data. OBJECTIVE: to describe an experience on HC FNC with contextual clinical,US and ROSE evaluation and assess if this comprehensive approach improves the FNC accuracy of HC lesions. METHODS: FNC of 112 HC lesion were diagnosed and classified, according to the Bethesda system, by clinical, US and ROSE in one year. All the cases were controlled by follow-up and histology when performed. RESULTS: Eighty-five cases were diagnosed HC rich goiter or Hashimoto thyroiditis and were classified THY2; 5 cases were diagnosed hyperplastic nodular goiter and classified THY3A. Eight cases were diagnosed suspect neoplasia and classified THY3B. Two cases were diagnosed suspect HC papillary thyroid carcinoma (PTC) and classified THY4 and 2 cases were diagnosed HC-PTC and classified THY5. THY3B, THY4, THY5 and 1 THY3A were histologically controlled. FNC were confirmed in 14 out of the 17 THY3-THY5 cases. CONCLUSIONS: A comprehensive diagnostic approach that include FNC, clinical data, US and ROSE improves the diagnosis and classification of HC lesions.

Cognitive and affective dysfunctions in autoimmune thyroiditis.

Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits.

A classification of Hashimoto's thyroiditis based on immunohistochemistry for IgG4 and IgG.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common organ-specific autoimmune disease. Antithyroglobulin antibodies (TgAb) and antithyroperoxidase antibodies (TPOAb), predominantly of the immunoglobulin (Ig) G class, are hallmarks of HT. It has been reported that HT can be divided into IgG4 and non-IgG4 thyroiditis. The aim of our study was to investigate the meaning of this classification. METHODS: Thyroid sections from 53 Hashimoto's patients with stored serum samples were collected to detect IgG4, IgG, α-smooth muscle actin, and transforming growth factor-ß1 expression by immunohistochemical staining. The degree of fibrosis of thyroid parenchyma was qualitatively evaluated by Masson's trichrome. Serum total IgG, IgG4, TPOAb IgG, TgAb IgG, TPOAb IgG4, and TgAb IgG4 were detected by enzyme-linked immunosorbent assays (ELISAs). RESULTS: Based on immunohistochemistry for IgG4 and IgG, 12 cases of IgG4-positive HT and 41 cases of IgG4-negative HT were identified in our study. The patients in the IgG4-positive HT group were significantly younger than those in the IgG4-negative HT group (p=0.023), and no significant differences were found in sex distribution, disease duration, and distribution of thyroid functional status between these two groups. The degree of fibrosis evaluated by Masson's trichrome and the immunohistochemical expression score of TGF-ß1 in the IgG4-positive HT were significantly higher than those in the IgG4-negative HT (p<0.05). No significant differences were found in the levels of serum IgG4, total IgG, or IgG4/IgG ratio. However, TPOAb IgG4 and TgAb IgG4 levels and the ratios of TPOAb IgG4/TPOAb IgG, TgAb IgG4/TgAb IgG, TPOAb IgG4/IgG4, and TgAb IgG4/IgG4 were significantly higher in the IgG4-positive HT group than those in the IgG4-negative HT group respectively (p<0.05). CONCLUSIONS: Our study indicates that HT can be divided into IgG4-positive and IgG4-negative HT, and this classification might have important clinical implications. The levels of IgG4 binding to specific thyroid antigens might be noninvasive markers to differentiate these two different immunophenotypes.

The role of the resistive index in Hashimoto's thyroiditis: a sonographic pilot study in children.

OBJECTIVE: The role of Doppler ultrasonography in the diagnosis of diffuse thyroid diseases is not well established. In particular, Doppler ultrasonography findings in children with Hashimoto's thyroiditis are very limited. We examined gray-scale and Doppler ultrasound findings in Hashimoto's thyroiditis in children in an attempt to understand the feasibility of future prospective controlled studies. MATERIALS AND METHODS: Twenty-one children with newly diagnosed Hashimoto's thyroiditis were recruited in the study. The patients were euthyroid or had subclinical hypothyroidism at the time of the ultrasonography examination. According to the color Doppler scale developed by Schulz et al., thyroid glands were classified into four patterns based on visual scoring and the mean resistive index (RI), which was calculated via measurements from both lobes, and these results were compared with gray-scale findings. RESULTS: The mean RI value, calculated as the mean of the RI values of both lobes obtained from each patient, was found to be 0.57 ± 0.05 (range 0.48-0.67) cm/sn. The distribution of thyroid classifications was as follows: Pattern 0, n = 7; Pattern I, n = 6; Pattern II, n = 4; and Pattern III ("thyroid inferno"), n = 4. The mean RI values in patients with normal or near-normal gray-scale findings (n = 10) and patients with more substantial gray-scale changes (n = 11) were not significantly different and were lower than the values in normal children previously presented in the literature. CONCLUSION: The results indicated that the RI may be more sensitive than other ultrasound parameters for the diagnosis of Hashimoto's thyroiditis.

The role of the resistive index in Hashimoto's thyroiditis: a Sonographic pilot study in children

OBJECTIVE: The role of Doppler ultrasonography in the diagnosis of diffuse thyroid diseases is not well established. In particular, Doppler ultrasonography findings in children with Hashimoto's thyroiditis are very limited. We examined gray-scale and Doppler ultrasound findings in Hashimoto's thyroiditis in children in an attempt to understand the feasibility of future prospective controlled studies. MATERIALS AND METHODS: Twenty-one children with newly diagnosed Hashimoto's thyroiditis were recruited in the study. The patients were euthyroid or had subclinical hypothyroidism at the time of the ultrasonography examination. According to the color Doppler scale developed by Schulz et al., thyroid glands were classified into four patterns based on visual scoring and the mean resistive index (RI), which was calculated via measurements from both lobes, and these results were compared with gray-scale findings. RESULTS: The mean RI value, calculated as the mean of the RI values of both lobes obtained from each patient, was found to be 0.57 ± 0.05 (range 0.48-0.67) cm/sn. The distribution of thyroid classifications was as follows: Pattern 0, n = 7; Pattern I, n = 6; Pattern II, n = 4; and Pattern III ("thyroid inferno"), n = 4. The mean RI values in patients with normal or near-normal gray-scale findings (n = 10) and patients with more substantial gray-scale changes (n = 11) were not significantly different and were lower than the values in normal children previously presented in the literature. CONCLUSION: The results indicated that the RI may be more sensitive than other ultrasound parameters for the diagnosis of Hashimoto's thyroiditis.

Reclassifying formerly indeterminate thyroid FNAs using the Bethesda system reduces the number of inconclusive cases.

OBJECTIVE: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. STUDY DESIGN: According to the BSRTC, we reclassified cytologic samples originally diagnosed as 'indeterminate' with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as 'atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)'. RESULTS: According to the BSRTC, 154 'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused inconclusive diagnoses. CONCLUSION: The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto's thyroiditis precluded cytopathologists from making definitive diagnoses.

Immunohistochemistry of IgG4 can help subclassify Hashimoto's autoimmune thyroiditis.

IgG4-related sclerosing disease has been recently recognized as a systemic disease entity characterized by an elevated serum IgG4 level, sclerosing fibrosis and diffuse lymphoplasmacytic infiltration by many IgG4-positive plasma cells. Similar histopathological features have often been noted in the fibrous variant of Hashimoto's autoimmune thyroiditis, but thyroid gland involvement has been only briefly mentioned with regard to IgG4, and no immunohistochemistry for IgG4 has been reported in Hashimoto's autoimmune thyroiditis. Herein, the purpose of the present study was to investigate the infiltration of IgG- and IgG4-positive plasma cells on immunohistochemistry for a panel of thyroiditis samples (Hashimoto's autoimmune thyroiditis, n= 13; subacute thyroiditis, n= 2; lymphocytic thyroiditis, n= 2). Cases of Hashimoto's thyroiditis could be classified into two groups based on immunostaining of IgG4: IgG4 thyroiditis (IgG4-related, IgG4-positive plasma cell-rich thyroiditis) and non-IgG4 thyroiditis (non-IgG4-related, IgG4-positive plasma cell-poor thyroiditis). IgG4 thyroiditis presents with severe lymphoplasmacytic infiltration, dense fibrosis, marked follicular cell degeneration, oxyphilic change and lymphoid follicle formation, while non-IgG4 thyroiditis presents with relatively mild or absent histopathological characteristics. In conclusion, immunostaining of IgG4 can help subclassify Hashimoto's thyroiditis; and IgG4 thyroiditis may have a close relationship with IgG4-related sclerosing disease.

[What diagnosis can be made by the pathologist in a case of sclerosing thyroiditis?]. / Quel diagnostic l'anatomopathologiste peut-il porter en présence d'une thyroïdite sclérosante ?

The pathology of thyroiditis seems well-established with a recognized classification based on clinical and pathological features. However, problems of differential diagnosis remain between both Riedel's and Quervain's thyroiditis and sclerosing Hashimoto's thyroiditis: these entities sometimes lack the characteristic histological pattern, and the clinico-biological data are not always available to the pathologist. We re-examined 18 cases of thyroiditis with sclerosis, retrieved from our files, diagnosed as Riedel's thyroiditis in five cases, Quervain's thyroiditis in five other cases and sclerosing Hashimoto thyroiditis in eight cases. Only two diagnosed cases of Riedel's thyroiditis were pathognomic. Three cases of Quervain's thyroiditis and four cases of sclerosing Hashimoto's thyroiditis presented a slight or moderate extension of the fibrosis in perithyroidal soft-tissues, raising the differential diagnosis of an incipient Riedel's thyroiditis. A definite diagnosis of the type of thyroiditis with sclerosis remains difficult, because all three pathologies present common points. In cases with a characteristic pattern, the diagnosis is straightforward. However, it appears in our study that half of the diagnoses remain ambiguous, because of the existence of histological features common to different entities. In these cases, we think the diagnosis of sclerosing thyroiditis NOS would be more appropriate, the histology not being sufficiently characteristic to make a more specific diagnosis.