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A 13‐year‐old Labrador retriever was diagnosed with Cushing's syndrome (CS) caused by primary bilateral nodular adrenocortical hyperplasia with adrenocorticotropic hormone (ACTH) expression. The pituitary origin of CS was ruled out by suppression of plasma ACTH concentration and absence of a proliferative lesion on histological evaluation of the pituitary gland using periodic acid‐Schiff (PAS) staining, reticulin staining, and immunostaining for ACTH. A pheochromocytoma also was found at necropsy examination. On histological evaluation of both adrenal glands, at the junction of the fascicular and glomerular zones, multiple cell clusters distributed in both hyperplastic adrenal cortices expressed ACTH, whereas the pheochromocytoma cells did not. These results indicate that a disease similar to primary bilateral macronodular adrenocortical hyperplasia in humans also occurs in dogs, with intra‐adrenocortical expression of ACTH, glucocorticoids excess, and clinical signs of CS. Therefore, the term ACTH‐independent could be inappropriate in some cases of bilateral adrenocortical hyperplasia and suppressed plasma ACTH concentration in dogs.

Background: Adrenal gland is a lifesaving endocrine gland of the human body. Knowledge of normal microscopic anatomy of the Adrenal gland facilitates Pathologists to correlate and make the differential diagnosis of various adrenal glands associated clinical conditions on histopathological examination. Aims and Objective: To study histological features of human adrenal gland in the post-natal period at different ages. Materials and Methods: Present study is conducted with 98 human adrenal glands from 49 unclaimed dead bodies during an autopsy and 22 human adrenal glands from 11 cadavers during routine dissection in S.V Medical College, Tirupati, which were utilized after obtaining consent from the close kith and kin. During the autopsy/dissection, the samples collected were from 2 Years to 64 years of age individuals of both sex with typical external features and divided into three groups. The first group consisted of less than 25 years of age. The second group consists of ages between 26 years to 50 years. The third group included 51 years and above, and all the specimens are processed for histological staining and observed under the microscope. Results: At 2 years well-developed capsule with large vessels and well-differentiated zones of definitive cortex and medulla were identified. The thick muscular coat of the central vein was identified at 20 years. At 36 years & 45 years, cellular architecture in various zones is very well differentiated. At 65 years, the cortico-medullary demarcation was irregular, and vascularity decreased. Conclusion: Histological features of pre-pubertal, adult, and old age group sections helps in the understanding of post-natal changes in the growth of the Suprarenal gland and its functions.

The reticulin stain is a critical diagnostic aide used to differentiate benign hepatocellular proliferations from well differentiated hepatocellular carcinoma. Rarely, however, hepatocellular carcinomas do not show definitive loss of reticulin in liver biopsy specimens. In order to study this group of tumors, 11 HCC with no reticulin loss in 10 patients were collected and studied. Analysis of demographics showed a typical enrichment for men with a typical age for HCC presentation of 69± 7 years for adults. The background livers showed advanced fibrosis or cirrhosis in 6/6 cases with available information. The tumors were all well differentiated. Cytological atypia was mild and consisted of very mild nuclear atypia (8 cases), mild increase in N:C ratio (3 cases), and pseudorosette formation (4 cases). The cytological/architectural atypia was insufficient in isolation to diagnose HCC. Additional studies, however, showed an increased Ki-67 proliferative rate (N= 10/10 stained cases). The Ki-67 proliferative rate was estimated to be between 5–10% in all tested cases and was clearly increased from adjacent liver at low power. Glypican 3 positivity (4 tumors) and alpha fetoprotein (1/8 stained cases) positivity also helped make the diagnosis of HCC. Morphologically, the HCC had conventional morphology with five showing steatosis / steatohepatitic features and one showing intratumoral fibrosis. A control group of macroregenerative/dysplastic nodules showed no increase in Ki-67 proliferation and no staining for glypican 3. These findings highlight an important diagnostic pitfall: rare HCC show no reticulin loss on biopsy. In these challenging cases, additional findings are useful to make a diagnosis of HCC: increased Ki-67, and positive staining for aberrant expression of proteins such as glypican 3 or alpha fetoprotein (AFP).

Introduction: Non-Hodgkin lymphomas (NHL) comprise a wide variety of neoplasms and are subdivided into two main categories of low grade and high grade lymphomas. The major subtypes among T cell lymphomas are Peripheral T cell lymphomas – Not otherwise specified, Anaplastic Large cell lymphoma, ALK positive, Angioimmunoblastic T-cell lymphoma, T lymphoblastic leukemia/lymphoma and Extranodal NK/T cell lymphoma, nasal type. In this study, the histomorphological diagnostic features and the adjunct immunohistochemical expression of various markers are studied in a tertiary care centre in South India. Materials and Methods: Patients with lymphadenopathy over a period of two years were included in the study. Lymph nodes excised from these patients were routinely processed and examined. After initial examination with H&E stain, appropriate special stains like Reticulin stain, Periodic Acid Schiff stain and Ziehl-Neelsen stains are performed along with the specific Immunohistochemical markers. Results: A total of 30 cases were classified as Non-Hodgkin Lymphoma, high grade, T cell type. Peripheral T cell lymphomas-NOS is found to be the most common tumors accounting for 40% of all high grade T cell NHLs. The next common tumor was Anaplastic Large Cell Lymphoma, ALK positive with 36% of cases. T lymphoblastic leukemia/lymphoma accounted for 10% of cases and the rest of the cases were reported as Angioimmunoblastic T-cell lymphoma (7%) and Extranodal NK/T cell lymphoma, nasal type (7%). Conclusion: Appropriate use of immunohistochemistry aids in the sub-classification of lymphomas according to the recommendations of WHO 2008. But, further molecular studies should be performed for confirmation of the subtyping done by immunohistochemistry. Keywords: High grade lymphoma, Anaplastic large cell lymphoma, Peripheral T cell lymphoma.

Cellular fibromas represent ~10% of ovarian fibromas. Mitotically active cellular fibromas show mild nuclear atypia but ≥4 mitoses/10 high-power fields: the clinical course is usually uneventful but literature review is lacking. A 34-yr-old woman underwent left oophorectomy for a 9-cm ovarian mitotically active cellular fibroma at another hospital. The tumor was cellular (spindle cells in fascicular and storiform patterns) revealing mild atypia and 4 nonatypical mitoses/10 high-power fields without necrotic areas. After 16 yr, the tumor recurred as a 5-cm peritoneal nodule on the anterior sigmoid wall near the sigmoid-rectal junction. Frozen section revealed a spindle cell tumor invading the intestinal tunica muscularis propria: a gastrointestinal stromal tumor was favored as previous history was unavailable at that time. Intestinal resection was performed: no residual tumor was found. The patient was followed-up for 8 yr without further recurrences. The peritoneal nodule showed 2 mitoses/10 high-power fields and pericellular reticulin staining. The tumor was variably positive for vimentin/bcl-2/melan-A/CD56/ER/PR/α-inhibin/CD10/calretinin, focally positive for desmin, negative for pan-cytokeratin/actin/EMA/CD34/HMB45/CD117/CD99/S100/synaptophysin. The Ki67-index was ~9%. To our systematic literature review, 7 additional recurrent cases were reported. We describe a mitotically active cellular fibroma recurring after the longest interval of time. Extensive sampling of difficult cases should exclude malignant areas. Moderate nuclear atypia, tumor rupture, adhesions to pelvic/abdominal organs, infarction with extraovarian involvement, and incomplete excision may lead to relapse but there are conflicting data: prolonged follow-up can be suggested in these cases.

Objectives: To evaluate the role of angiogenesis by the assessment of mean vessel density and to quantify angiogenesis as an important variable in different benign and premalignant endometrial lesions. Materials and Methods: Endometrial biopsies and hysterectomy specimens were examined to evaluate and define any correlation between angiogenesis and different phases and premalignant diseased states of the endometrium. Microvessel counts were performed by examining the microvessels thoroughly in terms of count, morphology and density after staining the tissues by hematoxylin & eosin stain, reticulin stain and immunostain CD 34. Results: A total of 381cases of benign and premalignant endometrial lesions were included in the study. In 135 cases of simple hyperplasias, Microvessel Density (MVD) ranged from 2.4 - 6.7 and Mean MVD was 4.71 on H&E stain and MVD ranged from 2.8 - 8.3 with Mean MVD of 5.39 on reticulin stain. In 105 cases of complex hyperplasias, MVD ranged from 2.3 - 7.0 and Mean MVD was 4.93 on H &E satin and MVD ranged from 3.1-7.7 with Mean MVD of 5.68 on reticulin stain. In 67 cases of atypical hyperplasias, inbudding and outpouching of the glandular epithelium together with multilayering was appreciated with MVD from 4.5 - 8.8 and Mean MVD of 6.31 on H &E stain and MVD of 5.5 - 9.4 with Mean MVD of 7.19 on reticulin stain. A statistically significant difference was noted in all categories except in between simple and complex hyperplasia where the difference was not statistically significant. The role of angiogenesis becomes more significant with increasing severity of lesion, both in terms of hyperplasia and atypia when compared to normal endometrium. Although angiogenesis can be detected on immunostain more easily, it can be illustrated well by H and E or Reticulin stain. Conclusions: Role of angiogenesis becomes more significant with increasing severity of lesion, both in terms of hyperplasia and atypia when compared to normal endometrium. Although an

Introduction: Lymphoma constituting 55.6% of hematological malignancy, its prognosis depends on the correct diagnosis and stage of the disease, which is established after examination of peripheral blood film (PBF), bone marrow aspiration (BMA) and bone marrow biopsy (BMB) along with other parameters. Objective: The objective is to find out the percentage and pattern of bone marrow involvement, along with peripheral blood changes in lymphoma. Material and Methods: PBF, BMA and BMB findings studied in 60 lymphoma patients during a period of 3 years. The PBF and aspiration smears stained with Leishmann’s stain, while the trephine biopsy processed and stained with Haematoxylin and eosin (H & E) stain and Reticulin stain. The results were scrutinized, compared and evaluated. Results: The male to female ratio was 1.4:1, including 53(88.3%) cases of NHL and 7(11.7%) cases of HL. Most common age group involved in NHL was 51-60 years and in HL was 31-40 years. 19/60 (31.7%) cases showed leucocytic lymphocytosis on PBF examination. Percentage lymphocytes in marrow differential count was increased in 16(26.7%) cases and were reported with bone marrow involvement on BMA and BMB and 1 case having borderline percentage lymphocyte count on BMA was reported as bone marrow involved case, only after examining the BMB. The diffuse pattern of involvement was most common in 7(41.2%), followed by paratrabecular pattern in 6(35.3%) cases. Conclusion: Thus to conclude bone marrow examination give valuable information in lymphoma, about disease burden, percentage of involvement, pattern of involvement and baseline involvement prior to therapy. Keywords: Lymphoma, Bone marrow aspiration, Bone marrow biopsy, Bone marrow involvement.

A reticulin staining pattern (RSP) can be used for the differential diagnosis of endocrine gland lesions, as in the adrenal and hypophysis glands. We aimed to use RSP for the differential diagnosis of parathyroid gland lesions. In this study, we evaluated 97 parathyroid lesions in 85 patients, as well as 29 normal parathyroid glands. All sections were stained with a silver impregnation-based kit for the reticulin stain. The RSPs were classified as short thick fiber-, anastomosing- and nodular/alveolar-pattern. The dominant pattern was accepted as being greater than 50% in each section. Short thick fibers and anastomosing and nodular RSPs were seen in adenomas, but there was no alveolar pattern. Although nodular/alveolar patterns were seen in focal areas in hyperplasia, they never became the dominant pattern. Nodular dominant RSPs were seen in adenomas; however, nodular RSPs were not seen in hyperplasia in a dominant pattern (p = 0.049). While short thick fibers were not seen in normal glands, they could be seen in adenomas (p

To study the clinico-haematological and histopathological characteristics of FIP1L1-PDGFRA rearranged hypereosinophilia/hypereosinophilic syndrome (F/P+ve HE/HES), a retrospective analysis of patients with F/P+ve HE diagnosed over a period of 43 months was performed. Peripheral blood smears, bone marrow aspirate (BMA) and biopsies (BMB) were reviewed in each case and; reticulin stain and immunohistochemistry for mast cell tryptase (MCT) and CD117 was performed. F/P+ve HE was diagnosed in a total of ten patients during study period. All patients were males with a median age of 36 years (23–44 years). The median duration of presenting complaints was 7 months (2 months–3 years) which included specific symptoms related to various organs (80% of cases). Anaemia, thrombocytopenia and splenomegaly were seen in 60%, 50% and 90% of the cases respectively. Mastocytosis was not obvious in BMA but identified by MCT on BMB in all cases. Myelofibrosis (grade ≥ 1) was seen in 80% of the cases and includes multifocal paratrabecular fibrosis in 50% of the biopsies. Our study shows that bone marrow mastocytosis and myelofibrosis are very useful morphological indicators to suspect F/P+ve HE and suggests the routine use of reticulin staining and MCT immunohistochemistry in all BMBs performed for the evaluation of HE/HES.

La meningioangiomatosis (MA) es una rara patología hamartomatosa benigna originada de las leptomeninges y corteza cerebral. La asociación con meningiomas es rara. En este caso, presentamos a un hombre de 30 años de edad, sin historia previa de neurofibromatosis tipo 2, quien debutó con cefalea progresiva, disminución de agudeza visual, la cual progresó a amaurosis total del ojo izquierdo. En estudios de imagen revelaron una lesión homogénea localizada en la región frontotemporal izquierda originada de la apófisis clinoides anterior. Fue sometido a cirugía y se encontró un tumor rojizo con apariencia hemorrágica, correspondiente con vasos sanguíneos fibrosados con proliferación de células meningoteliales elongadas que formaban áreas sólidas, resemblantes de un meningioma meningotelial. Resultó ser positivo para EMA, vimentina y el factor VII demostró positividad en células perivasculares y negativo en áreas sólidas. Con la tinción de reticulina se observaron alteraciones en la pared de los vasos sanguíneos. Este caso se discute pues se presenta una masa cerebral formada por vasos sanguíneos anormales, así como con áreas sólidas correspondientes a meningioma.

Sixteen adult granulosa cell tumors which had conspicuous zones of cells with pale cytoplasm imparting a resemblance to thecoma are reported. The neoplasms occurred in patients from 38 to 86 yr of age, the majority being over 55 yr of age. Ten tumors were incidental findings, the remainder being associated with symptoms or signs related to an adnexal mass. All the tumors were unilateral, typically small, usually under 5 cm, with only 3 being larger. With 1 exception they were uniformly solid and were typically entirely or focally yellow on sectioning. Microscopic examination typically showed a nodular pattern of growth constituted by cells with moderate to abundant pale cytoplasm; the cells resembled those seen in most thecomas. The nodules occasionally became confluent and focally a diffuse pattern was seen. Typical foci of adult granulosa cell neoplasia in the form of foci of conspicuous epithelial differentiation were absent or rare in most cases but were seen in subtle form in 6 cases and overtly in 3. A few tumors had other features seen in some thecomas, hyaline plaques, sclerosis, and calcification. Reticulin stains were examined in 13 cases and showed that the thecoma-like foci exhibited a dearth of reticulum indicating that those areas were predominantly of granulosa cell nature. Most adult granulosa cell tumors have cells with scant cytoplasm; occasional tumors have abundant eosinophilic cytoplasm, so-called luteinized adult granulosa cell tumors. That some granulosa cell tumors have the cytoplasmic features described herein has occasionally been noted but the resemblance to thecoma has not been emphasized to the best of our knowledge and in the past such tumors may have been misdiagnosed as thecoma, the referral diagnosis in 6 of our cases. A reticulin stain is of crucial aid in indicating the epithelial nature of the thecoma-like foci in these cases. Given the small size of the majority of the tumors the distinction between a small adult granulosa cell tumor and thecoma does not have significant prognostic or therapeutic implications in most cases but awareness of this feature of a small subset of adult granulosa cell tumors is warranted. Our findings have import to the diagnosis of thecoma which is uncommon if strict criteria, including exclusion of granulosa tumors of the type described, are used.

Sinusoidal obstruction syndrome (SOS) is a unique form of liver injury that occurs after exposure to chemotherapeutic drugs and toxins. The diagnosis of SOS in humans remains a challenge as the clinical criteria have low specificity and there are no reliable noninvasive biomarkers. The mechanism of injury is believed to be damage to liver endothelial cells, primarily sinusoidal endothelial cells (SECs), which leads to sinusoidal dilation, central venous fibrosis, and/or nodular regeneration. Nonclinical data suggest that this uncommon liver toxicity can be recapitulated in cynomolgus monkeys, and it is critical that pathologists are familiar with its characteristic clinicopathologic features. Elevations in liver enzymes, in particular aspartate aminotransferase, associated with isolated thrombocytopenia, should raise the suspicion of SEC injury for specific drug classes. Characterization of liver microscopic findings in monkeys benefits from the use of appropriate stains, such as reticulin stain, and VEGFR2 and CD34 immunohistochemical (IHC) stains. CD41 IHC demonstrates platelet accumulation in injured sinusoids, the likely cause of thrombocytopenia commonly reported in SOS. In conclusion, this report provides a comprehensive characterization of the pathology findings of drug-induced SOS in monkeys with the objectives of ensuring appropriate nonclinical recognition of the liability and informing clinical development strategy and monitoring.

Hepatocellular carcinomas are the most common primary neoplasia of the liver. The global distribution of hepatocellular carcinoma is related to the prevalence of hepatitis C in the population. Other major etiologic factors include alcoholic liver disease and nonalcoholic steatohepatitis. The majority of cases are discovered when screening patients with either chronic hepatitis or cirrhosis, but occasional incidental cases have been reported. Molecular markers and associated gene alterations are a work in progress. Serological markers and radiology are used to detect the disease in high-risk populations, and to monitor response to therapy in the affected patients. Even though radiologic features are specific, tissue diagnosis may be required, particularly for atypical and smaller lesions. Ancillary studies including reticulin stain and immunohistochemistry are important for confirmatory diagnosis. Liver transplantation is curative for hepatocellular carcinoma, but due to limitations in organ availability, palliative care is required, which mostly includes chemoembolization and radio-ablation.

Tacrolimus (TAC) is an immunosuppressive drug, optimally used for liver, kidney, and heart transplant to avoid immune rejection. In retrospect, a multitude of studies have reported effects of TAC, such as nephrotoxicity, diabetes, and other complications. However, limited information is available regarding short-term exposure of TAC on the liver. Therefore, the present study was designed to unravel the effects of short-term exposure of TAC on a rat model. The animal model was established by TAC administration for 6, 12, 24, and 48 h time points. Liver histopathological changes were observed with PAS-D, reticulin stain, and immunostaining of PCNA and CK-7 coupled with glycogen quantification in a liver homogenate. TUNEL assay was performed to evaluate the DNA damage in the liver. Concentration of GSH and activities of SOD and CAT in the serum were measured to assess the antioxidant status, whereas liver tissue MDA level was measured as a biomarker of oxidative stress. Hepatic gene expression analysis of IL-10, IL-13, SOCS-2, and SOCS-3 was performed by RT-PCR. Results revealed marked changes in liver architecture of all TAC-treated groups, as evidenced by sinusoid dilation, hepatocyte derangement, glycogen deposition, and collapsed reticulin fibers. Significant increase in PCNA and CK-7 immunostaining along with the presence of TUNEL-positive cells was revealed in treatment groups as compared to the control group. Serum antioxidant enzyme status was markedly decreased, whereas the liver MDA level was increased in TAC treatment groups indicating oxidative stress induction. The gene expression profile of cytokines was significantly upregulated in treatment groups highlighting an inflammatory response. In conclusion, results of the current study propose that even a short-term TAC exposure can induce change in antioxidant status and lipid peroxidation. Therefore, these factors should be considered to avoid and minimize immunosuppression-related issues in a prolonged course of treatment.

Highlights • A rare case of markedly elevated inhibin B associated with an ovarian thecoma. • Inhibin B lacks specificity as a tumor marker for adult granulosa cell tumor. • A full differential for elevated Inhibin B is important for improved preoperative counseling., Introduction Elevated serum inhibin B is a classic marker of adult granulosa cell tumors. Here we discuss an extremely rare and informative case of elevated inhibin B associated with an ovarian thecoma. Case A 57 year-old postmenopausal female presented with recurrent bleeding and was found to have an adnexal mass with an elevated serum inhibin B level of 1,915 pg/mL (normal range 10–200 pg/mL). With a preoperative diagnosis of adult granulosa cell tumor, she underwent surgical management for what was ultimately a benign ovarian thecoma. The diagnosis of thecoma was confirmed by a pericellular pattern of reticulin staining and the lack of a FOXL2 mutation by molecular testing. Conclusion This case demonstrates that inhibin B lacks specificity as a tumor marker for adult granulosa cell tumor, even at very high levels. Knowledge of benign alternative explanations for this finding can facilitate improved preoperative patient counseling. Pertinent literature is reviewed, with an emphasis on proposed hypotheses for inhibin overproduction.

A 3-month-old male patient arrived at Children’s Hospital ‘Dr. Pedro de Elizalde’ (Buenos Aires, Argentina) with irritability, rejection of food and altered neurobehavioral development. An abnormal mass was found in the right flank on palpation of the abdomen. Laboratory tests showed high concentrations of total serum calcium: 6.24 mmol/L (range of normal values in this age group: 2.20–2.82 mmol/L); low concentrations of parathormone (PTH): 0.175 pmol/L (normal 1.06–7.42 pmol/L) and phosphorus: 0.935 mmol/L (normal: 1.55–2.39 mmoL). Vitamin D measurements of 25(OH) showed normal values (63 nmol/L), considering the age group, where the vitamin D insufficiency is defined in the range of concentrations between 30 nmol/L and 50 nmol/L. Other laboratory test values, including blood cell count, were within normal limits. He was hydrated and initially treated with pamidronate and calcitonin but hypercalcaemia did not revert. ### Imaging-based procedures Abdominal ultrasound and computed axial tomography images (figure 1A) revealed a retroperitoneal heterogeneous complex mass located between the liver and the right kidney, with variable pattern and calcifications, measuring 0.1×0.06×0.06 m. Both kidneys and adrenal glands preserved normal anatomical structure, the spleen was homogeneous. This type of lesion was not observed in other organs or tissues and no free liquid was found. Diagnostic angiography evidenced a highly vascularised tumour, irrigated by the middle colic artery (figure 1B). Figure 1 Clinical procedures for the diagnosis and treatment of the patient (A–C). (A) Computed axial tomography, (B) angiography and (C) tumour mass removed by surgical resection. Analysis of the tumour tissue biopsy (D–I). (D) Typical morphology of neoplastic cells coexisting with peripheral inflammatory infiltrates and (E) intracytoplasmic vacuoles representing small vascular lumina (black arrows) (H&E and PAS, 400×). (F) Reticulin expression (Gordon & Sweets reticulin stain, 400×). Expression of (G) vimentin and (H) CD31 (immunohistochemistry, 400×). (I) Immunostaining for Ki 67 (immunohistochemistry, 400×). Histology revealed spindle to polygonal-shaped neoplastic cells with abundant eosinophilic cytoplasm, arranged in …

Background: Use of the smokeless tobacco is a major public health problem. Oral mucosal hyper keratinization occurs due to smokeless form of tobacco. Objective: To determine the Submandibular Gland injuries induced by smokeless tobacco in Albino Rat. Study Design: Experimental study. Settings: Department of Oral biology, Liaquat University of Medical & Health Sciences, Jamshoro-Pakistan. Duration: From November 1, 2015 to April 30, 2016. Methodology: Aalbano healthy rats were used to observe smokeless tobacco effects on submandibular glands. After initial weight record, rats were placed in three groups (A, B, C); Group-A (control group), group-B and group-C were fed with tobacco; non-smokeless, smokeless 5%, and smokeless 10%, respectively. During experiment, weight gain was recorded weekly and sub-mandibular gland weight was measured at the end of the trial. T-test was applied to analyze the data. H & E stain and reticulin stain were used to observed structural integrity of submandibular gland. All the data was recorded in the self-made proforma. Results: Overall body weight and submandibular weight were decreased in B and C groups as compared to control group. In group A, seromucinous acini was seen in parenchymal tissue, cuboidal epithelium showed duct line and red blood cells distended vessels. Stromal changes, narrow duct lumen and reasonable damage in parenchymal tissue with atrophy were detected in group B. Stromal tissues increased and atrophy of acini were observed in H and E stain during histological study. Further, as compared to control groups, in group B and C under reticulin stain and stromal tissues were enlarged with pragmatic vascular collapse. Conclusion: This study revealed abnormal histological changes in submandibular gland of albino female rats by oral use of smokeless tobacco.

Background: Integrity of ovarian function is a prerequisite for successful implantation of ovum. The subtle changes in ovarian function can be detected by studying endometrial carbohydrates with special stains.Material and methods: 87 infertile and 30 normal endometria were studied with the help of Hematoxylin& Eosin ( H & E) stain and special stains like Best Carmine, Alcian blue PAS (with and without diastase digestion) and reticulin stain.Results: Special stains were useful in emphasizing the cyclical activity of carbohydrates and stroma in normal endometrium. In infertile endometrium, they helped in precise classification and detection of corpus luteal deficiency, at times (8.7% cases) missed on routine H& E stain . Intrinsic abnormalities like polyps and tuberculous granulomas could be detected with ease on reticulin stain. On application of special stains, incidence of corpus luteal deficiency was 27.5%, and that of anovulatory infertility and normal secretory endometrium was 34.5% each. Conclusion: The special stains helped in detecting precise endometrial response and added to the information obtained by routine H&E stain.DOI:10.21276/APALM.1725

Introduction: There are various disorders in formation of blood in body. Bone marrow is one of them which involved variety of hematological and nonhematological disorders. Hematological disorders include myeloproliferative neoplasm (MPN), acute leukemia, hemato-lymphoid neoplasm and nutritional deficiency diseases whereas nonhematological disorders include infectious diseases infiltrating the bone marrow such as parasitic infections, tuberculosis and metastatic deposits. Bone marrows present various diseases with various clinical symptoms with the involvement of blood but peripheral blood picture alone does not reflect the nature of disease process. Depending upon the suspected diagnosis from clinical features and peripheral blood examination, that indication for bone marrow examination can be done. Examination of Bone marrow is useful in the diagnosis of both hematological and non-hematological disorders. The most important techniques used for the diagnosis of hematological disorders are trephine biopsy and bone marrow aspiration. For the interpretation of the disorder of bone marrow history, clinical finding, peripheral blood picture and other laboratory findings are required. Usually Bone marrow aspiration (BMA) alone is sufficient for the diagnosis of nutritional anaemias, most of the acute leukaemias and Immune thrombocytopenias. Diagnosis such as Trephine biopsy provides important diagnostic information myelofibrosis, granulomatous disease and bone marrow infiltration. Bone marrow aspiration is useful in making out better individual cell morphology whereas biopsy is useful in bone marrow architectural pattern and distribution. Bone marrow is nor mocellular or hypercellula resulting from ineffective hematopoiesis, increased peripheral destruction and bone marrow invasion. Therefore, bone marrow examination is extremely helpful to identify the cause of pancytopenia. Aim: The main aim of this study is to evaluate the cytological and histological pattern of various hematological disorders in bone marrow aspiration and trephine biopsy respectively. Material and Methods: During the period of 1 year 100 patient with the cases of haematological disorders were included in this study. Routinely stain like Leishman stain is used for bone marrow aspiration. Haematoxylin and eosin stain is also used for trephine biopsy. For all the cases reticulocyte count, peripheral smears, sickling test and complete hemogram were done. Special stains PAS Stain (Periodic acid schiff) was done for all ALL, AML and gauchers disease. In ALL cases Block positivity is shown. In gauchers disease, a gaucher cell shows wrinkled tissue paper appearance with PAS positivity. Reticulin stain was done in myelofibrosis and metastatic deposits. In myelofibrosis, trephine biopsy shows increase in reticulin network with coarse fibrils. Result: In all the cases bone marrow aspiration was done and among them 40 cases trephine biopsy were done. Out of total patients 57 were male and 43 were female. And the mean age was found as 32.6 years. The findings of the bone marrow were examination. At the time of study period 50% of the study have anemias and they are predominantly megaloblastic followed by aplastic/ hypoplastic anemias. Other three cases include two metastatic deposits and one storage disorder (Gaucher’s Disease). Conclusion: Bone marrow examination is important to diagnosis, prognosis or evaluate therapeutic response for a variety of hematologic and non-hematologic problems. Nowadays, Bone marrow aspiration & bone marrow biopsy are used routinely as diagnostic procedures because it is easier and does not require advance equipments. Therefore both the procedures are complementary to each other which are helpful in further investigation and management. Keywords: Bone marrow aspiration, Trephine biopsy, Pancytopenia, Megaloblastic Anemia

Purpose A case of a small benign storiform fibrous tumor of the conjunctival substantia propria is described to clarify the category of fibrous histiocytoma. In addition, a comparison of the various spindle cell tumors of the conjunctival substantia propria is explored. Methods The patient underwent a complete tumor excision, and the specimen was analyzed by histopathologic and immunohistochemical investigations. Results A cellular mass, composed solely of spindle cells in a storiform pattern without a component of histiocytic cells, was found beneath an undisturbed nonkeratinizing squamous epithelium and was separated from the epithelium by a grenz zone of uninvolved collagen. The lesion was sharply demarcated but not encapsulated. The Masson trichrome stain revealed scant deposition of intercellular collagen. The reticulin stain displayed numerous and delicate wiry fibers between the tumor cells and encircling capillaries. The Alcian blue stain demonstrated faint positivity in the interstitium. Immunohistochemistry revealed positivity for vimentin, factor XIIIa, smooth muscle actin, CD10, and CD45. Negative stains were obtained for CD34, CD56, S100, desmin, and Ki67. Conclusions The broad term of fibrous histiocytoma should be reserved for deep fibroblastic spindle cell tumors (e.g., those of the orbit) that display an aggressive behavior. More benign superficial spindle cell tumors of the dermis are now preferentially characterized as dermatofibromas. It is suggested that equally benign epibulbar tumors should no longer be designated as fibrous histiocytomas but rather as benign storiform fibrous tumors. Tumors completely composed of polygonal histiocytoid (epithelioid) cells that are CD34+ should be excluded from the benign storiform fibrous tumor category. Positive smooth muscle actin and factor XIIIa staining in conjunction with negative staining for CD34 and desmin in the current spindled tumor cells are findings consistent with those of cutaneous dermatofibromas. Both the epibulbar and dermal spindle cell lesions have displayed an indolent and nonaggressive behavior. Microscopically they contain a high proportion of dendrocytic stellate cells that are either factor XIIIa+ or XIIIa-. Given the anatomic differences between the dermis and conjunctiva, the term dermatofibroma is inappropriate for the current tumor; instead the term benign storiform fibrous tumor has been proposed for superficial tumors of the conjunctiva.

Background: Melanotic schwannoma is a rare tumor with indeterminate biologic behavior and varying treatment recommendations. Methods: We report 2 cases of pigmented melanotic schwannoma of the head and neck and perform literature review. The pathologic and immunohistochemical characteristics of melanotic schwannoma are reviewed. Results: Two cases of melanotic schwannoma are presented. Both cases underwent surgical resection with one patient receiving adjuvant radiation therapy. Conclusions: Melanotic schwannoma is a rare nerve sheath tumor that is frequently mistaken for malignant melanoma. We describe 2 cases of pigmented melanotic schwannoma of the head and neck with different presentations and review the histopathological and immunohistochemical features.

Aims: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin–Weiss–Bisceglia (LWB) criteria for oncocytic variant. Materials and Methods: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010–June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records. The functional status of the tumor was noted based on clinical and biochemical evaluation. The location, size, and gross appearance of the tumor were noted. The corresponding hematoxylin and eosin-stained slides were independently assessed by two pathologists applying modified Weiss criteria and LWB criteria for the oncocytic variant as applicable. Reticulin stain was performed on representative sections in all cases. All the tumors were classified according to RA, and the diagnoses made by each system were correlated. Results: There were 15 ACTs in the study period. There were two adenomas including one oncocytoma which showed Weiss score (WS) of 2 and intact reticulin framework. There were 13 adrenal cortical carcinomas including two oncocytic variants with WS ranging from 4 to 7. There was disruption of reticulin and thick, irregular reticulin fibers in all tumors, irrespective of the histology. It correlated with modified Weiss and LWB criteria. Conclusions: The RA was simple, easy to apply, and correlated well with modified Weiss criteria in the diagnosis of ACTs including the oncocytic variant.

Smokeless tobacco is very common personal habit of people living in various areas of Asia which is an alarming sign for the development of different oral diseases in such people. The aim of present study was to investigate effects of smokeless tobacco on parotid glands of the Aalbano rats by using various percentages of the smokeless tobacco. The rats were divided into three different groups, control group (A) no smokeless tobacco, experimental group (B) 5% smokeless tobacco and experimental group (C) 10% of smokeless tobacco with different feeds required according parameters. Weekly weight gain and partid gland were analyzed through student P test and histological structures were recorded through HE stain and Retculin stain. The results showed that as compared to control group body, weight of the rats was decreased in groups B and C having smokeless tobacco percentage in the diet. Weight of parotid gland as compared to control group was decreased in groups B and C with diet of smokeless tobacco. Further, histological observation under HE stain showed that parotid gland of group B showed mild narrowing of ductal lumen, collapse of vessels and stromal was also increased, in group C parenchymal tissues with loss of acini found damaged and glandular dystrop and lymphatic infiltration were determined moderate to severe. Meanwhile, reticulin stain showed that vascular collapses were shown because of increasing in stromal glandular atrophy in group C as compared to control group. In conclusion, this study showed that smokeless tobacco caused serious injuries in the tissue level in parotid gland with high percentage of smokeless tobacco which highlight health hazards on its consumption.

It is still unknown that whether sepsis with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) fit into the conventional diagnostic criteria of sepsis. Our aim was to investigate the potential clinical parameters for the diagnosis of HBV-ACLF with sepsis. A retrospective study was conducted in 43 patients with HBV-ACLF and sepsis who underwent orthotopic liver transplantation. All patients were divided into three groups according to the pathological results and laboratory test results. Immunohistochemistry (IHC) staining, hematoxylin-eosin (HE) staining and Gordon Sweet’s reticulin staining were performed in this study. Alanine aminotransferase (ALT), aspartale aminotransferase (AST), total bilirubin (TBiL), cholinesterase (CHE), albumin (ALB), prothrombin activity (PTA), blood routine examination were detected. The results being chosen at admission and before transplantation were analyzed. TBiL had a significant increase (563.5 ± 191.8 umol/L vs. 383.9 ± 157.6 umol/L, 438.3 ± 154.7 umol/L, P = 0.031) and ALT significantly decreased (81.6 ± 66.4 U/L, 754.5 ± 1084.7 U/L, 120.6 ± 102.5 U/L, P = 0.005) in sepsis group before liver transplantation. When sepsis appeared in patients with HBV-ACLF, the ratio of PLT to WBC count before liver transplantation was much lower than it at admission (4.6 ± 2.0 vs. 16.1 ± 7.2, P = 0.000). In conclusion, the clinical parameters of sepsis in patients with HBV-ACLF should be reset. The ratio of PLT/WBC and (WBCBLT/WBCAA)/ (PLTBLT/PLTAA) could remind us the occurring of sepsis in patients with HBV-ACLF.

Histochemistry has an important, continuing role in the current assessment of hepatic biopsies and resection specimens. The evaluation of connective tissue elements in the liver can be accomplished with such methods as the Masson trichrome, Snook reticulin, Vierhoff van Gieson, orcein, and Victoria blue stains. The results contribute to the diagnosis of acute and chronic hepatitis, submassive necrosis, venous outflow obstruction, steatohepatitis, and cirrhosis. Fat stains done on frozen sections of liver tissue are routinely performed in the evaluation of donor liver allograft biopsies. Iron stains such as Perls' method and the Prussian blue technique contribute to the recognition of hemochromatosis and hemosiderosis. The rhodanine, orcein, and Timm stains for copper are used in the characterization of chronic cholestatic liver disease and Wilson's disease. Labeling of carbohydrate-based moieties in various disorders is accomplished with the digested and undigested periodic acid-Schiff method, and Congo red or crystal violet stains can be employed to detect amyloid deposition. Lastly, evaluations of the thickness of the cell plates and continuity of the reticulin framework, as seen with the Snook reticulin stain, can contribute to the diagnostic separation of benign from malignant hepatocellular neoplasms.

Background: Hepatocellular carcinoma is one of the most common malignancies that account to about half a million deaths yearly and is the third leading cause of death. 80% of these cases are seen in the Asian- Pacific region. Aims of the study were to study the role of immunohistochemistry in differentiating primary from metastatic neoplasms of liver and to evaluate the usefulness of reticulin in differentiating benign from malignant lesions of liver. Methods: 46 cases of hepatic neoplasms reported were taken. Immunohistochemistry was done using the markers Alpha Fetoprotein (AFP), Hep Par 1, Cytokeratin 7 and Cytokeratin 20. Reticulin stain was done in 10 difficult cases to differentiate neoplastic from non-neoplastic lesions of liver. Results: AFP was positive in 18 cases (84%), 20 cases were positive for Hep Par 1 (92%). Among the metastatic neoplasms, the most common expression was cytokeratin 7 positive/ cytokeratin 20 negative expressions which were observed in 54% of cases. Reticulin fibres in the benign processes revealed one-cell thick liver plates, whereas in dysplastic and carcinomatous deposits, they showed thickening of the hepatic cell plates which appeared as two or three cell-cell thick plates. Conclusions: Alpha Fetoprotein and Hep Par 1 are found to be useful in diagnosing hepatocellular carcinomas; and Hep Par 1 is more sensitive than Alpha Fetoprotein. Cytokeratins 7 and 20 were useful in assessing the primary tumour to some extent in case of metastatic carcinomatous deposits of liver. If adequate liver biopsy sample is received, an extended panel of markers can be used to find the site of primary with more accuracy. Reticulin stain can be used in cases where there is difficulty in differentiating neoplastic from non-neoplastic lesions of liver.

Item does not contain fulltext AIMS: Myelofibrosis is the result of aberrant stromal activity which is determined routinely by reticulin staining in bone marrow biopsies. As matrix fibres are the product of activated fibroblasts, we analysed fibre accumulation compared to stromal cell activity during myelofibrosis progression using the fibroblast activation marker platelet-derived growth factor receptor beta (PDGFRbeta) by immunohistochemistry. METHODS AND RESULTS: Initial and follow-up bone marrow biopsies from 84 patients with myeloproliferative neoplasia, including 55 cases with primary myelofibrosis, were evaluated from five haematopathology centres. The stromal mass was measured by conventional reticulin staining [myelofibrosis (MF) grade, 0-3] and PDGFRbeta-positive cells using a novel PDGFRbeta scoring system (0-3). Results were correlated for prediction of progression. The MF grade and the PDGFRbeta score showed excellent correlation (Spearman's r = 0.83, P < 0.0001). Elevated PDGFRbeta scores (higher than MF-grade) predicted myelofibrosis progression in total with 43% sensitivity and 57% specificity, and short-term (within 1 year) progression with 82% sensitivity and 53% specificity. Progression of prefibrotic disease to manifest myelofibrosis could be forecast with 90% sensitivity and 75% specificity. CONCLUSION: PDGFRbeta highlights stromal cell activation in marrow fibrosis, which is closely related to matrix accumulation, indicating a direct clinical impact especially in prefibrotic myeloproliferative disorders.

Approximately 90% of neoplasms found in the sellar region are adenoma of the pituitary gland. The use of frozen sections for the diagnosis of pituitary adenomas has an accuracy of 90% and is useful in evaluating complete tumor removal. However, it is sometimes difficult to diagnose pituitary adenomas using frozen sections because of the small sample size and marked artifact, and the contiguity of the pituitary adenoma with normal pituitary gland tissue. In this study, we evaluated the use of our modified reticulin stain to make correct decision in frozen section with reduced stain time and investigated the objective diagnostic criteria of pituitary adenoma with reticulin stain. We used Gomori's silver impregnation methods to stain reticulin fibers in frozen pituitary gland sections of 36 samples from 24 patients. We modified the conventional staining method by reducing the overall staining time. We diagnosed pituitary lesion according to our interpretation criteria and compared the results to those of the conventional method and findings of hematoxylin and eosin-stained slides. Reticulin fiber staining of normal adenohypophysis outlines the supporting stroma around the blood vessels and shows regular of the gland meshwork interconnecting the capillaries. In contrast, reticulin fiber staining of the adenomatous tissue shows loss of meshwork or frequent fragmentation. Our modified reticulin stain is more rapid than the established method and shows similar levels of accuracy. Independent evaluation by two pathologists showed discrepancies in diagnosis in four out of 36 cases with modified reticulin stain. Our rapid modified reticulin staining method for frozen sections may be useful as a diagnostic tool for pituitary adenomas and can complement routine hematoxylin and eosin staining.

Aims Hepatic angiomyolipoma (AML) often shows epithelioid morphology with inconspicuous fat. Epithelioid component can mimic hepatocellular adenoma (HCA) or carcinoma (HCC). The aims of this study were to examine the expression of commonly used markers for HCA or HCC in hepatic AML and highlight pitfalls in diagnosis. Methods and results Resected hepatic AMLs (n = 16) were reviewed; reticulin stain, immunohistochemistry for glutamine synthetase (GS), β-catenin and liver fatty acid binding protein (LFABP) were performed along with Sanger sequencing of exon 3 of CTNNB1 and next-generation sequencing (NGS). Predominant epithelioid component (≥50%) was seen in 80% of cases. Foamy macrophage was present in 33% of cases. High-risk histological features were often present in tumours with benign outcome: marked atypia (19%), mitoses (20%) and necrosis (33%). GS staining (≥10% of tumour) was seen in epithelioid components in 13 (87%) cases, and was diffuse (>50% of tumour) in six (40%) cases. LFABP staining or nuclear β-catenin staining was not seen in any case. Sanger sequencing and NGS did not reveal CTNNB1 mutation in any tested case. NGS demonstrated TSC2 mutations in all five cases tested. Conclusions The predominance of epithelioid component resembling HCA or HCC is common in hepatic AML. Absence of LFABP and presence of fat can be mistaken for HNF1α-inactivated HCA. Diffuse GS staining can be mistaken for β-catenin-activated HCA or HCC. Diffuse GS expression is not related to CTNNB1 mutation. All tested cases showed TSC2 mutation, supporting this as the driving genetic event for hepatic AML.

Diabetes exhibits increased inflammation, angiogenesis, and apoptosis, three processes attenuated by xanthohumol (XN). Herein, we evaluate the effect of XN-enriched stout beer consumption in hepatic glucolipid metabolism imbalance seen in type 1 diabetes (T1D). Five groups of Wistar rats were established: streptozotocin-induced diabetic rats drinking water, treated with 5% ethanol, stout beer, and stout beer supplemented with 10 mg of XN/L and healthy rats drinking water. Hepatic periodic acid-Schiff, reticulin, sirius red, and oil red O histological staining was performed. Lipogenic enzymes and glucose transporter 2 (GLUT2) expression was evaluated by western blotting. Increased fibrosis in T1D animals was significantly decreased to control levels by XN (3.85 ± 0.38 in T1D-beer versus 1.78 ± 0.27 in controls, p0.05; 2.27 ± 0.69 in T1D-beer + XN versus 1.78 ± 0.27 in controls, p0.05). XN reduced T1D hepatic reticulin staining (9.74 ± 3.78 in T1D-beer, p0.05 versus control) to healthy levels (4.45 ± 1.05 in T1D-beer + XN versus 4.60 ± 0.20 in healthy controls, p0.05). XN consumption interfered with the T1D liver catabolic state, reversing glycogen depletion (22.09 ± 7.70 in T1D-beer + XN versus 4.68 ± 4.84 in T1D-beer, p0.05) and GLUT2 upregulation (1.71 ± 0.46 in T1D-beer + XN versus 2.13 ± 0.34 in T1D-beer, p0.05) and enhancing lipogenesis (1.19 ± 0.11 in T1D-beer + XN versus 1.96 ± 0.36 in T1D, p0.05 for acetyl-CoA carboxylase; 1.10 ± 0.04 in T1D-beer + XN versus 0.44 ± 0.31 in T1D, p0.05 for fatty acid synthase). These findings reveal that XN can be a therapeutic agent against liver metabolic changes in T1D, playing a possible role in the insulin receptor pathways.

This report highlights the utility of the reticulin stain in a completely infarcted chorangioma that facilitated the diagnosis. The patient had normal spontaneous delivery with good neonatal outcome in spite of the large size of the chorangioma and the presence of hydramnios in the antenatal period which may perhaps be due to the complete infarction of the tumor.

Introduction: Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done. Materials and Methods: A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for “melanoma,” “melanocytic nevus,” and “blue nevus”. Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica® 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient. Results: Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern. Conclusion: The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.

Dear Editor, Gaucher disease (GD) is the most common lysosomal storage disease, characterized by glucosylceramide accumulation in macrophages owing to inherited glucocerebrosidase deficiency caused by GBA1 mutation [1]. Clinical manifestations include thrombocytopenia, hepatosplenomegaly, bone pain, osteopenia, dyspnea, and seizure, depending on the organ involved [2]. Among these, neurologic involvement plays a crucial role in the classification of the following three subtypes: GD types 1, 2, and 3, called non-neuronopathic, acute neuronopathic, and chronic neuronopathic types, respectively [1,2]. β-glucocerebrosidase activity in peripheral leukocyte is considered the confirmatory diagnostic indicator of GD [2]. Bone marrow (BM) study to detect Gaucher cells (GCs) with the classical "wrinkled tissue paper" appearance has not been routinely recommended because of procedural risks and false-positive results [3]. We present a patient with recurrent seizures as a sole symptom who was correctly diagnosed as having GD type 3 through a BM study. A 31-yr-old woman with recurrent seizures was referred to our hospital. She experienced the first seizure attack at the age of 23 yr. Despite constant antiepileptic medications at the outpatient clinic, she had drug-resistant myoclonic seizures, intermittently evolving to generalized tonic-clonic seizures, which required 11 hospital admissions during the last three years. The initial complete blood count showed no specific findings other than mild leukopenia, with the following values: hemoglobin, 11.9 g/dL; platelets, 162×109/L; and leukocytes, 3.32×109/L, with normal differential counts (Fig. 1A). Physical examination and abdominal ultrasonography revealed no evidence of splenomegaly or hepatomegaly. Drug-induced leukopenia related with long-term use of antiepileptic medications was initially suspected, but the patient showed mild leukopenia during the recent eight weeks, with leukocyte levels ranging from 3.00×109/L to 3.59×109/L. Accordingly, the attending physician performed a BM study. Fig. 1 Microscopic examination of the patient's (A) peripheral blood (×400, Wright-Giemsa stain) and (B) bone marrow aspiration (×400, Wright-Giemsa stain). (C) Atypical Gaucher cell with vacuolations and typical Gaucher cell with a "wrinkled ... In hypocellular marrow with normal distribution, GCs accounted for 17.5% of all nucleated cells on the aspiration smear (Fig. 1B). Of the GCs, 10.5% showed atypical vacuolations, while the others showed typical fibrillary cytoplasm with an eccentrically placed nucleus (Fig. 1C). Despite the consistent BM biopsy findings of GCs (Fig. 1D), reticulin staining showed no evidence of abnormal reticulin fibrosis (i.e., grade 0). In addition, β-glucocerebrosidase activity test revealed 0.6 nmol/hr/mg protein, which is much lower than the reference limit of 6.0 nmol/hr/mg protein. GBA1 sequencing to confirm the diagnosis revealed two point mutations (i.e., N188S and R257Q), both previously reported as the cause of GD. Under the diagnosis of GD type 3, the patient was given enzyme replacement therapy with imiglucerase (Cerezyme, Genzyme Corporation, Cambridge, MA, USA), and her leukocyte count returned to normal. However, the neurological symptoms did not alleviate, coinciding with the fact that imiglucerase is well known to be unable to penetrate the blood-brain barrier. Owing to the phenotypic variability of GD, which might hinder prompt diagnosis or timely clinical impression, several guidelines for optimal diagnostic algorithm and evaluation steps have been suggested [4,5]. Regardless of GD subtypes, hepatosplenomegaly and thrombocytopenia were considered as the most common clinical features. Therefore, hematologic aspects of GD have been emphasized for the early diagnosis of preventable complications [2,6]. Even though the clinical utility of BM study in GD is controversial, GCs detected in BM have been the most important diagnostic indicator in our patient. The long seizure history was explained on the basis of the BM finding, which suggests the reappraisal of the clinical utility of BM study in GD despite professionally appropriate evaluation. Atypical GCs in BM of type 1 GD were evaluated by using the cytomorphological approach in a recent study, in which seven types, including foamy cytoplasm, multinuclearity, erythrophagocytosis, and cytoplasmic projections, were described [7]. The authors suggested that foamy transformation of GCs might be associated with an abnormal storage pattern triggered by an external factor, possibly seizure attacks in this case. Another recent study focused on the differential clinical utilities of BM biopsy and aspiration to detect the presence of GCs [8]. Although biopsy seemed more sensitive to GCs, our patient showed a comparable percentage of GCs in aspiration and biopsy, which might be related to the absence of abnormal reticulin fibrosis in this case. In conclusion, we report a GD patient with recurrent seizures as the single classical symptom, in whom GC detected in BM indicated the correct diagnosis of GD. Our case might emphasize the clinical utility of BM study for GD, especially in cases of unexplained seizures without prominent hematologic abnormalities. Further studies to investigate the roles of BM study for GD for monitoring enzyme replacement therapy response are expected.