Natural history of primary precursor B lymphoblastic lymphoma of the ovary: report of a rare case.

The involvement of the ovaries in lymphomatous processes is a relatively rare phenomenon. Secondary involvement as a part of systemic disease is common as compared to de novo primary lymphoma. Mostly, primary ovarian lymphomas are diffuse large B cell type, whereas the precursor lymphoblastic lymphomas are extremely rare and only four cases have been reported previously. We herein describe a case of primary precursor B lymphoblastic lymphoma involving both ovaries in a 28-year-old woman which was detected incidentally and spread into the blood after 7 months; consequently she succumbed to the disease.

Cyto-morphological features of extramedullary acute megakaryoblastic leukemia on fine needle aspiration and cerebrospinal fluid cytology: A case report.

Extramedullary deposits may be the presenting feature of acute myeloid leukemia. An early and accurate diagnosis on cytology will aid in correct patient management. This is especially true for patients with acute megakaryoblastic leukemia (AML M7), where bone marrow aspiration may yield only a dry tap. While cytomorphological features of myeloid sarcoma of other types are well recognized due to its rarity, there are only two case reports discussing the morphological details of megakaryoblastic differentiation on aspiration cytology. We present the case of a 25-year-old patient with extramedullary involvement of lymph node and cerebrospinal fluid by AML M7, describing in detail, the morphological features on aspiration as well as exfoliative cytology.

Primary thyroid lymphoma: A series from a tertiary care center in Northern India.

OBJECTIVE: Primary thyroid lymphoma (PTL) is a rare entity, necessitating accurate and early diagnosis, as its management is very different from that of other neoplasms intrinsic to the thyroid. MATERIALS AND METHODS: Cases diagnosed between January 2009 and March 2015 were retrieved, and clinical details were noted. Hematoxylin- and eosin-stained slides were reviewed. Immunohistochemistry (IHC) was performed for immunophenotyping, and cases were classified according to the World Health Organization 2017 classification of hematolymphoid neoplasms. RESULTS: Eleven patients with PTL were identified, with a mean age of 64.6 years (range: 40-76 years), including three males and eight females. Duration of symptoms ranged from 2 to 36 months (mean: 9.3 months). Diffuse large B-cell lymphoma (DLBCL) was most frequent, followed by extranodal marginal zone lymphoma. Most DLBCLs were nongerminal center type. BCL2 was positive in all DLBCLs. Strong p53 immunopositivity was not seen in any of the cases analyzed. CONCLUSION: Histopathological evaluation supplemented by IHC is the gold standard for the diagnosis of PTL. Combined chemoradiotherapy appears to be the best treatment modality, irrespective of histological type. MIB-1 and MUM1 IHC may have a role in identifying DLBCL, particularly in small biopsies. Role of p53 and BCL2 needs further evaluation.

Urorectal septum malformation sequence: a report of seven cases.

Urorectal septum malformation (URSM) sequence is an extremely uncommon anomaly. We report herein seven cases of URSM sequence that were identified after reviewing all autopsies conducted at our hospital over a period of 26 years (1981-2006). The URSM spectrum includes partial and full URSM sequences. Absent perineal and anal openings with ambiguous genitalia are included under 'full URSM sequence', and a single perineal or anal opening draining a common cloaca with an imperforate anus is called 'partial URSM sequence'. Of our seven cases of URSM, three were full URSM sequence and four were partial URSM sequence. Associated renal anomalies were found in all of the cases. Three cases had unilateral renal agenesis and one each had bilateral renal agenesis and bilateral renal dysplasia, respectively. The remaining two cases had unilateral renal agenesis with contralateral kidney showing features of cystic dysplastic kidney and renal hypoplasia, respectively. Congenital anomalies involving other organs were also found in some of the cases. The longest survival period in our series was 10 days, in accordance with the short survival period usually associated with URSM. Five of the patients were females, one was male, and the sex of one neonate could not be ascertained. One of the neonates was from a twin pregnancy; the other twin was normal.

Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease): evidence for a dendritic cell derivation?

Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease is a rare histiocytic disorder of unknown origin. Both dendritic cell and monocyte-macrophage lineage have been considered as the origin of the histiocytes that are classical of the disorder. We analyzed seven cases of Rosai-Dorfman disease to determine the immunophenotypic profile of these cells. Immunohistochemical analysis was undertaken by using: (a) fascin as a novel mature dendritic cell marker; (b) S-100 protein; (c) CD68 (both KP1 and PGM1) as macrophage related markers; (d) CD79a and (e) CD3. The Rosai-Dorfman histiocytes exhibited strong cytoplasmic staining for fascin in all the cases and demonstratedformation of a meshwork of fine dendritic processes emanating from the cell cytoplasm. S-100 protein was uniformly expressed in all the cases. Expression of both KP1 and PGM1 epitopes of CD68 was found to be weak and variable. The phagocytosed lymphocytes were composed of an admixture of both B and T-lymphocytes. The characteristic expression pattern of the histiocytes for fascin along with co-expression of S-100 protein and a consistently weaker and variable expression of macrophage-lineage markers point more towards a dendritic cell ontogeny of these cells. Further, abundant fascin expression and presence of dendritic processes indicate a differentiated or mature dendritic cell phenotype for these cells.

Imaging in intersex disorders.

BACKGROUND: Evaluation of the gonads and internal genital structures is an essential component for evaluation of patients presenting with ambiguous genitalia. Ultrasonography (US) and magnetic resonance imaging (MRI) are the two preferred modalities. OBJECTIVE: To compare US and MRI in patients with intersex for localization of gonads and internal genitalia. PATIENTS AND METHODS: Ten patients with proven intersex disorders were included in the study. Findings from US and MRI were corroborated by those from surgery/laparoscopy. RESULTS: For evaluation of the gonads, MRI was found to be marginally more sensitive than US. For internal genital structures, both modalities were found to be equally sensitive and specific with no false positive results. CONCLUSION: US still remains the modality of choice for screening patients with intersex disorders. MRI is helpful in cases with equivocal US findings.

Comparison of three different staining techniques for intraoperative assessment of nodal metastasis in breast cancer.

Imprint cytology has increasingly been used for intraoperative assessment of nodal status in breast cancer. We carried out this study to compare the efficacy of Jenner Giemsa (JG), hematoxylin-eosin (H&E), and Papanicolaou (Pap) stains for intraoperative lymph node imprint cytology (IIC) in breast cancer. One hundred and seven cases of stage I-III breast cancer were studied. Overall, IIC was accurate in 95.3% cases and had a sensitivity and specificity of 98.5% and 90.0%, respectively. The accuracy of JG (95.3%) was better than that of H&E (90.6%) and Pap (94.0%), although the differences were not statistically significant. Problems encountered included cell loss and drying artifacts with H&E and Pap and the inability to distinguish between tumor cells and histiocytes confidently in tight cellular clusters that were occasionally seen. Opinion was possible in all JG cases, but not in five and four cases by H&E and Pap, respectively. Although the choice of the stain would vary depending on the experience of the pathologist, our work suggests that JG, because of fewer technical problems and superior accuracy, may be preferable over H&E and Pap.

Cytologic characterization of postiodization residual goiter in schoolchildren by fine needle biopsy.

OBJECTIVE: To determine the relevance and utility of fine needle biopsy (FNB) for providing a tissue-level diagnosis during a community-based survey of postiodization residual goiter in schoolchildren in India. STUDY DESIGN: A total of 14,762 schoolchildren (56.0% girls and 44.0% boys), aged 6-18 years, with a countrywide representation, were clinically screened for the presence of goiter. FNB was performed under field conditions by means of a nonaspiration technique from both lobes of goitrous glands. The cytologic diagnosis and findings were correlated with age, sex, goiter grade and biochemical parameters of serum T4, TSH, thyroid microsomal (TMA) and thyroglobulin (TGA) antibodies. RESULTS: The overall prevalence of goiter was 23.0%, with a greater frequency in girls (27.1%) than boys (17.8%). FNB was successful in 75.6% of subjects without any significant complications. The cytologic diagnoses in 1,312 successful cases were colloid goiter (92.8%), Hashimoto's thyroiditis (4.6%), focal lymphocytic thyroiditis (1.7%) and hyperplastic goiter (0.9%). Autoimmune thyroiditis (AIT), which accounted for only 6.3% cases, showed a strikingly different age-specific prevalence between girls and boys. Serologic markers of TMA and TGA at various titers were observed to lack requisite sensitivity and specificity for establishing an accurate diagnosis of AIT. CONCLUSION: The nonaspiration technique of FNB is capable of yielding valuable diagnostic information during an epidemiologic survey of goiter. The technique can be easily performed under field conditions on children without significant complications. FNB is preferable to serologic markers for accurate diagnosis of AIT. A relatively low frequency of AIT, as observed in the present study, raises the possibility of a significant role of environmental goitrogens as the underlying pathogenetic factor in postiodization residual goiter in Indian schoolchildren.

CD68 tumor-associated macrophage marker is not prognostic of clinical outcome in classical Hodgkin lymphoma.

Abstract A novel biomarker, CD68, which marks tumor-associated macrophages (TAMs) in the microenvironment, has recently been reported to affect the prognosis of Hodgkin lymphoma (HL). We aimed to evaluate its role in our patient cohort (n = 100) by utilizing a routine immunohistochemistry method on whole tissue sections and a semiquantitative method for CD68 scoring. Clinical data were taken from medical records. Correlation with baseline characteristics, attainment of complete remission (CR), progression-free survival (PFS) and disease-specific survival (DSS) was done by categorical analysis using different cut-offs of CD68 score and also by taking absolute CD68 score as a continuous variable. There was no significant association between levels of CD68 expression and baseline characteristics or CR after primary therapy. CD68 score (neither categorical nor absolute continuous values) also did not predict for any difference in PFS or DSS. We conclude that CD68 TAM marker does not have prognostic value in HL.

Simultaneous medullary carcinoma, papillary carcinoma and granulomatous inflammation of the thyroid.

Thyroid tumours with both papillary and medullary carcinoma features are rare and represent less than 1% of all thyroid malignancies. These tumours have a different clinical presentation and biological behaviour from tumours that have only papillary or medullary carcinoma features. The phenomenon of mixed thyroid tumours can be observed in two settings--a mixed tumour showing dual differentiation, or a collision tumour. For a precise diagnosis of this rare mixed thyroid carcinoma, fine needle aspiration cytology results should be correlated with serum calcitonin and thyroglobulin levels. The diagnosis should also be confirmed using immunocytochemistry. Surgery is the treatment of choice, and the role of postoperative radioiodine is controversial. We herein report the case of a 35-year-old man with a mixed medullary-papillary carcinoma of the thyroid, which presented with C-cell hyperplasia, granulomatous inflammation and metastasis to the cervical lymph nodes. The patient was treated with total thyroidectomy and nodal clearance. This case highlights the need for awareness of coexistent entities as they warrant separate treatments.

Cushing's disease: results of treatment and factors affecting outcome.

OBJECTIVE: To analyze the therapeutic results of intervention and the factors affecting the outcome of patients with Cushing's disease (CD) cared for at the All Indian Institute of Medical Science (AIIMS), New Delhi. DESIGN: Patients with Cushing's disease treated at a teritiary care centre from January 2000 to December 2009 were prospectively studied. RESULTS: Ninety-seven patients received treatment for CD during this period. Mean duration of follow-up was 3.4 ± 2.2 (mean ± SD) years. Eighty-one patients (83.5%) underwent transsphenoidal surgery (TSS) as the primary treatment modality. Fifty-four patients (66.7%) went into remission after initial TSS; ten (18.5%) of them relapsed after a mean follow-up period of 2.9 ± 2.1 (mean ± SD) years. Histopathologic examination of resected tissue showed corticotroph adenoma in 48 of the 54 (88.9%) who went into remission and 17 of the 27 (63.0%) who did not go into remission after the initial TSS. Sixteen patients with severe hypercortisolism underwent bilateral adrenalectomy (BA) as a life-saving measure which was followed by pituitary surgery 6 to 12 months later. Five patients including one with a large macroadenoma required three or more procedures to achieve eucortisolism. CONCLUSION: Fifty-four out of 81 (66.7%) of our patients with CD had remission following initial TSS, ten of whom relapsed later on. Sixteen patients unerwent BA as a life-saving procedure. Factors affecting outcome were, age, gender, low dose dexamethasone suppression test cortisol value and histologic confirmation of corticotroph adenoma.

Crohn disease in Nepal: true rarity or gross underdiagnosis?

Gross and histopathological examination of a resected segment of ileum in a 72-year-old man with the preoperative diagnosis of small intestinal perforation peritonitis revealed the first-ever diagnosed case of Crohn Disease (CD) at the B P Koirala Institute of Health Sciences, Dharan, Nepal. In view of the recent reports on rising incidence of CD in neighbouring Asian countries, it was decided to perform an exhaustive literature search to find out the documented prevalence of CD in Nepal. It was surprising to find only a single case of CD from Nepal, occurring in the year 1980, to be documented in English literature. Further, the index case of CD presenting with acute abdomen is of interest since only about 100 cases of CD with small intestinal perforation have been so far reported worldwide.

Atypical malignant round cell tumour of the femur.

We report an atypical case of malignant round cell tumour in a 25-year-old man who presented with pain in the left hip of insidious onset and long duration of about 1½ years. Radiologically, the tumour was meta-epiphyseal in location with sparing of the diaphysis and showed a defined, narrow zone of transition. These appearances are contradictory to the well documented classical features of malignant round cell tumours, which usually present with a short history, are meta-diaphyseal in location, and appear ill-defined with a wide zone of transition due to infiltration of the adjacent bone.

Myelolipomatous change in an interhemispheric lipoma associated with corpus callosum agenesis: case report.

OBJECTIVE: Interhemisperic lipomas are almost always associated with hypogenesis or agenesis of the corpus callosum. These lesions are stable. CLINICAL PRESENTATION: We report a case of an interhemispheric lipoma in a 72-year-old man who had undergone myelolipomatous differentiation. INTERVENTION: Gross total excision of the lesion was performed. CONCLUSION: Although extremely uncommon, the possibility of myelomatous change should be considered in the differential diagnosis of an intracranial lipoma if it shows some areas of mixed density.

Management challenges in a child with hyperinsulinemic hypoglycemia.

Malignant insulinoma is very rare in children. Herein, we present a case of a child with malignant insulinoma along with islet cell hyperplasia. She initially presented with features of hyperinsulinemic hypoglycemia at 18 mo of age. Magnetic resonance imaging (MRI) of the abdomen showed a mass at the junction of the head and body of the pancreas. The tumor was enucleated. Five months later symptoms of hypoglycemia recurred. A subtotal pancreatectomy was performed. She continued to have hypoglycemia, although less frequently. She was put on increasing doses of diazoxide. Seven months later, MRI of the abdomen and a PET scan revealed metastatic deposits in the liver, which were confirmed by histopathology and immunostaining. To the best of our knowledge, this is the youngest child with metastatic insulinoma reported so far.

Apoptosis and proliferation: correlation with p53 in astrocytic tumours.

Apoptosis and cell proliferation occur simultaneously in tumour tissue with tumour suppressor gene, p53 being one of the key players in the complex relationship between these two key phenomena. We, as well as several other groups, have earlier demonstrated the association of p53 immunopositivity with increased degree of cell proliferation in astrocytic tumours. Here we have studied the extent of apoptosis in 62 primary human astrocytic tumours [25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative status and p53 protein expression. Apoptosis was measured by the TUNEL assay while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and more in tumours with p53 immunopositivity than in those without. The most striking observation was the strong correlation between Apoptotic index (AI) and proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or in low grade DA either p53 positive or negative. Taking p53 negativity in IHC as evidence of a functional gene/protein, this extends the link between proliferation and apoptosis, hitherto observed only in cultured cells with functional p53, to a subset of solid tumours.

Are childhood and adult medulloblastomas different? A comparative study of clinicopathological features, proliferation index and apoptotic index.

Childhood medulloblastomas have been suspected to be biologically different from adult tumors, though comparative studies are sparse in the literature. The present study aims to establish any differences or nexus in the biological characteristics between childhood and adult medulloblastomas. A total of 181 medulloblastomas were studied with respect to clinical and histological characteristics, MIB-1 labeling index (MIB-1 LI), apoptotic index (AI), ratio of apoptotic to LI, p53 and Bcl-2 protein expressions. Two-thirds (112) of the 181 medulloblastomas occurred in children (< or = 15 years) and 69 in adults (> 15 years). Childhood tumors were more commonly of classical histology and midline location while the desmoplastic variant and lateral location occurred more frequently in adults. Adult medulloblastomas were biologically less aggressive, having lower growth rate parameters (mean MIB-1 LI 19.1 +/- 15.7; AI 3.73 +/- 2.71 and AI:LI 0.207 +/- 0.162) as compared to childhood tumors (mean MIB-1 LI 28.3 +/- 20.4; AI 2.86 +/- 2.14 and AI:LI 0.108 +/- 0.111). p53 and Bcl-2 protein expressions were infrequent in all groups of tumors. No difference was noted in any of the parameters when classical and desmoplastic medulloblastomas were compared as a whole. But when compared between the age groups, an interesting observation (hitherto unreported in English literature) was that both classical and desmoplastic variants of childhood medulloblastomas had higher LI, lower AI and lower AI:LI ratio than their counterparts in adults, indicating that differences in growth rates cannot be attributed to differences in the frequency of occurrence of the histological variants in the two age groups. Thus, this study conclusively shows that there is a biological difference between childhood and adult medulloblastomas which is independent of standard histology and appeared to be associated more with age-related factors. This also warrants less-aggressive therapy for adult medulloblastoma.

Touch imprint cytology of axillary lymph nodes after neoadjuvant chemotherapy in patients with breast carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NC) reportedly downstages axilla in approximately one-third of patients with locally advanced breast carcinoma (LABC). Postchemotherapy axillary lymph node status is an important prognostic factor. In the current study, the authors evaluated the reliability of touch imprint cytology (TIC) in detecting axillary lymph node metastasis after NC and identified chemotherapy-induced changes that may influence this assessment. METHODS: Thirty-three patients with LABC were studied. Seventeen patients had received chemotherapy before surgery (NC group) and 16 patients had not (non-NC group). Touch imprints were made from either the largest axillary lymph node (in 13 patients from the NC group and 16 patients from the non-NC) or the sentinel lymph node (in 4 patients from the NC group). Imprints from the NC group were evaluated for metastasis and were correlated with histopathology. Touch imprints from both groups were compared for cellularity, tumor load, necrosis/degeneration, and histiocytes. RESULTS: Cytologic evaluation for metastasis was 100% concordant with histopathology in all 17 patients from the NC group (9 positive results [53%] and 8 negative results [47%]). The presence of few tumor cells in sparsely cellular imprints that exhibited necrosis (two patients) and the presence of only degenerating/necrotic tumor cells (two patients) were two cytologic patterns unique to post-NC imprints that may have influenced their accurate assessment. CONCLUSIONS: TIC was found to be reliable for the intraoperative evaluation of axillary lymph node metastasis after NC. However, a careful examination is warranted in sparsely cellular imprints, because there is the possibility of overlooking a small group of tumor cells. To the authors' knowledge, the significance of finding extensive necrosis in axillary lymph nodes after NC is not known and may be investigated.