Dyskinesia in a child: a concern for a rare neuro-metabolic disorder

A 3-year child is discussed who presented with dyskinesia, large head size, developmental delay, and recurrent infections necessitating multiple hospital admissions. The diagnosis was not made at initial presentation or even after multiple hospital admissions. An organic acidemia was suspected, based on raised ammonia and lactate levels and metabolic acidosis and the diagnosis of glutaric aciduria Type 1 was established by finding markedly elevated levels of glutaric acid and its specific metabolites on urine organic acids analysis by gas chromatography-mass spectrometry, in the setting of specific clinical features. Further supporting evidence was provided by CT scan brain showing subdural hygroma along left cerebral hemisphere causing gyral flattening and widening of sylvian fissure

Direct susceptibility testing on MGIT 960 TB system: a rapid method for detection of drug resistant tuberculosis

Objective: To evaluate direct drug susceptibility testing on MGIT 960 system for detection of multidrug resistant tuberculosis from smear positive pulmonary specimens

Study Design: Cross-sectional analytical study

Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi, from July 2016 to September 2017

Methodology: Smear positive specimens were pretreated according to guidelines and then tested on MGIT 960 TB system for direct drug susceptibility testing [DST] of isoniazid and rifampin. Samples were also processed by gold standard indirect method, which comprises culture and then DST from positive growth by MGIT 960 TB system

Results: Out of 108 specimens, 95 [88%] DST results were reportable. Out of 95 reportable specimens, 17 isolates were resistant to both isoniazid [INH] and rifampin [RIF] by direct DST. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for INH were 92%, 93%, 82%, 97% and 92.6%, respectively; and 95%, 96%, 86.3%, 98.6% and 95.7%, respectively for RIF. Average time to report DST by indirect method was 23.6 +/-3.9 days, while it was 11.4 +/- 2.7 days for the direct method

Conclusion: Direct susceptibility testing on MGIT 960 system showed very good agreement when compared with indirect method. Time saving is crucial factor in initiation of early effective therapy, especially in drug resistant cases. Further studies on large scale are required for more accurate evaluation of this method

Analysis of Estrogen receptor [ER] and Progestrone receptor [PR] expression in surface Epithelial Tumors of Ovary and its correlation with their clinical stage

Objective: To evaluate ER and PR expression in epithelial ovarian cancers [EOC] and to determine its association with clinical stage

Study Design: Cross sectional study

Place and Duration of Study: Histopathology department, Armed Forces Institute of Pathology [AFIP] Rawalpindi, from Mar to Oct 2017

Material and Methods: A total of thirty three [n=33] histologically confirmed EOCs were analyzed. ER and PR expression status was assessed by immunohistochemistry using Allred scoring system and was compared with the clinical stage defined by The International Federation of Gynecology and Obstetrics [FIGO] staging system

Results: A total of thirty three [n=33] females were enrolled. Mean age of the study females was 50.8 +/- 12.9 years. Most frequent histologic type was serous carcinoma [SC] 60.6 percent [n=20] followed by mucinous carcinoma [MC] 15.2 percent [n=5], endometrioid carcinoma [EC] 9.1 percent [n=3], clear cell carcinoma [CC] 9.1 percent [n=3], Brenner tumor [MBT] 3 percent [n=1] and seromucinous carcinoma [SMC] 3 percent [n=1]. Most patients were in clinical stage I 61 percent [n=20] followed by stage II 24 percent, [n=8] and stage III 15 percent [n=5]. Among SC, 90.0 percent [n=18/20] were ER and 65 percent [n=13/20] were PR-positive. All MC and CC were ER/PR negative. Two of the three ECs were ER and one was PR-positive. Higher percentage of stage I tumors exhibited ER 65 percent [n=13/20] and PR 45 percent [n=9/20] positive status [p>0.5]. The correlation was very weak positive between clinical stages and both ER and PR scores [Allred] r=0.11 and 0.15 respectively p>0.05

Conclusion: Higher percentages of stage I tumors exhibited ER and PR positive status yet not statistically significant from stage II/III. Estimation of ER and PR receptor status may help to select the women with ovarian malignancy for hormonal therapy, which is more likely to improve the response rate

Two years experience of analytical and diagnostic challenges in urine organic acid analysis on gas chromatography-mass spectrometry

Objective: To evaluate the analytical and diagnostic challenges in interpreting the various organic acid results by gas-chromatography-mass spectrometry and to devise a protocol for analysis that is beneficial for prompt interpretation and diagnosis

Study Design: Retrospective study

Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from Apr 2015 to May 2017

Material and Methods: We reviewed clinical data, biochemical investigations and urine organic acid profiles of 110 patients received for evaluation of a suspected organic acid disorder. Urine organic acid analysis was carried out by gas chromatography - mass spectrometry using Mass Hunter software

Results: A total of 104 [99 percent] cases received were from the pediatric patients and 7 [6.3 percent] from adult patients. A total of 11 different organic acidurias were diagnosed. Other diseases [n=10] were also detected on the basis of their pathognomics metabolites and included tyrosinemia type 1 [n=4], alkaptonuria [n=5] and ornithine transcarbamoylase deficiency [n=1]. Twenty eight [25 percent] urine samples were either recalled or repeated for reasons like random urine sample yielding negative profiles in setting of a strong suspicion for organic aciduria [n=6], non-availability of clinical data [n=12] or delay in transportation >8 hours [n=10]. Raised non-specific organic acid metabolites were seen in 23 [21 percent] cases. Lactic acid and ketones were detectable in 12 [11 percent] samples in the absence of raised plasma levels

Conclusion: Urine OA profiles must be interpreted in context of complete clinical, nutritional and biochemical findings. Each laboratory equipped with this facility should devise their analytical protocols for meaningful interpretation of results

Immunohistochemical expression of CD10, BCL6 and MUM1 in differentiating diffuse large B cell lymphoma subtypes

Objective: to determine the immunohistochemical expression of CD10, BCL6 and MUM1 in differentiating diffuse large B cell lymphoma subtypes. Study Design: Descriptive, cross-sectional study

Place and Duration of Study: department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from November 2014 to May 2015

Methodology: newly diagnosed cases of DLBCL on HandE stain as well as IHC markers, according to WHO blue book 2008, were included in the study. Patients' gender, age and site of lymphoma were noted. DLBCL subtypes [GCB and activated type or non-GCB] were assessed based on IHC expression of CD10, BCL6 and MUM1 and the results were recorded. The data were analyzed by using computer software program SPSS version 20. Descriptive statistics, frequencies and percentages were calculated

Results: out of 96 patients, 79 [82%] were male and 17 [18%] were female. Mean age was 54.66 +/-16.73 years. Thirty-six [37.5%] cases showed positivity for CD10 and BCL6 both [GCB type], whereas MUM1 was positive in 60 [62.5%] cases [non-GCB type or activated type]. A significant statistical association was seen between expression of IHC markers [CD10, BCL6 and MUM1] and DLBCL subtypes [GCB and non-GCB type, p<0.001]

Conclusion: in Pakistani population, the frequency of non-GCB type expressing MUM1 is 62.5%, which is quite high as compared to western countries. It needs to be further explored, because it represents high-risk subsets in which alternative strategies for diagnosis and management should be planned

Cytomorphological spectrum of testicular fine needle aspiration cytology in cases of azoospermia

Objective: To determine the frequency of morphological spectrum of FNAC in cases of azoospermia

Study Design: Descriptive, cross sectional study

Setting: Department of Pathology, Combined Military Hospital, Multan, from 15th December 2016 to 15th June 2017

Materials and Methods: A total of 112 patients were selected according to inclusion and exclusion criteria, that is age range between 20-50 years with history of azoospermia for at least 1 month on the basis of semen analysis. Patients with already known diagnosis, patients with history of orchiectomy or patients with history of radiotherapy and chemotherapy were excluded. Patients were informed about the procedure, their consent for the procedure and for participating in our study were taken. Procedure was performed under spermatic cord block, slides were prepared and reported by consultant histopathologist

Results: Mean age was 31.6 years with standard deviation of +/- 5.91. All of the patients were married. Only 10 out of 112 patients had history of diabetes mellitus and only 5 out of 112 patients had family history of azoospermia. Mean BMI was 22.74 with standard deviation of +/- 2.95. The mean duration of marriage was 4.62 years with standard deviation of +/- 3.09 and mean duration of azoospermia was 2.69 years with standard deviation of +/- 2.23.Among the patients, 109 out of 112 patients had diagnostic FNAC finding while 3 out of 109 patients yielded unsatis factory results. Among the cytomorphological patterns, hypospermatogenesis was the most common pattern which was observed in 32.1% of the patients. Normal spermatogenesis was seen in 18.8 percent of patients, maturation arrest was seen in 19.6% patients, sertoli cells only was seen in 26.8% patients. 2.7% patients had unsatisfactory sample. A non-significant statistical association was seen among age, disease duration, diabetes and family history with p value > 0.05

Conclusion: This study was conducted to ascertain cytomorphological patterns of testicular tissue among targeted population and to determine the frequencies of these patterns in our population. This study concluded that FNAC testis is a satisfactory procedure for evaluating the cause of azoospermia and FNAC sample in 97.3% of the patient's was satisfactory for evaluation. Hypospermatogenesis was the most common cytomorphological pattern seen in 32.1% of the patients which was followed by sertoli cells examine only which was seen in 26.8% of the patients. Non significant association was found between patient's age, duration of disease, family history or diabetes mellitus with any of the cytomorphological pattern

Clinicopathological characteristics of nasal polyps with chronic sinusitis

Objective: To evaluate the clinicopathological characteristics of nasal polyps associated with chronic sinusitis in polypectomy specimens

Materials and Methods: A total of 78 cases clinically presenting with signs and symptoms of chronic sinusitis with nasal polyps were studied over a period of 2 years

Results: Out of 78 cases 57 were non-neoplastic and 21 were neoplastic polyps, out of these only two cases were malignant. Non neoplastic polyps were bilateral in 37 cases and unilateral in 30. Majority among non neoplastic category were of inflammatory polyps [53.73%]. Other types included allergic 26.86%, fungal infection with polyp 14.92% and lymphocytic category 4.47%. Majority of the cases that is 93.58%, including all types of polyps presented with nasal obstruction and signs and symptoms of chronic sinusitis

Conclusion: Nasal polyps with chronic sinusitis diagnosed clinically are not always non-neoplastic in nature. Hence, histopathological evaluation in all such cases is essential to diagnose both benign and malignant masses

Pattern of malignant renal tumours using 2004 who classification of renal tumours on radical nephrectomy

Objective: To determine the type of malignant renal tumours subjected to radical nephrectomy at a tertiary care urology unit using the 2004 WHO classification for renal tumours. Methods: It was an observational study conducted at Department of Urology, AFIU Rawalpindi, from October 2008 to September 2010. The study included 92 patients with malignant renal tumours of both genders aged above 15 years. The histopathological types and grades were recorded along with the gross tumour presentation. The data was entered in structured proforma and analysed for descriptive statistics using SPSS-14. Results: Over the span of 24 months study, 92 cases of malignant renal tumours were subjected to radical nephrectomy. The age was 16–82 [57.23 +/- 14.61] Years and male to female ratio was 2.1:1. The lesions were mostly unifocal [96.7%] and 58.6% affecting the right side. The commonest malignant renal tumour encountered was the conventional clear cell renal carcinoma [78.2%]. The other tumours in descending order were the transitional cell carcinoma [7.6%], papillary [chromphilic] renal cell carcinoma [6.5%], renal cell carcinoma unclassified [3.2%], chromophobe renal cell carcinoma [2.1%], Wilm's tumour and oncocytoma [1.7%]. T1 lesions were found in 42 cases [45.6%], T2 lesions in 25 cases [27.1%], T3a lesions in 17 cases [18.4%] each, while 8 cases [8.6%] had T3b lesions. Four cases had high and 3 had low grade lesions in transitional cell carcinoma. Wilm's tumour had favourable prognosis, 1 case had oncocytoma limited to kidney. Among the rest, 26 [28.2%] were G1, 35 [38%] were G2, 16 [17.3%] were G3, and 6 [6.5] were G4. Conclusion: The commonest type of the malignant renal neoplasm remains the clear cell [conventional] renal cell carcinoma. The lesions from T1 to T3 are amenable to radical nephrectomy and may not include the ipsilateral adrenalectomy as well. The grade may range from G1 to G4

Sclerosing lipogranuloma of the inguinoscrotal region

Sclerosing lipogranuloma [SLG] is a rare disorder which involves subcutaneous fat and is characterized by granulomatous inflammation. We report a case of 45 years old male who presented with one month history of swelling in the inguinoscrotal region

Oral focus of infection: correlation with intestinal disorder [report of two cases]

The present study describes the findings of complete recovery of intestinal disorder [Chronic dysentery] after extraction of impacted molar teeth in two patients, complaining of facial pain and swelling. These observations, therefore, necessitate the intra-oral checkup for any focus of infection in the mouth that may implicate systemic disturbances