Incorporation of the Milan system in reporting salivary gland fine needle aspiration cytology-An insight into its value addition to the conventional system.

BACKGROUND: Milan System for Reporting Salivary Gland Cytology (MSRSGC) was introduced to standardise the terminology and reporting of salivary gland cytology. The purpose of our study was to compare the conventional system and the proposed Milan System to look for concordance rates in cytohistopathologic correlation and any value addition to the conventional system. METHODS: This was a retrospective cross sectional observational study. The fine needle aspiration cytology (FNAC) were reported in the conventional manner and were correlated with the surgical specimen. The cyto-histopathological correlation was studied to look for concordance rates. FNAC were retrospectively reviewed and were categorised according to the Milan system. These reports were correlated with surgical specimen category wise and concordance rates, risk of neoplasm (RON), risk of malignancy (ROM) were calculated. RESULTS: Salivary gland FNAC done during the study period was 323 in number and histopathological correlation was available for 153 cases. The concordance rate of type specific diagnosis was 80.3% as per conventional system. With the application of Milan system, the concordance rates rose to 88.07% with an improvement of 6.67%(excluding non-diagnostic). RON and ROM for non-diagnostic (I)-50%, 50%; non-neoplastic (II)-22%,0%; atypia of unknown significance (III)-66%, 11%; benign neoplasm (IVA)-98%, 3%; salivary gland neoplasm of uncertain malignant potential (IVB)-93%,14%; suspicious for malignancy (V)-100%, 60% and malignant (VI) was 100%, 94%. CONCLUSION: The broad categorisation provided by the Milan system represents the gross rate of malignancy and helps in deciding the management plan and eventual surgical plan. Thus, it adds value to conventional reporting of salivary gland cytology.

Cabergoline-associated erythema nodosum.

OBJECTIVE: To report a case of erythema nodosum (EN) and related inflammatory arthropathy in a patient on cabergoline therapy for a microprolactinoma. CASE SUMMARY: A 25-year-old white female, who had been receiving cabergoline 0.5 mg orally once per week for the preceding 2 months for a microprolactinoma, developed classic skin lesions of EN (proved by histology) and an associated acute inflammatory arthropathy of her left ankle joint in the absence of any other identifiable causes of EN. She improved substantially (skin lesions of EN and inflammatory arthropathy disappeared) after cessation of cabergoline therapy. Rechallenge with cabergoline in a lower dose of 0.25 mg orally once per week led to a milder recurrence of EN lesions that once again disappeared after withdrawal of the drug. She had not had a recurrence at a 3 month follow-up visit. DISCUSSION: Although possible autoimmune adverse effects (pleuropulmonary and cardiac) have been reported with the use of cabergoline, to the best of our knowledge, this is the first case report of EN (panniculitis) associated with cabergoline therapy. Causality assessment using the Naranjo probability scale revealed that the adverse drug event was probable. CONCLUSIONS: Cabergoline was probably associated with EN (panniculitis) and the related arthritis in a patient being treated for a microprolactinoma. Panniculitis, like EN, needs to be considered a possible but reversible adverse effect of cabergoline therapy for microprolactinoma of the pituitary gland.

Miller fisher variant of guillain-barre syndrome requiring a cardiac pacemaker in a patient on tacrolimus after liver transplantation.

OBJECTIVE: To report a case of Miller Fisher syndrome (MFS), a variant of Guillain-Barre syndrome (GBS) necessitating the placement of a permanent cardiac pacemaker in a patient on tacrolimus after a cadaveric orthotopic liver transplantation. CASE SUMMARY: A 46-year-old African American male, who had been receiving tacrolimus 4 mg/day orally for the preceding 6 months, developed a Miller Fisher variant of GBS (severe ataxia, ophthalmoplegia, areflexia). He developed symptomatic sinus pauses requiring a cardiac pacemaker. He improved substantially after cessation of tacrolimus and initiation of intravenous immunoglobulin therapy. The patient was not rechallenged with tacrolimus due to the clinical/ethical gravity of this probable adverse effect. DISCUSSION: Although different types of neuropathies have been reported with the use of tacrolimus, to the best of our knowledge, this is the first case report of a Miller Fisher variant of GBS severe enough to cause dysautonomia requiring a cardiac pacemaker associated with the use of this drug. Causality assessment using the Naranjo probability scale revealed the adverse drug event was probable. CONCLUSIONS: Tacrolimus was probably associated with a Miller Fisher variant of GBS necessitating the placement of a permanent cardiac pacemaker in this patient. MFS needs to be considered a potentially life-threatening adverse effect of tacrolimus therapy.

Bronchiolitis obliterans with organizing pneumonia in rheumatoid arthritis--a fatal case and short review of literature.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is characterized by excessive proliferation of granulation tissue within small airways (proliferative bronchiolitis) and alveolar ducts associated with chronic inflammation in the surrounding alveoli. It is generally idiopathic but may occur during the resolution of viral or mycoplasmic pneumonia. It is also associated with a variety of systemic illnesses and clinical settings. Complete resolution occurs in 65-85% of patients treated with corticosteroid therapy, and recurrence is not uncommon. Although rapidly fatal BOOP is rare, respiratory failure leading to death may occur in up to 5% of patients. We describe a fatal case of BOOP suspicious for pneumonia in a patient with rheumatoid arthritis.

Celecoxib-induced methemoglobinemia.

OBJECTIVE: To report a case of acute methemoglobinemia in a patient treated with celecoxib for osteoarthritis. CASE SUMMARY: A 72-year-old African American man developed an acute confusional state (ACS) one month after receiving celecoxib for osteoarthritis of his knee joints. There was no other identifiable cause of ACS such as any recognized cause of metabolic encephalopathy, meningoencephalitis, cerebrovascular accident, or drug intoxication. He was found to have severe methemoglobinemia (serum methemoglobin fraction 9%; reference range 0-0.2). His symptoms improved substantially, and serum methemoglobin levels decreased to 0.7% after the initiation of methylene blue therapy. He was discharged on oral riboflavin and ascorbic acid and was advised not to restart celecoxib therapy. He had not shown any recurrence of the symptoms at a follow-up visit 2 months after the withdrawal of celecoxib. DISCUSSION: Celecoxib is a nonsteroidal antiinflammatory drug that selectively inhibits cyclooxygenase-2. Acute methemoglobinemia can present as a syndrome of nonspecific symptoms such as headache, nausea, fatigue, dyspnea, and lethargy; these may progress to respiratory depression, coma, shock, seizures, and death. Although acute methemoglobinemia has been reported with the use of several drugs, including sulfonamides, as of August 13, 2004, this is the first case report of severe methemoglobinemia manifesting as ACS with celecoxib therapy. Use of the Naranjo probability scale indicated a probable relationship between the clinical manifestations of methemoglobinemia and celecoxib therapy in this patient. CONCLUSIONS: Celecoxib can be associated with acute methemoglobinemia. Prompt diagnosis of this condition, withdrawal of celecoxib, and treatment with the antagonists (methylene blue, ascorbic acid, riboflavin) can reverse this potentially serious condition.

Acute onset of severe dilated cardiomyopathy during bromocriptine therapy.

OBJECTIVE: To report a case of severe dilated cardiomyopathy (DCMP) in a patient on bromocriptine therapy for a microprolactinoma. CASE SUMMARY: A 31-year-old African American female, who had been receiving bromocriptine 5 mg orally daily for a microprolactinoma during the preceding month, developed severe DCMP. An echocardiogram showed a markedly dilated left ventricle with severe reduction in the left-ventricular ejection fraction in the absence of any other identifiable causes of DCMP such as a peripartum state, ethanol use, preceding systemic viral illness, chronic hypocalcemia, chronic hypophosphatemia, or chronic uncontrolled tachycardia. She improved substantially (both symptomatically and echocardiographically) after cessation of bromocriptine therapy and initiation of supportive treatment of congestive heart failure (CHF). She showed no recurrence of CHF at a follow-up visit 2 months after withdrawal of the supportive care. The patient was not rechallenged with bromocriptine due to the clinical/ethical gravity of this probable adverse effect. DISCUSSION: Although cardiopulmonary adverse effects have been reported with the use of cabergoline (another dopamine agonist), to the best of our knowledge, this is the first case report of severe life-threatening DCMP associated with bromocriptine therapy. Causality assessment using the Naranjo probability scale revealed that the adverse drug event was probable. CONCLUSIONS: Bromocriptine was probably associated with DCMP in a patient being treated for a microprolactinoma. Severe DCMP needs to be considered a potentially life-threatening but reversible adverse effect of bromocriptine therapy for microprolactinoma of the pituitary gland.

Efficacy of reconstituted and stored botulinum toxin type A: an electrophysiologic and visual study in the auricular muscle of the rabbit.

Once botulinum toxin type A is reconstituted, the manufacturer recommends that it be used in approximately 4 hours. As a result, a significant amount of this costly drug is often discarded because it is not completely used in the recommended period. The purpose of the present study was to compare fresh versus stored reconstituted botulinum toxin type A for (1) initial potency, (2) duration of action, and (3) bacterial colonization. Using a rabbit model, 20 New Zealand White rabbits were divided into four groups (I to IV). All rabbits had an injection of 2.5 U of reconstituted botulinum toxin into the right anterior auricular muscle. The first group was injected with botulinum toxin type A that was freshly reconstituted and served as the control. The second, third, and fourth groups were injected with botulinum toxin type A that had been reconstituted and stored for 2, 6, and 12 weeks, respectively, in a conventional freezer. Each rabbit had daily visual evaluation of the ear, with the position of auricle being graded from I to III. In addition, each rabbit had a nerve conduction study performed on the right anterior auricular muscle before injection and every 2 weeks after injection. Amplitude was chosen as the principal variable in the data analysis because it is the best predictor of physiologic changes at the muscle motor unit level. The endpoint of the study was defined as the time at which the nerve conduction studies and the visual inspections returned to baseline, preinjection levels. Botulinum toxin type A was also cultured before injection into each group.Overall, the nerve conduction data revealed a trend with a faster recovery (return to baseline) with the stored botulinum toxin. Groups IV and III returned to baseline first, followed by groups II and I. However, there was no significant difference among the groups at 2 and 4 weeks after injection, indicating that initial potency was unchanged. The differences between the groups became significant (p < 0.05) at 6 weeks and onward, suggesting that the duration was affected. Group I (fresh botulinum toxin) and group II (toxin stored for 2 weeks) had comparable outcomes and were not significantly different at any time period. Under visual inspection, the mean recovery time for each group was as follows: group IV, 5.4 weeks; group III, 7.0 weeks; group II, 6.75 weeks; and group I, 7.80 weeks. The results showed significance (p < 0.05) beginning after 3 weeks among some groups. Again, there was an overall quicker trend to return to baseline with the longer storage of the botulinum toxin (groups III and IV). These results support the authors' conduction study data, which suggest that the initial potency is not affected but the duration of action is. Again, groups I and II had comparable results. Microbiology cultures showed no growth of either aerobic or anaerobic bacteria at 7 days. In conclusion, using the rabbit model, it seems that reconstituted and stored botulinum toxin type A has the same initial potency but the duration of action is affected sometime after 2 weeks of storage. No bacterial contamination was associated with storing unpreserved reconstituted botulinum toxin type A for up to 12 weeks.