Spectrum of lymphoma subtypes based on the latest World Health Organization classification in southern Iran from 2000 to 2011.

Background: Lymphoma, both Hodgkin and non-Hodgkin, is one of the most common malignancies, with a distinct subtype distribution throughout the world. Methods: A total of 453 lymphoma cases, identified retrospectively from January 2000 to October 2011, were studied to identify the subtype distribution of lymphoma in our center, located in southern Iran, according to the latest WHO classification. Results: The most common sites of involvement of all lymphomas were extranodal (59.16%). The highest frequency of extranodal sites in all lymphoid neoplasms were associated with diffuse large B-cell lymphoma (22.95%) and classical Hodgkin lymphoma (10.15%). Of 453 cases, 23 (5.32%) were T and natural killer cell neoplasms, of which the most common subtypes were T-cell large granular lymphocytic leukemia and anaplastic large cell lymphoma. Conclusion: This study indicated that the subtype distribution of lymphoma (except for the higher prevalence of diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma and lower rate of follicular lymphoma) in this part of Iran is similar to that in the Middle Eastern countries. Mature B-cell neoplasms are less frequent compared with both western and far east Asian countries.

Zimmermann-Laband syndrome: Clinical and cytogenetic study in two related patients.

BACKGROUND: Zimmermann-Laband Syndrome (ZLS) is an extremely rare autosomal dominant congenital disorder. It is a craniofacial malformation syndrome with predominant intraoral involvement consisting of gingival fibromatosis diffusion in early development. The molecular basis of ZLS is still unknown. Although familial aggregation with different inheritance patterns is detected in ZLS patients, most of the cases are sporadic. MATERIAL AND METHODS: We report on two sibling patients with clinical manifestations of ZLS. Blood samples of both patients were obtained in EDTA-tubes followed by performing cytogenetic study using Cyto2.7M array. Analysis of the copy number was performed using the Chromosome Analysis Suite Software (version 1.0.1, annotation file na 30, Affymetrix) and interpreted with recourse to the UCSC genome browser (http://genome.ucsc.edu/; Human Mar. 2006NCBI Build 36.1/hg18 assembly). RESULTS: The array analysis revealed overlapping regions of chromosomal aberrations in both patients. We detected a 258-kb deletion at 3q13.13, a 89-kb duplication at 1q25.2 as well as two 67-kb duplications at 1p12 and 19q12. These altered regions do not contain any known genes and protein-coding sequences. CONCLUSIONS: In conclusion, the findings of this report revealed new chromosomal aberrations, including a deletion at 3q13.13 and duplications at 1q25.2, 1p12 and 19q12, in the two patients with ZLS. Such findings indicate that whole genome screening for genomic rearrangements is fruitful in typical and atypical patients with ZLS. Key words:Zimmermann-Laband syndrome, cytogenetic array, whole genome screening, chromosomal aberration, gingival fibromatosis.

Discrepancy of target sites between clinician and cytopathological reports in head neck fine needle aspiration: Did I miss the target or did the clinician mistake the organ site?

The diagnostic accuracy of fine needle aspiration cytology (FNAC) of head and neck lesions is relatively high, but cytologic interpretation might be confusing if the sample is lacking typical cytologic features according to labeled site by physician. These errors may have an impact on pathology search engines, healthcare costs or even adverse outcomes. The cytology archive database of multiple institutions in southern Iran and Australia covering the period 2001-2011, were searched using keywords: salivary gland, head, neck, FNAC, and cytology. All the extracted reports were reviewed. The reports which showed discordance between the clinician's impression of the organ involved and subsequent fine needle biopsy request, and the eventual cytological diagnosis were selected. The cytological diagnosis was confirmed by histology or cell block, with assistance from imaging, clinical outcome, physical examination, molecular studies, or microbiological culture. The total number of 10,200 head and neck superficial FNAC were included in the study, from which 48 cases showed discordance between the clinicians request and the actual site of pathology. Apart from the histopathology, the imaging, clinical history, physical examination, immunohistochemical study, microbiologic culture and molecular testing helped to finalize the target organ of pathology in 23, 6, 7, 8, 2, and 1 cases respectively. The commonest discrepancies were for FNAC of "salivary gland" [total: 20 with actual final pathology in: bone (7), soft tissue (5), lymph node (3), odontogenic (3) and skin (2)], "lymph node" [total: 12 with final pathology in: soft tissue (3), skin (3), bone (1) and brain (1)], "soft tissue" [total: 11 with final pathology in: bone (5), skin (2), salivary gland (1), and ocular region (1)] and "skin" [total: 5 with final pathology in: lymph node (2), bone (1), soft tissue (1) and salivary gland (1)]. The primary physician requesting FNAC of head and neck lesions are incorrect in their clinical impression of the actual site in nearly 0.5 percent of cases, due to the overlapping clinical and imaging findings or possibly due to inadequate history taking or physical examination.

Malignant adenomyoepithelioma of the breast: a review.

Malignant adenomyoepithelioma (MAME) of the breast is a rare lesion characterized by dual population of epithelial and myoepithelial cells which one or both components show malignant features. We report a case of MAME of the breast in a 46-year-old woman diagnosed by fine-needle aspiration with extensive review of the literature. Classification, clinical presentation, cyto-pathologic, and immunohistochemical features are described. This lesion showed both malignant components of epithelial and myoepithelial cells in cytology and histology. The malignancy was convincingly supported by high mitotic figures, pleomorphism, and invasion in tissue sections. This review of MAMEs showed that cyto-histologic diagnosis is difficult and should be supported by immunohistochemical study.

Spontaneous splenic rupture in melanoma.

Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin) confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic) rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

Molecular diagnosis and species identification of mucosal leishmaniasis in Iran and correlation with cytological findings.

OBJECTIVE: Mucosal leishmaniasis (ML) is a rare destructive disease that mainly affects the mucous membranes of the mouth and nose. The etiologic agent(s) of ML are not well known in the Middle East. STUDY DESIGN: Cytologic smears of ML from the mucosal lesions of 7 patients were prepared by scraping. In 2 patients with nasal lesions, exfoliative cytology was made by washing the nasal cavity. The smears were both air dried and fixed in alcohol and stained. Scrapings from the same smears were then tested for leishmanial DNA by nested PCR. RESULTS: This study characterized 9 isolates of ML, with 7 cases identified as Leishmania major and 2 as Leishmania tropica. While 6 patients were found to be positive by the cytology technique, the nested PCR was positive for all of these samples. CONCLUSIONS: Presence of granuloma and multinucleated giant cells in the negative smears of the patients who showed clinical manifestation of ML was an important clue for diagnosis of this disease. The PCR-based method not only appears to be a precise diagnostic approach in the identification of suspected cases of ML but is also efficient in determining the species of the parasite. L. major and L. tropica can lead to ML, but they result in different cytologic features.

Problem of foreign body in GI tract.

Most foreign bodies pass through the gastrointestinal tract uneventful. We report of a case of inadvertently ingested foreign body, which by endoscopy simulated a polyp and on biopsy reported as cancer, so the patient underwent an unnecessary major operation. This report emphasizes the importance of resemblance of foreign bodies with gastrointestinal neoplasm, and endoscopists, surgeons and pathologists should consider this entity in their daily practice.

Clinical, histopathologic, and cytologic diagnosis of mucosal leishmaniasis and literature review.

CONTEXT: Mucosal leishmaniasis (ML) is a rare disease in the world, even in endemic areas such as Iran. Clinical, histologic, or cytologic assessment may help in the diagnosis of ML. OBJECTIVE: To describe clinical, histologic, and cytologic findings in ML. DESIGN: Review of our files showed 11 patients diagnosed with ML, of whom 7 patients had oral lesions, 1 of whom was a known patient with oral leishmaniasis with recurrence of oral lesions; 2 had laryngeal lesions; and 3 had nasal lesions. One case of laryngeal leishmaniasis was a recurrence of prior oral lesions. Cytologic smears were prepared by scraping the lesions with a scalpel or cytobrush. Histology on the biopsies was done for 7 patients. In 2 patients with nasal lesions, exfoliative cytology was made by washing the nasal cavity. Smears were both air dried and fixed in alcohol and stained. RESULTS: Cytologic findings showed free Leishman-Donovan bodies, intrahistiocytic Leishman-Donovan bodies, atypical organisms, granuloma, acute and chronic inflammatory cells, histiocytes, multinucleated giant cells, mast cells, binucleated histiocytes (Reed-Sternberg-like cells), and plasma cells. In 6 of the patients, biopsy was inconclusive and in subsequent cytology the organism was detected. In 3 cases, findings from clinical and cytologic examinations were suggestive for leishmaniasis; however, with response to treatment, the diagnosis was confirmed. In 5 patients a malignant tumor was suspected because of clinical or histologic findings, but cytology helped to diagnose leishmaniasis. CONCLUSIONS: Clinically or histologically, ML can be mistaken for benign and malignant lesions. Scraping or exfoliative cytology is an easy, reliable, and cost-effective method for diagnosing ML. Thus, clinical, histologic, and cytologic features together may help in ML diagnosis.

Primary bilateral Burkitt lymphoma of the lactating breast: a case report and review of the literature.

Burkitt lymphoma (BL) is a highly aggressive neoplasm, which frequently affects the ileocecal region in the sporadic form and the jaw in the endemic form; however, the breast is a rare primary site of this tumor. Here we describe a case of primary bilateral breast BL presenting during lactation in a 23-year-old woman. Excisional biopsy of breast masses demonstrated a B-cell lymphoma with a characteristic 'starry sky' pattern highly suggestive of BL. The neoplastic cells strongly expressed CD20 and CD10, and showed proliferative activity as measured by Ki-67. An IGH-MYC gene fusion indicating the presence of a typical Burkitt translocation t(8;14)(q24;q32) in the tumor tissue was detected by fluorescent in situ hybridization. The present case, along with a comprehensive review of the literature, demonstrates that BL of the breast should be considered in the differential diagnosis of lesions of the breast during lactation. Whether hormonal or antigenic factors trigger Burkitt lymphomagenesis in the lactating breast warrants further investigation.

Preoperative washing cytology in the diagnosis of maxillary sinus lesions.

OBJECTIVE: To assess the preoperative value of washing cytology in maxillary sinus lesions with suspected malignancy. STUDY DESIGN: Over a 4-year period, 96 p tients with clinical or radiologic suspicion of a malignant maxillary sinus tumor either confined to the maxillary complex or extending to the nasal cavity underwent preoperative cytologic evaluation by sinus puncture and local washing or nasal washing. Subsequently all patients underwent endoscopic sinus surgery (ESS) and partial or total maxillectomy. For controls, 10 patients with rhinosinusitis, who according to standard symptoms and radiologic scores, were candidates for ESS, washing cytology and subsequent random mucosal biopsy were used. RESULTS: There were 47 malignant, 42 benign and 7 borderline cases. Benign lesions included inflammatory conditions (17), squamous proliferations (6), soft tissue lesions (9) and odontogenic lesions (10). Borderline lesions included hemangiopericytoma (4) and ameloblastoma (3). Malignant lesions included squamous cell carcinoma (8), sinonasal adenocarcinoma (2), salivary gland tumors (4), soft tissue tumors (18), malignant melanoma (8) and hematolymphoid neoplasms (7). The overall sensitivity, specificity, positive predictive value and negative predictive value of preoperative washing cytology were 88.6%, 88.2%, 86.6%, 90%, respectively. Diagnostic agreement between cytology and follow-up biopsy was seen mostly in benign inflammatory and odontogenic lesions and in squamous cell carcinoma and salivary gland malignancies. CONCLUSION: Preoperative sinus washing cytology is a noninvasive and rapid method of diagnosis, with a definite impact on patient surgical planning. Clusters of sloughed epithelial cells, so called Creola bodies, may be a diagnostic pitfall in benign lesions.

Bone marrow aspiration findings in kala-azar.

OBJECTIVE: To describe the bone marrow aspiration cytologic findings in visceral leishmaniasis. STUDY DESIGN: Bone marrow aspiration of 204 documented cases of kala-azar were reviewed in order to find aspiration clues other than typical intrahistiocytic and free Leishman-Donovan bodies. Aspiration findings were divided into different groups of common, uncommon as well as atypical/unusual findings. RESULTS: Common findings were granulomas, intrahistiocytic and free typical organisms, plasma cells with or without inclusions, eosinophilia, free floating cytoplasmic bodies with or without Leishman bodies, granular bodies and erythroid hyperplasia. Uncommon findings were: intracellular (non-histiocytic) organisms, hemophagocytosis, plasma cells with abnormal crystalline inclusions, leukemic blasts and necrosis. Atypical/unusual findings were: spore-like organisms, regular or irregular shape of aggregates of organisms (flower-like, ball-like, rosette-like, doughnut-like and platelet-like), intracytoplasmic granule-like organisms (kinetoplast only), pseudo-Pelger Huet, increased vessels, fibroblasts, Reed-Sternberg-like cells, multinucleated giant cells, tart cells and foamy cells. CONCLUSION: Knowledge of common, uncommon and unusual/atypical bone marrow aspiration findings of kala-azar may help arrive at a correct diagnosis; avoid unnecessary workups, such as sophisticated molecular techniques; and avoid fatal outcomes in untreated or non-diagnosed cases.

Diagnostic difficulties in the interpretation of fine needle aspirate samples in salivary lesions: diagnostic pitfalls revisited.

OBJECTIVE: To present our experience in diagnostic errors and pitfalls on aspiration cytology of salivary region in a high volume of cases. STUDY DESIGN: In a retrospective review of cytology files of a head and neck referral center from 1990 to 2005, the false positive and false negative interpretations on fine needle aspiration (FNA) of salivary lesions were retrieved. These records and slides were reviewed to identify cytologic characteristics that contributed to false diagnosis. RESULTS: Of a total of 1,040 salivary FNA samples, 376 cases had a final histologic diagnosis with interpretations of benign or malignant. The sensitivity and specificity for correct interpretation of benign and malignant were 87% and 96%, respectively. The most common false negative cases were acinic cell carcinoma, epithelial myoepithelial carcinoma, adenoid cystic carcinoma and basal cell adenocarcinoma. Benign cases with false positive diagnosis were Warthin tumor and pleomorphic adenoma. Selected positive and negative discordant cases are also discussed. CONCLUSION: Knowledge of cytologic overlaps and pitfalls on salivary gland FNA, as well as clinical and radiologic features, may help clinicians arrive at the appropriate diagnosis and reduce false interpretations. Several clinically important pitfalls with nonsalivary tumors of jaw and skin are demonstrated in our series.

Cytologic differentiation of struma ovarii from other ovarian neoplasms.

OBJECTIVE: To present the cytologic findings of struma ovarii and value of cytology and immunocytochemistry (ICC) using thyroglobulin (TGB) and thyroid transcription factor-1 (TTF-1) in evaluation of this unusual ovarian neoplasm, together with the diagnostic pitfalls. STUDY DESIGN: Intraoperative cytologic findings of 7 patients with struma ovarii are reviewed. Cytologic material of both cystic and solid components was collected intraoperatively. ICC staining was done, and cell block preparation performed on selected cases. RESULTS: The cases were divided in to 3 groups: group 1--diagnosis of struma ovarii was made by cytology and confirmed by ICC (1 case); group 2--diagnosis was suggestive on cytology or cell block and confirmed by ICC staining (4 cases); group 3--on cytologic diagnosis indistinguishable from other cystic ovarian neoplasms (2 cases). Cytologic findings were typically colloid with mosaic pattern, follicles, follicular cells only, sheets of follicular cells, both colloid and follicular cells, proteinaceous background or degenerated epithelial cells indistinguishable from other cystic ovarian neoplasms. CONCLUSION: Cytologic findings of struma ovarii are distinct enough to be suggested intraoperatively, and ICC for TGB or TTF-1 is a valuable tool for preoperative fine needle aspiration biopsy and intraoperative diagnosis of this benign ovarian neoplasm.

New cytologic clues in localized Leishmania lymphadenitis.

OBJECTIVE: To describe new cytologic clues to diagnose localized leishmania lymphadenitis (LLL). STUDY DESIGN: The study examined cytologic smears of 170 cases of LLL referred to our department from November 1989 to October 2004. A total of 120 cases were confirmed by detecting Leishman-Donovan (LD) bodies in at least 1 of the cytologic smears and 50 cases, which were histologically confirmed. For comparison we studied cytologic smears of 20 cases of tuberculous lymphadenitis, 20 cases of toxoplasma lymphadenitis and 20 cases of granulomatous lymphadenitis of unspecified causes. RESULTS: Cases were divided into 4 major groups. Cytologic findings in these groups were studied to find highly suggestive clues. Cytologic findings present in most of these groups, but absent or very rare in other granulomatous lymphadenitis, were LD kinetoplasts, plasma cells with different shapes of inclusions and lymphogranular bodies. Rare findings not reported previously were: intraneutrophilic LD bodies, hematoxylin body-like inclusions, fibroblasts, cytoplasmic blebbing and floating parasitophorous vacuoles. CONCLUSION: Despite previous reports emphasizing detecting LD bodies in diagnosing LLL, we present cytologic clues highly suggestive of this self-limited disease when LD bodies cannot be detected or are very few on the smears.