Treatment results in advanced stage Hodgkin's lymphoma: a retrospective study.

BACKGROUND: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. AIM: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. MATERIALS AND METHODS: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. RESULTS: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. CONCLUSIONS: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

Pathological complete response in locally advanced breast cancer: determinants and predictive significance.

BACKGROUND: Neoadjuvant chemotherapy is now the standard approach for most large breast cancers including locally advanced cancers of the breast. The majority of patients respond satisfactorily to chemotherapy with effective downsizing of tumours to consider breast conservation surgery. Pathological complete response (pathCR) is known to be a strong predictor of good outcome; however, many factors are known to influence the extent of response to chemotherapy. It has been observed that smaller the tumour, better is the response achieved in contrast to larger and locally advanced tumours where only one-third may respond well enough to merit breast conservation. Various other clinical, biological and molecular factors are also being evaluated as effective predictors of chemosensitivity. Most of these are either not easily available for all patients in developing countries or are overtly expensive and not applicable for all patients. METHODS: We evaluated the clinical and pathological predictors of response to chemotherapy in 1402 women with locally advanced breast cancer. RESULTS: There was a higher rate of pathCR in smaller tumours, younger women and ER-negative as well as triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and lymphatic and vascular invasion (LVI) were associated with lower pathCR. CONCLUSION: In the absence of ready availability of expensive molecular and genomic assays, clinical parameters and standard histopathological variables can also be useful indicators of response to neoadjuvant chemotherapy. Additionally, they can help identify those who could be eventually conserved or have a better outcome.

Can We Avoid Axillary Lymph Node Dissection (ALND) in Patients with 1-2 Positive Sentinel/Low Axillary Lymph Nodes (SLN/LAS+) in the Indian Setting?

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Non-Hodgkin's lymphoma of Waldeyer's ring in children: outcome using chemotherapy and involved field radiotherapy.

AIM: To evaluate the prognostic factors and treatment outcome of children with non-Hodgkin's lymphoma (NHL) of Waldeyer's ring treated at a single institution. MATERIALS AND METHODS: Thirty-two children with NHL of Waldeyer's ring treated at our institute between January 1990 and December 2001 were included in this analysis. The median age at presentation was 14 years, and most of the patients (87%) were boys. The most common histological subtype was diffuse large B-cell lymphoma (75%), 25% patients had stage I and 75% had stage II disease. Treatment comprised a combination of chemotherapy and radiotherapy in most of the patients (75%). Among these patients, 71% received a radiotherapy dose of > or = 45 Gy. RESULTS: After a median follow-up of 45 months, the 5-year disease-free and overall survival rates were 76.5 and 83.2%, respectively. Age > 10 years (P = 0.032), bulky tumours (P = 0.001) and the presence of B-symptoms (P = 0.004) had a negative influence on disease-free survival. Patients treated with a combination of chemotherapy and radiotherapy had a better outcome than patients treated with chemotherapy alone (disease-free survival: 87.1% vs 56.2%, P = 0.056). The complete response (P = 0.003), disease-free survival (P = 0.001) and overall survival (P = 0.001) rates were significantly better for patients receiving a radiotherapy dose > or = 45 Gy. CONCLUSION: The age at diagnosis, the size of the tumour, and the presence of B-symptoms significantly influenced the outcome of children with NHL of Waldeyer's ring in this study. A combined modality treatment, comprising chemotherapy and radiotherapy, resulted in a satisfactory outcome in patients with this rare neoplasm.

Morphological spectrum of AIDS-related plasmablastic lymphomas.

We have had a recent spurt in cases of AIDS-related lymphoma (ARL) at our centre. Most of these cases are aggressive mature B cell lymphomas, mainly plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL). Most of the PBL are extranodal in location and are mucosa-based. We reviewed the morphological features of 34 cases of PBL. Diagnosis was based on morphology, immunohistochemistry, proliferation index, HIV positive status and its preference to extranodal sites (mostly mucosa based). We classified PBL into three morphological subtypes (immunoblastic - 25, Burkitt's - 7, plasmacytic - 2). Tumor cells expressed as leucocyte common antigen (LCA) in 60%, CD138 in 100%, EMA in 45% and light chain restriction in 86% cases. CD20 was negative in all cases. Pathologists need to be aware of PBL and its various morphological subtypes as the identification of this entity from its close differentials carries major therapeutic implications.

A clinicopathologic study of mantle cell lymphoma in a single center study in India.

We present clinical features, histopathology and results of treatment in cases of mantle cell lymphoma (MCL) at our hospital. We had 93 cases (2.1%) of MCL out of total 4301 cases of non-Hodgkin's lymphoma (NHL) in a 4-year period. It included 68 cases (1.7%) of MCL from 3987 cases of NHL diagnosed on histopathology. Remaining 25 cases (7.9%) diagnosed solely on peripheral blood examination were excluded. Thirty-six (85%) patients had advanced-stage disease. Sixty-three were nodal and five were extranodal (all gastrointestinal tract). Common patterns were diffuse (64%), nodular (25%) and mantle zone type (11%). Sixty-two cases had lymphocytic while six had blastic morphology (all nodal). Tumor cells expressed CD20 (100%), CD43 (94%), CD5 (89%) and cyclin D1 (85%). Bone marrow was involved in 25 (59%) cases. Thirty-two patients could be treated. Median recurrence-free survival was 22.23 months. Diffuse pattern of nodal involvement had a lower overall survival.

Anaplastic large cell lymphoma (ALCL) presenting as primary bone and soft tissue sarcoma--a study of 12 cases.

This study highlights the rare presentation of anaplastic large cell lymphoma as primary bone and soft tissue tumour. Twelve cases were studied. Clinical impression was non Hodgkin's lymphoma in 4 cases, sarcoma in 6 (osteosarcoma-2, Ewing's/primitive neuroectodermal tumour-1, and sarcoma NOS-3), and tuberculosis of thoracic spine in 1 and the last case involving the rib had a differential diagnosis of tuberculosis and NHL. Histology revealed round cells with eosinophilic cytoplasm and pleomorphic nuclei. Immunohistochemically all tumours were CD30 positive and 8 of 9 cases (88.9%) showed ALK-1 positivity. The pleomorphic cytomorphology ofALCL leads to confusion with the more frequent bone and soft tissue sarcomas affecting the musculoskeletal system. A high index of suspicion is necessary to initiate the correct panel of immunohistochemical markers to first confirm the lymphomatous nature of this tumour and to subsequently subclassify. This alone will lead to an accurate recognition of ALCL and the appropriate chemotherapy.

Predicting loco-regional recurrence risk in T1, T2 breast cancer with 1-3 positive axillary nodes postmastectomy: Development of a predictive nomogram.

BACKGROUND: Role of postmastectomy radiotherapy (PMRT) in early breast cancer with 1-3 positive axillary nodes is still controversial. Hence, there is a need to identify subgroup of patients who have sufficiently high risk of disease recurrence to benefit from PMRT. AIM: The aim is to evaluate clinical outcomes of patients postmastectomy having pathological T1-T2 tumors with 1-3 positive axillary lymph nodes (LNs) treated with adjuvant systemic therapy and develop a predictive nomogram. MATERIALS AND METHODS: Data collected retrospectively from eligible patients from 2005 to 2011. Kaplan-Meier survival analysis was used for all time-to-event analysis. Various known clinical and pathological risk factors were correlated with outcome using uni- and multi-variable analysis in SPSS version 21. All comparisons were two-tailed and P < 0.05 were considered statistically significant. The nomogram to predict the risk of loco-regional control (LRC) was developed using least absolute shrinkage and selection operator shrinkage model in hdnom.io software. RESULTS: 38/242 (15.7%) patients had recurrent disease at loco-regional (10 patients), distant sites (22 patients) and simultaneous loco-regional and distant sites (6 patients) at a median follow-up 59.5 (range 4-133) months. Five years estimate of LRC, distant disease-free survival (DFS), DFS, cause-specific survival and overall survival was 87.8%, 85.4%, 84.2%, 93.1%, and 91.5%, respectively. Pathological tumor size, margin status, LN ratio as continuous variables and grade and triple negative breast cancer status as categorical variables were the risk factors included in the model for building nomogram. CONCLUSION: The nomogram developed based on institutional data can be a valuable tool in guiding adjuvant PMRT depending on the risk of 5 years loco-regional recurrence.

Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma: treatment outcome and prognosis.

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is one of the extremely rare variants of papillary thyroid carcinoma. To date, the majority of reported cases have been published in the surgical pathology and cytopathology literature, addressing the diagnostic difficulties posed by the condition's extensive, reactive stromal proliferation. Because of the rarity of PTC-NFS among papillary thyroid carcinoma variants, it has been unexplored from a clinical viewpoint. A MEDLINE search on the clinical course, role of radioiodine, treatment outcome and long term follow up of this disease yielded no result.We report the clinicoradiologic and histopathologic profile, together with post-treatment long term follow up, in a 35-year-old woman harbouring this rare entity. To the best of our knowledge, this is the first report of a five-year follow up of this rare variant of PTC following total thyroidectomy and radioiodine treatment. Our follow-up findings reiterate the disease's favourable clinical course when managed in the same manner as a classical, differentiated papillary carcinoma of the thyroid, akin to that predicted by the pathologists, and emphasize the importance of differentiating PTC-NFS as a separate entity from the papillary carcinoma variants with aggressive histology. Given the rarity of this condition, the experience gained from the present case is a useful addition to the current knowledge on disease prognostication and management.A systematic review of the existing literature on PTC-NFS, including the case reported in the present paper, is also carried out, aiming to explore the patient characteristics and clinical behaviour pattern of this rare entity and to make appropriate recommendations on management strategy. The age of presentation ranges from 20 to 82 years, with a mean of 44.5 years. Female preponderance was observed, with a female to male ratio of 3ratio1. No racial predilection was observed. Tumour size varied from 2 to 9 cm along its greatest diameter (mean = 4.3 cm). Metastasis to lymph nodes at presentation occurred in 25 per cent of cases. Metastasis to surrounding structures (e.g. parathyroid and skeletal muscle) was observed in 12.5 per cent. There have been no reports of pulmonary or skeletal metastasis at presentation.

Cytologic diagnosis of a melanotic neuroectodermal tumor of infancy occurring in the cranial bones.

Melanotic neutroectodermal tumor of infancy (MNTI) is a rare, usually benign tumor commonly occurring in the maxilla. MNTIs at unusual sites like the cranium clinically mimic malignant small round cell tumors. Consequently, a correct preoperative cytologic diagnosis of MNTI at these sites helps in the surgical management of the patient. We report on a cytologically diagnosed case of MNTI in the frontotemporal region of the skull in an infant. Aspirates from the lesion were cellular, with a bimodal population mainly of small neuroblast-like cells admixed with a few large epithelioid cells with melanin granules. In the present case, following the cytologic diagnosis a wide local excision was carried out, and the histologic examination confirmed the cytologic diagnosis. Diagn. Cytopathol. 1999;21:280-283.

Aspiration cytology in the diagnosis of primary tumors of skin adnexa.

OBJECTIVE: To evaluate the cytologic features and pitfalls in the cytodiagnosis of certain tumors of skin adnexa. STUDY DESIGN: Smears from five nodular basal cell carcinomas, two chondroid syringomas and one case each of primary mucinous carcinoma, Merkel cell tumor, trichoepithelioma, pilomatrixoma and eccrine spiradenocarcinoma, all histologically confirmed, were evaluated with special attention to cytologic features that may aid the diagnoses. RESULTS: Ten of 12 (83.3%) adnexal tumors were correctly recognized on aspiration cytology. The five basal cell carcinomas were atypical in presentation and clinically unsuspected but were diagnosed on cytology. The chondroid syringomas and Merkel cell tumor could also be diagnosed due to awareness of the cytologic features and sound clinical correlation. The eccrine spiradenocarcinoma was diagnosed as spiradenoma because of improper assessment of local invasion and incorrect mitotic count in the aspirates. The diagnosis was inaccurate in primary mucinous carcinoma as the aspirate yielded mainly mucin. CONCLUSION: Although exact subtyping of tumors of skin adnexa may not always be essential, certain benign adnexal tumors have aggressive counterparts (e.g., eccrine spiradenomas), while others clinically mimic metastases or small round cell carcinomas (e.g., Merkel cell tumors). Thus, correct cytodiagnoses and awareness of the limitations of cytology (such as in the assessment of local invasion) in these instances help to outline surgical management.

Cystic degeneration in phyllodes tumor. A source of error in cytologic interpretation.

OBJECTIVE: To examine problems encountered in the cytologic interpretation of phyllodes tumor (PT) with cystic degeneration and solutions thereof. STUDY DESIGN: Cystic degeneration was found in seven PTs (five benign, one low grade and one high grade). Aspirates from these yielded fluid and were usually labelled fibrocystic change on the original cytology. Smears were retrospectively analyzed, with special attention to the background, presence and nature of the epithelial and stromal fragments, foam cells and naked nuclei in the background. RESULTS: PTs with cystic degeneration on cytology showed thick fluid in the background, foamy macrophages (100%), apocrine cells (28%) and epithelial fragments, which showed nuclear atypia in two cases. On reviewing the smears, five of seven PTs had stromal fragments, albeit in small numbers. Most important, even in the absence of stromal fragments, all cases showed 5-50% naked nuclei of the fibroblastic type dispersed within the fluid background. CONCLUSION: In cases of fluid aspirates from well-defined lumps, one must search for fibroblastlike naked nuclei or stromal fragments within the fluid to clinch the diagnosis of phyllodes tumor.

Aspiration cytology of tubular adenomas of the breast. An analysis of eight cases.

OBJECTIVE: To analyze fine needle aspirates from tubular adenomas of the breast and elucidate cytologic features unique to these tumors. STUDY DESIGN: Fine needle aspiration (FNA) cytology smears from eight tubular adenomas were reviewed, with special attention given to architectural features and individual cell characteristics. Smears were then compared with those from 25 fibroadenomas and 2 tubular carcinomas for analyzing the distinguishing features. RESULTS: Aspirates from tubular adenomas revealed cells arranged as small, three-dimensional balls or clusters, tubules of different shapes and less frequently as closely approximated acini. Cells were uniform, with pale cytoplasm, which showed magenta granules in the Giemsa smears from two tumors. Straight tubules, closely approximated acini and intracytoplasmic granules were not seen in aspirates from fibroadenomas. The tubules in tubular adenomas always showed myoepithelial cells and were more open than the angulated tubules of tubular carcinoma. CONCLUSION: Tubular adenomas on FNA cytology specifically show cells arranged as small, three-dimensional balls, tubules or closely approximated acini. Cells are uniform and sometimes show intracytoplasmic granules in Giemsa-stained smears.

Fine needle aspiration of tophi for crystal identification in problematic cases of gout. A report of two cases.

BACKGROUND: The definitive diagnosis of gout is best established by demonstration of monosodium urate (MSU) crystals in the synovial fluid or biopsy. Fine needle aspiration cytology (FNAC) of tophi can play a crucial role in diagnosis. CASES: A 36-year-old chronic alcoholic male developed subcutaneous nodules on both malleoli without a history of arthropathy and with normal serum uric acid levels. FNAC of the nodules demonstrated stacks and sheaves of needle-shaped crystals of MSU. A 50-year-old diabetic male developed multiple nodules on the feet. He gave a past history of painful athropathy. A roentgenogram of the feet was suspicious for gout; however, joint aspiration failed, and the serum uric acid levels were normal. At this juncture FNAC of the feet tophi clinched the diagnosis of gout. In both cases, polarization of needle washings (wet mount) and the fixed, Papanicolaoustained smears showed negatively birefringent, needle-shaped crystals of MSU, thus confirming the diagnosis of gout. CONCLUSION: FNAC of gouty tophi is an easy alternative to synovial biopsy and joint fluid analysis. It is simpler, easier and less painful. As crystals are preserved in stained smears, they can be employed for polarization and confirmation of gout.

Cytodiagnosis of simple and proliferating trichilemmal cysts.

OBJECTIVE: To elucidate the cytologic findings in simple trichilemmal (pilar) cysts and proliferating trichilemmal cysts (pilar tumors) and the clinical importance of these lesions. STUDY DESIGN: Aspirates from 12 simple pilar cysts and three pilar tumors, all histologically confirmed, were analyzed with a view to elaborating on specific cytologic features enabling a distinction from epidermal cysts and other adnexal tumors. RESULTS: Aspirates from pilar cysts showed two different pictures, depending on the age of the cyst. Young pilar cysts showed aspirates with an abundant background of blotchy keratin with or without calcification and inflammation. Older (degenerating) cysts showed oily fluid debris with cholesterol crystals and inflammatory cells. The epithelial component was sparse, and only an occasional syncitial cluster of small squamoid cells was seen. As opposed to this, epidermal cysts usually showed a cleaner background, with very cellular aspirates containing many nucleate and anucleate squames, keratin flakes, platelike crystals and no calcification. The pilar tumors showed a lesser amount of keratin as compared to pilar cysts and yielded large and small clusters of squamoid and basaloid cells, a few of which showed an abrupt association with anucleate, keratinized globules. CONCLUSION: The cytologic diagnosis of a pilar cyst should be made especially in scalp cysts, which yield either abundant, blotchy keratin or oily, cholesterol-rich debris with a sparse epithelial component and which lack a mixture of anucleate and nucleate squames. On aspiration, pilar tumors yield comparatively more cells and less keratin and show small, basaloid or squamoid cells abruptly associated with keratin globules. The cytologic diagnosis of pilar cysts is important because these cysts recur if incompletely excised and often undergo transformation to pilar tumors. Similarly, pilar tumors often clinically mimic squamous carcinomas, and hence there is a need to outline definitive cytologic features.

Mucin histochemistry of esophagus in health and malignancy.

AIMS: To study mucin histochemistry of the normal esophagus, esophageal adenocarcinoma, and carcinoma exhibiting glandular and squamous elements, to ascertain the origin of these tumors. METHODS: Mucin histochemistry was studied in sections of the normal cardioesophageal junction obtained from 25 post-mortem specimens and in 12 mucin-secreting esophageal carcinomas. RESULTS: The normal submucosal esophageal glands and three adenocarcinomas secreted predominantly sulfomucins; a mixture of neutral and sialomucins was seen in the nine carcinomas with squamous and glandular traits. Barrett's metaplasia was not encountered. CONCLUSIONS: In the absence of Barrett's metaplasia, esophageal adenocarcinoma probably arises from the submucosal glands, whereas squamous carcinomas with mucin-secreting component could arise from metaplastic change in squamous epithelium, cardiac glands, or multipotent stem cells in the epithelium.

Gastric carcinoma presenting as solitary cutaneous metastasis.

We report a patient with gastric adenocarcinoma presenting with a cauliflower-like large papillomatous cutaneous metastases on the nape of the neck.

Intracranial subfrontal schwannoma treated with surgery and 3D conformal radiotherapy.

Subfrontal schwannoma not arising from the cranial nerves are rare tumors. A 19-year-old man presented with a large subfrontal extra-axial enhancing mass with a preoperative diagnosis of skull base meningioma. A subtotal resection of the tumor mass was carried out. Microscopic examination revealed it to be a schwannoma. The residual tumor was treated with fractionated three-dimensional conformal radiotherapy (3D CRT). The rationale of treating with radiotherapy in such cases is analyzed.