Dear Editor,

Re: Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma

We read with interest the article by Carr NJ et al (J Clin Pathol 2009;62:516-518). The article describes the prevalence of different colorectal polyps in an unselected population with a focus specifically on sessile serrated adenomas (SSAs) and their correlation with BRAF mutation.

We found the most striking result in this paper presented in Table 1. SSAs (as defined by the authors) were predominantly seen in the right side of the colon (51 on the right and 6 on the left; a ratio of almost 9:1). This result is all the more emphasized by the fact that not all the patients had full colonoscopy. However, the authors failed to highlight this important result and ultimately reported that serrated polyps were more likely to be left-sided. This observation of a right-sided predominance of SSAs is in agreement with many other publications(1, 2). The finding of more right-sided SSAs have been reported to correlate with the higher number of serrated adenocarcinomas found in the right colon in other studies(3).

Also, the authors over-emphasize the prevalence of SSAs, concluding that they are seen ‘commonly in routine endoscopy practice’. The SSAs accounted for 11% of all serrated lesions and only 3.9% of all polyps in this study and such low percentages cannot and should not be reported as being encountered commonly in routine practice.

In addition, use of Student’s t test to analyse the relationship between polyp type and age may have been inappropriate given the most likely non-normal distribution of data, especially with the small numbers in the polyp subgroups. A non-parametric statistical test would have been more appropriate.

Olorunda Rotimi, FRCPath, PGDip Health Research, Georgina Reall, FRCPath

References

1. Higuchi T, Sugihara K, Jass JR. Demographic and pathological characteristics of serrated polyps of colorectum. Histopathology 2005;47:32–40.

2. Amy E. Noffsinger. Serrated Polyps and Colorectal Cancer: New Pathway to Malignancy. Annual Review of Pathology, Mechanisms of Disease 2009;4:343–64.

3. M. J. Makinen, S. M. C. George, P. Jernvall, J. Makela, P. Vihko and T. J. Karttunen. Colorectal carcinoma associated with serrated adenoma - prevalence, histological features, and prognosis. Journal of Pathology 2001; 193: 286-294

Department of Histopathology St James's University Hospital Leeds, UK

Dear Editor,

Dr. Aslam presented a rare case with peritoneal lymphomatosis and concluded that a histologic examination is crucial in the diagnosis, while cytology might sometimes mislead the workup.1 However, we present here another such case with raised CA 125 and demonstrate that cytology with a flow cytometry examination can help in the diagnosis.

This 44-year-old female suffered from autoimmune disorder and had been using steroids for several months. She was admitted to our ward due to progressive abdominal fullness, back soreness and shortness of breath. An abdominal echo revealed a pelvic mass with ascites. A computed tomography (CT) scan showed bilateral ovarian masses and multiple lymphadenopathies over the pelvic, abdominal and retroperitoneal areas. Biomarkers including CEA, SCC, AFP, CA 199, CA 153 were all within normal range except for a raised CA 125 level (125.27 U/ml, normal range 2.4~36.6 U/ml).

Ascitic fluid showing a turbid appearance was aspirated and sent for cytologic and microbiologic studies, however no micro-organisms grew from the culture. The cytologic study revealed massive lymphocytes with bizarre morphology. Flow cytometry was used to determine the characteristics of the cells, and showed positive for CD10, CD19, CD20, and negative for CD7.

Under the impression of suspected lymphoma with peritoneal lymphomatosis, CT guided biopsy of the lymph node was done. The resulting histology examination revealed a diffuse large B cell lymphoma which was positive for LCA, CD20 and negative for cytokeratin and CD7 (fig 1). She received systemic chemotherapy with R-CEOP regimen, but unfortunately died of sepsis.

Peritoneal lymphomatosis is a rare manifestation of malignant lymphoma. Although there are some criteria that tell the difference of peritoneal lymphomatosis from carcinomatosis, most of the cases are indistinguishable from the clinical presentations and image studies.2,3 Even the tumor markers, such as a raised CA 125 as in this case, cannot rule out the diagnosis of peritoneal lymphomatosis completely.4 These factors stress the importance of putting lymphoma into the list of diagnoses in such patients. We also highlight the important role of cytology examinations with flow cytometry, which might also help the physician in the diagnosis of peritoneal lymphomatosis and avoid unnecessary studies and treatment.

Hui-Hua Hsiao,^{1, 2} Yi-Chang Liu,^{1, 2} Jui-Feng Hsu,¹ Sheng-Fung Lin^1,2

1 Faculty of Medicine, College of Medicine, Kaohsiung Medical University; and

2 Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Correspondence to: Dr SF Lin, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100, Tzu-You 1st Road, Kaohsiung 801, Taiwan. E-mail: shlin@cc.kmu.edu.tw

Competing interests: none

REFERENCES

1. Aslam MB. Peritoneal lymphomatosis, a morphological look alike to peritoneal carcinomatosis: a autopsy report. J Clin Pathol 2009;62:480.

2. Kim Y, Cho O, Song S, et al. Peritoneal lymphomatosis: CT findings. Abdom Imaging 1998;23:87-90.

3. Karaosmanoglu D, Karcaaltincaba M, Oguz B, et al. CT findings of lymphoma with peritoneal, omental and mesenteric involvement: Peritoneal lymphomatosis. Eur J Radiol 2008; in press

4. Horger M, Muller-Schimpfle M, Yirkin I, et al. Extensive peritoneal and omental lymphomatosis with raised CA 125 mimicking carcinomatosis: CT and intraoperative findings. Br J Radiol 2004;77:71-3.

FIGURE LEGEND

Diffuse infiltration of medium-sized, monotonous round cells with hyperchromatic nuclei and scant cytoplasm (H&E stain, x400). Upper right: Positive CD20 reaction to the lymphoma cells and no reaction to endothelial cells.

Dear Editor

Warthin tumor (WT) of the salivary gland (so called papillary cystadenoma lymphomatosum or adenolymphoma) is a benign neoplasm of the salivary gland epithelium with a proliferative epithelial component associated with a variably prominent stroma.[1] As reported by Saxena [1], histogenesis of this entity is very controversial. WT and malignant lymphoma are rarely associated, and most are examples of involvement of the lymphoid stroma of WT by a disseminated lymphoma.[1] Less commonly, malignant lymphomas are first detected in the lymphoid stroma of WT.[1] Most of reported cases are low-grade follicular lymphoma.[2] To the best of our knowledge no well-documented cases of nodal marginal B-cell lymphoma arising from WT in the same site have been described so far.

We report the case of a 74-year-old man with a fast enlarging right parotid mass. On physical examination the mass was firm, painless, developed in the lower pole of the parotid gland. A partial parotidectomy was performed. At gross examination, the tumour measured 4.2 x 3.1 x 1.7 cm and cut surface revealed an irregular, brown mass replacing parotid gland. Histologically, the tumour was composed of cystic spaces with typical bilayered oxyphilic epithelium.(Figure 1A) This epithelium was surrounded by malignant lymphoma characterized by diffuse infiltrate of small to medium lymphoid cells composed of centrocyte-like B-cells, plasmocytoid B-cells, scattered centroblast and immunoblast-like cells.(Figure 1B) No germinal center, lympho-epithelial lesion or necrotic areas were observed. The immunohistological study demonstrated a phenotypical profile (CD20/CD79a/BCl-2+; CD3/CD5/CD10/CD21/cycline D1-) consistent with marginal zone B-cell lymphoma. (Figure 1C, D)

On the basis of morphological and immunohistological findings, a diagnosis of nodal marginal zone B-cell arising of WT's lymphoid stroma was established. A thorough staging examination, including cervical, thoracic and abdominal scans revealed no evidence of other peripheral lymph nodes involvement. All laboratory test results were normal except a small monoclonal serum protein and mild lymphocytosis which slowly increased since 2004. The immunophenotypage showed a monotypic B-cell lymphoid population with moderate Lambda light chain expression. No bone marrow biopsy was done. Because of localised disease, no treatment was started. At this time, the patient has been followed-up for 21 months, without evidence of recurrent tumoral syndrome.

Distribution of WT localization (parotid glands and periparotid lymph node and its absence from other salivary tissue lacking incorporated lymph node) seems to show that WT's histogenesis results from heteropic salivary ductal inclusions in intra- or peri-parotid lymph nodes.[3] This theory explains that most lymphomas arising of WT are follicular lymphomas, which are the most frequent of systemic lymphomas.[4] No marginal zone B-cell lymphoma arising of WT was yet reported. Only one case reported in the same parotid gland the association of two differents lesions: a WT and an extranodal mucosa-associated lymphoid tissue lymphoma.[4] Extranodal marginal zone B-cell lymphoma is probably the most common type of lymphoma truly of salivary gland origin [3] and should be distinguished from nodal lymphomas presenting in intraparotid lymph nodes which usually carry a worse prognosis. [5] Most of cases occur in women, particulary aged over 50, with a history of Sjögren's syndrome or other autoimmune disease. In our case, no history of Sjögren's syndrome or other autoimmune disease was mentioned. Futhermore, the absence of lympho-epithelial lesion is a supplementary argument for the nodal origin of the marginal zone B-cell lymphoma. This finding confirm also WT's histogenesis. Nodal marginal zone B-cell lymphomas arising of intraparotidal Warthin's tumour are real nodal lymphomas and require a thorough staging examination.

References

1. Saxena A., Memauri B, and Hasegawa W. Initial diagnosis of small lymphocytic lymphoma in parotidectomy for Warthin tumour, a rare collision tumour. J Clin Pathol. 2005;58:331-333.

2. Park CK, Manning JT, Battifora H, Medeiros LJ. Follicle center lymphoma and Warthin tumor involving the same anatomic site. Report of two cases and review of the literature. Am J Clin Pathol. 2000;113:113-119.

3. Marioni G, Marchese-Ragona R, Marino F et al. MALT-type lymphoma and Warthin's tumour presenting in the same parotid gland. Acta Otolaryngol. 2004;124:318-323.

4. Isaacson PG, Müller-Hermelink HK, Piris MA et al. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Jaffe ES, Harris NL, Stein H, Vardiman JW eds. WHO Classification Tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press, 2001:157-160.

5. Simpson RHW, Sarsfield PTL. Benign and malignant lymphoid lesions of the salivary glands. Current Diagnostic Pathology. 1997;4:91-99.

We thank the reader for the careful and critical evaluation of our publication “Value of multicolor Fluorescence in situ Hybridization (UroVysionTM) in the differential diagnosis of flat urothelial lesions” published by Stephan Schwarz, Michael Rechenmacher, Tomas Filbeck, Ruth Knuechel, Hagen Blaszyk, Arndt Hartmann and Gero Brockhoff. The reader realized some inconsistency in the Material and Methods section of our paper regarding HER2 immunohistochemistry (IH). In our lab for some purposes a manual IH procedure is performed, for others we execute an automated one. In fact for the study published by Schwarz et al. we used a combination of both: section preparation was done manually and the subsequent staining procedure was performed on the NexES immunostainer (Ventana Medical Systems, Tucson, Arizona, USA). However, we agree with the reader that we produced some inconsistency and incorrectnesses in the Material & Methods. Hence we would like to provide this amended description of immunohistochemical HER2 staining and interpretation as follows:

“HER2 immunostaining was done on 2 mm sections using a HER2 antibody (CB11 CB11-Pathway, prediluted, FDA approved, Ventana Medical Systems, Tucson, Arizona, USA). Before staining, the tissue slides were deparaffinised and rehydrated at room temperature. For antigen retrieval the sections were immersed in 10 mmol/l citrate buffer and microwaved for 30 min using 300 Watt (no pressure cooker was used). Subsequently the sections were cooled by rinsing water for a couple of minutes. Then an automated staining protocol on the NexES immunostainer (Ventana Medical Systems, Tucson, Arizona, USA) was performed featuring some slight modifications with respect to the recommendation given by Ventana (http://www.ventanamed.com/msds/files/14160USb2.pdf). The protocol described here numerously proved to work reliably on the NexES immunostainer. After a 30-minute incubation at 37°C with the primary antibody, sections were incubated for another 10 minutes at 37°C with a secondary biotinylated antibody and then with avidin-peroxidase for another 10 minutes; 3',3-diaminobenzidine was used as the chromogen. All products needed for these steps are included in the DAB detection kit provided by the manufacturer (Ventana Medical Systems, Tucson, Arizona, USA). Slides were haematoxylin counterstained, dehydrated, and mounted. A multiblock control consisting of four cell lines representing different staining intensities ranging from 0 to 3+ (MDA-MB-231: Score 0, MDA-MB-175: Score 1+, MDA-MB-453: Score 2+, and SK-BR-3: Score 3+) served as controls for all specimens.

Again we would like to thank for the careful reading of our manuscript and for coming up with the letter to the editor. This procedure assures appropriate publication quality of JCP.

Gero Brockhoff (correspondence author)