ADVNCED CYTOPATHOLOGY MEDS2135

Case study 3: Non-Gynae

Coordinator: Karin Bradshaw

Student Name:

Abdullah Bandar Almutiri

Student Number: 3276950 Date Submitted: 14/05/2013

Introduction The cytology laboratory is considered as one of the most important tool to help in diagnosis of many diseases. Many ancillary tests work as complementary to get a final diagnosis. In this case study of 64 years old female, Respiratory cytology is used to get the precise diagnosis. Which is the study of the cells that exfoliate within the respiratory tract whether they are originating from respiratory system or they belong to a tumor that metastasis to the lung or other parts of the respiratory tract. The use of endoscope to sample cells from the lower portion of respiratory tract lead to an improvement in the result that can be obtained compared to the conventional sputum sample (4). Bronchial wash is mainly dependent on the use of a bronchoscope through washing the mucosa by saline and consequent aspirate of that saline which contains the cells that can be centrifuged and smeared into the slide. By examining the wash return fluid, the doctor can identify any abnormality such as bleeding, fungal infections and different kinds of lung tumor. Patients undergoing bronchial washing usually have mild side effects which include coughing, sore throat and a sleepy feeling from being sedated (4, 8).

Case Report CLINICAL DETAILS Type of specimen: Bronchial washing. Age: 64 years old. Gender: Female. Clinical notes: The patient has a mass in the upper right lobe of the lung.

Material and Method The specimen collected from the upper right lobe of the lung by using bronchoscope technique. Bronchial washing or bronchoscopy is a procedure used to investigate diseases in the lung. During the procedure, the patient is injected with saline into the lung through a fiberoptic bronchoscope (4). The bronchial wash then sucked out and sent to the cytology laboratory for the investigation. Bronchial washings are easily obtained and are useful in diagnosis of many respiratory diseases including the centrally located lesions, but in bronchial washing the cytology must prepare the smear without any delay because the cells in the saline can undergo degenerative changes. One slide was reserved for screening any abnormality. Page 2

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

CASE DESCRIPTION Microscopic description: The smear of bronchial washing is satisfactory, because at low power the smear is hypercellular and containing crowded branching groups Cells present in acinar groups. The smears show abundant ciliated bronchial cells in significant numbers. Macrophages and red blood cell present. The background of the slide is mucoid (Figure 1A, 1B). Bronchial cells (ciliated bronchial cells) are seen in significant numbers in bronchial washing specimens. Columnar shaped cells with cytoplasmic tail present singly and in loosely cohesive groups, basally located nucleus, Round / oval nuclei, Smooth, fire to mildly coarse dark chromatin, Nucleoli is also seen (Figure 1B). Macrophages have round shaped nuclei which are centric or eccentric, finely granular chromatin; some have more nuclei and other bi nuclei, foamy cytoplasm (Figure 1C). Squamous cells present in very few numbers which reflect contamination from the upper respiratory tract in sputum or bronchial washings. Predominately superficial squamous cells (Figure 1D).

Small cell carcinoma: Small cells presents singly and in groups lined up with scant to absent cytoplasm (Figure 2A, 2B). Nuclear molding is prominent, which is feature of small cell carcinoma (Figure 2C, 2D).

A high N\C ratio. Small cell nuclear staining ranges from dark to pale. Hyperchromatic, Nucleoli is invisible (Figure 2A, 2D). In the cropped image of C (Figure 2D) it show elongated groupings of small cell with Scant cytoplasm or absent cytoplasm and irregular moulded nuclei; dark chromatin, inconspicuous nucleoli; very high N\C ratios.

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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Figure 1. A At low power the smear is hypercellular and containing crowded branching groups Cells with mucoid background Pap stain x20. B Shows bronchial cells with cilia Pap stain x20. C Macrophages and other material are present in the background Pap stain x20. D Squamous cells present in very few numbers Pap stain x20.

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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Figure 2. A Small cell carcinoma presents singly and in groups Pap stains x40. B small cell carcinoma seen in a linear Pap stain x20. C The molding of nuclei around each other; which is feature of small cell carcinoma Pap stain x40. D cropped image of C to show the molding, PAP stain.

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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DIAGNOSIS AND RECOMMENDATION Diagnosis: Bronchial washing/ Malignant cells present (Small cell carcinoma). Recommendation: Referral for oncologist; chemotherapy or combination chemotherapy with concurrent chest radiotherapy (RT) for treatment (9, 10).

DISCUSSION
Small-cell carcinoma Small cell lung cancer (SCLC) is a malignant cancer which is most commonly arises inside the lung, commonly called Small cell carcinoma. This tumor usually occurs centrally and metastasizes very early to the hilary lymph nodes, bones, brain, and liver. Also it can infrequently happen in other body sites, like for example the gastrointestinal tract and prostate in man. When SCLC infects the lung, it is sometimes called "oat cell carcinoma" due to the scanty cytoplasm and flat cell shape (6). In the cytology definition of the small cell carcinoma characteristics is small cells with finely granular nuclear chromatin and not easily seen nucleoli, scant cytoplasm. There are a high mitotic count and nuclear molding (7). Small cell carcinomas are smaller than normal cells, and the primary stage of this cancer is too difficult to diagnose because the cell is too small and difficult to find. Small cell carcinoma belongs to a group of tumors know as (bronchial neuroendocrine tumors). As they arise from neuroendocrine cells in the bronchus. Neuroendocrine cells found throughout the body and they release hormones when they stimulate by neural stimulus (1, 6). Pulmonary neuroendocrine cells involved in the regulation of oxygen levels. By detecting increase oxygen or increased carbon dioxide levels and sending chemical message to help the lung adjust to these changes. The people who living at high altitudes, where oxygen levels are lower, have a higher number of neuroendocrine cells in their lungs.

The main cause of small cell cancer is tobacco smoking and the majority of patients how infected have strong smoking history of all histological types of lung cancer, Squamous cell carcinoma and SCLC have the strongest relationship to tobacco. Approximately 98% of patients with SCLC have a smoking history. Patients with SCLC should be encouraged to stop smoking, as smoking cessation is associated with improved survival (6).

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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DIFFRENTIAL DIAGNOSIS Problems in diagnosis are to differentia between small cell and poorly differentiated non-small cell carcinomas and a tendency to include tumors with larger than expected nuclei in the nonsmall cell category. In general, if the nuclear features of a problematical tumor are those of small cell carcinoma- that is, granular chromatin without prominent nucleoli- the neoplasm will fall into the small cell carcinoma group Histologically; vesicular nuclei with prominent nucleoli would generally be evidence of non-small cell tumor. Also, immunocytochemistry is also helpful in differentiating between non- small cell lung cancer and small cell; small cell carcinomas are reactive with CD 56, and other neurondocrine markers, whereas non-small cell carcinomas are generally unreactive(2, 3). In addition, it is sometimes very difficult to distinguish small cell carcinoma from lymphomas, particularly those of follicular center cell origin with pronounced cell polymorphism and nuclear irregularity. Cell dispersal together with a rim or tail of intact cytoplasm in individual cells and a background of round, cytoplasmic fragments staining blue with MGG (lymphoid globules\ lymph glandular bodies) are helpful features in making a diagnosis of lymphoma. Dispersed cells of small cell carcinoma are usually bare nuclei. Some low-grade lymphomas can show pseudomoulding due to clustering of the nuclei. However, significant true nuclear moulding is not seen in lymphoma and cytoplasm is usually maintain while, small cell carcinoma usually do not maintain cytoplasm (2, 9). Furthermore, Reserve cell hyperplasia. Reserve cells are rarely seen except in reactive states. They are small in size (compare the size with adjacent columnar cell), have hyperchromatic nuclei, and may show evidence of nuclear molding. It is important not to confuse them with small cell carcinoma. TREATMENT and PROGNOSIS Treatment Treatment options depend on factors such as stage of the cancer, the position of the tumor, and patients fitness to tolerate the therapy. There are two stages of small cell carcinoma that is usually determined by the presence or absence of metastases which are extensive stage (ES) and including limited stage (LS). In cases of LS-small cell carcinoma, combination chemotherapy is administered together with concurrent chest radiotherapy (RT) for treatment. Generally, Small cell carcinoma spreads very quickly throughout out the body and patients do not benefit from surgery. Chemotherapy is the main treatment is given to patients with extensive disease, to prolong their life and relieve their symptoms (5, 10).

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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Prognosis Lung cancer has one of the worst survival outcomes of any cancer. The outcome is dependent on the stage and type of lung cancer. Overall, for all types of lung cancers irrespective of the stage at the time when the cancer is diagnosis, only 25% of patients will live for one year and 8% will live for five years. For small cell lung cancer the Surviving for five years is 1% for stage 4. Indicators of poor diagnosis include relapsed disease, weight loss, and poor performance status (5, 10). For all patients with SCLC, activity should be encouraged and a dietary consultation should be obtained. SUMMARY The patient is 64 years old, Female that has a mass in the upper right lobe of the lung the specimen collected by using bronchoscope technique. One slide was reserved for screening any abnormality. This case is reported as Malignant cells present (Small cell carcinoma) as there is indication of abnormality. Chemotherapy is the main treatment for this patient when considering his age as well, to prolong their life and relieve their symptoms.

Small cell carcinoma is highly aggressive as it usually characterized by aggressive actions, fast growth, early spread to other sites in the body organs, exquisite sensitivity to chemotherapy and radiation the survival rate is always low. Therefore advice to avoid the risk factors for development of disease such as smoking because smoking is the main cause of lung cancer, the only means of decreasing the occurrence of this disease as well as that of small cell carcinoma specifically, is to decrease the occurrence of smoking. Furthermore, development of highly advanced early diagnostic facilities and increase public awareness of the effects of smoking should be the main primary concern of medical centers and government.

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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REFERENCES

1. Stuff.com. c. Gyn Atlas Section 4c. Copyright 2013 Hologic, Inc. All Rights Reserved; 2013; Available from: http://www.cytologystuff.com/study/section4c.htm#squamous. 2. Ducztman BSD, Edmund S. Cibas. Cytology Diagnostic Principle and Clinical Correlates. Saunders: Linda Belfus; 2009. 3. Marluce Bibbo DW. Comprehensive Cytopathology. SAUNDERS2008. 4. Collins W. Bronchial Washing Procedures. 2013; Available from: http://www.livestrong.com/article/161434-bronchial-washing-procedures/. 5. Austin JHM, Yip R, D'Souza BM, Yankelevitz DF, Henschke CI. Small-cell carcinoma of the lung detected by CT screening: Stage distribution and curability. Lung Cancer. 2012;76(3):339-43. 6. Behded Shambayati. CYTOPATHOLOGY. United States: Oxford University Press; 2011. 7. DeMay RM. The pap test: Chicago : ASCP Press c2005 . 8. Fernndez-Villar A, Gonzlez A, Leiro V, Represas C, Isabel Botana M, Blanco P, et al. Effect of Different Bronchial Washing Sequences on Diagnostic Yield in Endoscopically Visible Lung Cancer. Archivos de Bronconeumologa ((English Edition)). 2006;42(6):278-82. 9. Kocjan WGWG. Diagnostic cytopathology. 3rd ed: Edinburgh : Churchill Livingstone/Elsevier; 2010. 10. Sun J-M, Ahn M-J, Ahn JS, Um S-W, Kim H, Kim HK, et al. Chemotherapy for pulmonary large cell neuroendocrine carcinoma: Similar to that for small cell lung cancer or non-small cell lung cancer? Lung Cancer. 2012;77(2):365-70.

Student Name: Abdullah Bandar Almutiri, Student Number: 3276950

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