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Squamous Cell Carcinoma

Definition

Malignant neoplasm of the bronchopulmonary epithelium with evidence of either keratinization or intercellular bridging and graded into well, moderately and poorly differentiated on the basis of the amount of keratinization present.

Clinical Features

  • Majority in males
  • Signs of bronchial obstruction:
    • such as:
      • obstructive pneumonitis
      • atelectasis
    • in ≈50%
  • Most centered in segmental bronchi (Fig. 1
    Intraluminal bronchial growth of squamous cell carcinoma.

    Fig. 1: Intraluminal bronchial growth of squamous cell carcinoma.

    ):
    • present as hilar or perihilar masses in chest radiograph
  • May be:
    • peripheral
    • subpleural1,2
  • Larger than other types at diagnosis3

Gross Pathology

  • Tendency to undergo central necrosis with cavitation (Fig. 2
    Large squamous cell carcinoma extending into the pleura and associated with central cavitation.

    Fig. 2: Large squamous cell carcinoma extending into the pleura and associated with central cavitation.

    )
  • Calcification extremely unusual
  • Rarely intrabronchial polypoid mass with only minor extrabronchial spread4

Histopathology

  • Diagnosis of malignancy based on:
    • cell atypia
    • invasiveness
  • Diagnosis of squamous cell type based on detection of:
    • keratin and/or
    • intercellular bridges (Fig. 3
      Microscopic appearance of well-differentiated squamous cell carcinoma.

      Fig. 3: Microscopic appearance of well-differentiated squamous cell carcinoma.

      )
  • Keratin formation may be seen:
    • in isolated cells:
      • isolated necrotic cells should not be confused with keratinized cells
    • more commonly in ‘keratin pearls’
  • Whorl formation and definite stratification of tumor cells:
    • used by some as presumptive evidence of squamous differentiation in absence of features listed:
      • according to WHO classification should be in undifferentiated large cell category
  • May be:
    • oncocytoid appearance of tumor cells:
      • due to increased mitochondrial density
    • giant cell foreign body reaction to keratin
    • palisaded granulomas
    • extensive infiltration by neutrophils and other inflammatory cells:
      • simulating inflammatory malignant fibrous histiocytoma
    • lepidic type of growth into air spaces at tumor periphery5
  • Bronchial mucosa adjacent to tumor:
    • usually squamous metaplasia
    • sometimes carcinoma in situ
    • occasionally extending several centimeters from main mass6
  • Ultrastructurally (Fig. 4
    Squamous cell carcinoma of lung. Neoplastic cells with numerous tonofilaments, some of them attached to desmosomes. This is characteristic of squamous differentiation. (×16,850)

    Fig. 4: Squamous cell carcinoma of lung. Neoplastic cells with numerous tonofilaments, some of them attached to desmosomes. This is characteristic of squamous differentiation. (×16,850)

    ):
    • abundant tonofilaments
    • complex desmosomes
    • basal lamina formation7,8

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Squamous Cell Carcinoma

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Small Cell Carcinoma

  • Product p63:
    • consistently expressed in pulmonary squamous cell carcinoma but not small cell carcinoma
    • potentially useful tool to distinguish these two tumors15

Staging/grading

  • Depending on amount of keratinization graded into:
    • well differentiated
    • moderately differentiated
    • poorly differentiated

Genetics

References

1 Funai K, Yokose T, Ishii G, Araki K, Yoshida J, Nishimura M, et al. Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol. 2003;27:978–984.

2 Tomashefsky JF, Connors AF, Rosenthal ES, Hsiue IL. Peripheral vs. central squamous cell carcinoma of the lung. A comparison of clinical features, histopathology, and survival. Arch Pathol Lab Med. 1990;114:468–474.

3 Bateson EM. The solitary circumscribed bronchogenic carcinoma. A radiological study of 100 cases. Br J Radiol. 1964;37:598–607.

4 Dulmet-Brender E, Jaubert F, Huchon G. Exophytic endobronchial epidermoid carcinoma. Cancer. 1986;57:1358–1364.

5 Kolin A, Hiruki T. Palisading granulomas associated with lung cancer. Arch Pathol Lab Med. 1990;114:697–699.

6 Black H, Ackerman LV. The importance of epidermoid carcinoma in situ in the histogenesis of carcinoma of the lung. Ann Surg. 1952;136:44–55.

7 Dingemans KP, Mooi WJ. Ultrastructure of squamous cell carcinoma of the lung. Part 1. Pathol Annu. 1984;19:249–273.

8 Havenith MG, Dingemans KP, Cleutjens JPM, Wagenaar SS, Bosman FT. Basement membranes in bronchogenic squamous cell carcinoma. An immunohistochemical and ultrastructural study. Ultrastruct Pathol. 1990;14:51–64.

9 Nelson WG, Sun T-T. The 50- and 58-kdalton keratin classes as molecular markers for stratified squamous epithelia. Cell culture studies. J Cell Biol. 1983;97:244–251.

10 Said J. Immunohistochemistry of lung tumors. Lung Biol Health Dis. 1990;44:635–651.

11 Said JW, Nash G, Sassoon AF, Shintaku IP, Banks-Schlegel S. Involucrin in lung tumors. A specific marker for squamous differentiation. Lab Invest. 1983;49:563–568.

12 Bejui-Thivolet F, Liagre N, Chignol MC, Chardonnet Y, Patricot LM. Detection of human papillomavirus DNA in squamous bronchial metaplasia and squamous cell carcinomas of the lung by in situ hybridization using biotinylated probes in paraffin-embedded specimens. Hum Pathol. 1990;21:111–116.

13 Green LK. Basaloid squamous cell carcinoma of the lung: a review of 292 cases (Abstract). Mod Pathol. 2003;16:307a.

14 Moro D, Brichon PY, Brambilla E, Veale D, Labat F, Brambilla C. Basaloid bronchial carcinoma. A histologic group with a poor prognosis. Cancer. 1994;73:2734–2739.

15 Wang BY, Gil J, Kaufman D, Gan L, Kohtz S, Burstein DE. P63 in pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol. 2002;33:921–926.

16 Sozzi G, Pastorini U, Moiraghi L, Tagliabue E, Pezzella F, Ghirelli C, et al. Loss of FHIT function in lung cancer and preinvasive bronchial lesions. Cancer Res. 1998;58:5032–5037.

17 Tomizawa Y, Nakajima T, Kohno T, Saito R, Yamaguchi N, Yokota J. Clinicopathologic significance of Fhit protein expression in stage 1 non-small cell lung carcinoma. Cancer Res. 1998;58:5478–5483.

18 Dosaka-Akita H, Shindoh M, Fujino M, Kinoshita I, Akie K, Katoh M, et al. Abnormal p53 expression in human lung cancer is associated with histologic subtypes and patient smoking history. Am J Clin Pathol. 1994;102:660–664.

19 Zheng J, Shu Q, Li Z-H, Tsao J-I, Weiss LM, Shibata D. Patterns of p53 mutations in squamous cell carcinoma of the lung. Acquisition at a relatively early age. Am J Pathol. 1994;145:1444–1449.

20 Wistuba II, Gazdar AF, Minna JD. Molecular genetics of small cell lung carcinoma. Semin Oncol. 2001;28:3–13.

Last updated: 28 Mar 2006

Squamous Cell Carcinoma

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